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CV lecture one

1.) Electrophysiology
a. Action potentials & conduction velocity differs within the heart
b. Compared to other tissues the heart has a relatively long AP and Refractory period
2.) Phase zero, the upstroke of the action potential is: ( see graph on page 3)
a. Relatively fast in Atrial myocytes, Ventricular myocytes, and conduction fibers
b. Relatively slow in SA & AV node
i. This is essential for ventricular filling
3.) Membrane potentials
a. Na & Ca are in higher concentration outside the cell & K is higher in the cell
b. Phase 4:
i. Ventricles, Atria, & His-Purkinje system
Stable Resting membrane potential (-90 mv)
Potential is determined by K, which has the highest conductance
Na plays a minor role, because it is not very permeable
Current is Ik1
c. Phase 0 the Upstroke
i. Transient increase in Na conductance=> Na influx
d. Phase 1
i. Transient repolarization
ii. due to (1) decreased Na conductance ( inactivation gates are closing) and (2) the concentration and charge
gradients favor K outflow
e. Phase 2
i. Plateau
ii. Due to increase in Ca conductance & decrease K conductance
L type Ca channels
iii. These forces oppose each other
f. Phase 3
i. Repolarization
ii. Ca conduction decreases & K increases
iii. Outward Ik repolarizes the cell
4.) Slow response (SA & AV)
a. Phase 4 in SA & AV nodal cells
Resting membrane is not stable (max is -65mv)
Ik1 is very low or absent
If , a Na current, is responsible for the spontaneous depolarization ( automaticity) of the SA node
If is turned on by repolarization ensuring that a new AP is always generated
b. Phase 0
i. is due to a Ca current, not Na
T-type Ca Channels
ii. not as rapid or sharp as in other cardiac tissue
c. Phase 1 & 2 are absent
d. Phase 3 due to outward K current
5.) Conduction velocity trend: Purkinje > ventriclesatria> SA AV
a. Conduction velocity depends on the size of the inward current during the AP upstroke & cable properties
b. Length of the AP does not matter
6.) Frequency of firing
a. SA>AV>His-Purkinje
7.) Activation Sequence of Heart
a. SA=> Left and Right atria via intermodal tracts=>AV node=>Bundle of His=>Purkinje systems
8.) The SA normally serves as the pace maker
a. AV node & His-Purkinje are latent pace makers
b. The fastest rate of phase four depolarization determines what myocardial component will act as the pace maker
c. Under normal circumstances: fastest-SA>AV> His-Purkinje-slowest
d. Ways to change pace maker activity
i. Alter (1) phase four rate of depolarization (2) max negativity of phase four (3) threshold potential
ii. Lecture Examples:
Sympathetic Stimulation increases SA phase 4 depolarization
Parasympathetic (vagal) stimulation decreases SA phase 4 depolarization
Drugs can decrease SA depolarization, by increasing the threshold potential ( see graph pg 10)
a. Ex: Quinidine
A reduction of Ca current in slow response cells can also influence automaticity (graph pg 15)


Normally the Ca current is activated at the end of phase 4 depolarization and accelerated
the rate of diastolic depolarization
Decreases in extracellular Ca or use of Ca antagonist decreases the amplitude and slope
of the slow diastolic depolarization in the SA node

9.) Factors affecting AP

a. Amplitude, Rate of change ( dVm/dt) phase 0, Resting membrane potential
10.) Lecture Examples AP
a. Timing of AP
i. APs that occur too early (A) will induce very small nonpropagated responses. APs that occur early (B) in
the relative refractory period have smaller amplitudes and les steep upstroke slopes than those occurring
later in the refractory period. The conduction of APs early in the refractory period is also relatively slow. If
conduction is too slow=> conduction block. (see graph pg 8)
b. Tetrodotoxin blocks Na channels (see graph of bottom on pg 11)
Decreases the amplitude & rate of rise of AP by decreasing Na current
Additionally the notch, which represents Ito, the transient outward K current during phase 1
repolarization one decreases and eventually disappears with higher doses on Tetrodotoxin
transforms fast AP (purkinje) into a slow AP (SA)
c. Increase in extracelluar K concentration (see graph of bottom on pg 12, pg 300 of book)
i. Occurs in patients with coronary artery disease
Diminished blood flow to the myocardium results in reduced Na-K pump activity=>
intracellular Na and extracelluar K
ii. Graph A is normal
iii. B-E:
As extracelluar K is increased=> less polarized membrane potential=> easer to reach threshold
As a result amplitude, duration, and steepness of the APs all diminish=> decreased conduction
In Graph D & E the membrane voltage reaches the point were all fast Na channels are
inactivated=>cell behaves as slow response cell
d. L type Ca Channels
i. Norepinephrine, increases Ca conductance during the plateau (sympathetic)
ii. ACH decreases Ca conductance during plateau (parasympathetic)
iii. Enhancement of Ca influx through L type receptors by isoproterenol (graph pg13)
L is for long lasting, these channels open during the upstroke at about -20mV and stay open
throughout the plateau
iv. Ca channel antagonist (see graph pg 14)
verapmil, amlodipine, & diltiazem
Decrease ca current=> diminish length of plateau=> decreased myocardiac contraction force
11.) Relationship btwen CV and AP
a. Conduction velocity along the fiber varies with the amplitude of to AP and the rate of change of the potential
(dVm/dt) during phase 0. The amplitude of the AP = the potential difference between the fully depolarized and fully
polarized regions of the cell interior.
Cardiac glycosides inhibit the Na-K pump=> intracellular accumulation of Na=> decreases the activity of the Ca/Na exchange pump
CV 2 Electrocardiography
EKG = electrocardiogram (ECG or EKG)
Measures the sum of all electrical forces at the level of the persons skin using electrodes
Direction and magnitude of the deflections on the EKG depend on how the electrical forces are
aligned with respect to a set of specific reference axes
Electrical current flows from negative to positive charge
Upward wave = current flowing towards the positive end of the skin electrode
Downward wave = current flowing away from the positive end (twds neg end) of skin electrode
Current Vectors:
o When current is flowing parallel in the same direction as the lead max pos. increase on
o When current is flowing parallel in the opposite direction of the lead max neg. increase on
o When current is flowing at an angle toward the positive end of the lead some positive
increase on EKG

When current is flowing at an angle away from the positive end of the EKG some negative
decrease on EKG
o When current is flowing perpendicular to lead flat line
o When there is no current flat line
EKG Leads 12 total leads, 6 on limbs and 6 on chest (precordial
6 limb leads:
o 3 standard or bipolar (have a positive and negative
Lead I = R arm to L arm
Lead II = R arm to L leg
Lead III = L arm to L leg
o 3 augmented or unipolar (have only a positive direction)
aVR = from body wall twds R arm
aVL = from body wall twds L arm
aVF = from body wall twds L foot
o the limb leads only detect cardiac vectors on the frontal
plane of the body
o the normal average mean electrical axis is approximately +60
o the magnitude of the deflection reflects how parallel the electrical force is to the axis of the
lead being examined
6 chest/precordial leads: all unipolar (have only a positive
o From R to L: V1, V2 (straight down), V3, V4, V5, V6
(straight towards L side of body)
o V1 and V2 = record mainly electrical activity of right
o V3 and V4 = record mainly electrical activity of the
o V5 and V6 = record mainly electrical activity of the left
o The chest leads detect cardiac activity in a horizontal plane
Electrical Conduction
Normal beat starts at the SA node (junction of RA and SVC)
Electrical propagation through the heart: SA node atria AV node common bundle bundle
branches Purkinje fibers ventricles
o Reflected by 3 major deflections on the EKG P wave, QRS complex, and T wave
o SA and AV node have slow response
o Repolarization of the atria are hidden in QRS during depolarization of ventricles (dont see it)
P wave = atrial depolarization
QRS complex = ventricular depolarization
T wave = ventricular repolarization

EKG on frontal plane

Vector Direction (frontal
1) impulse origin and atrial depolarization
P wave
2) septal depolarization
Q wave
3) apical and early ventricular depolarization
R wave
4) late ventricular depolarization
S wave
5) repolarization
T wave
EKG on the horizontal plane
o QRS is mainly negative in V1 and positive in V6
o V3 and V4 are isoelectric transition electrodes the up and down portions of the QRS are
Interpreting the EKG
Paper moves at a constant speed of 25mm/sec
Thick lines occur every 5mm, thin lines occur every 1mm
X-axis is time 5 large boxes = 1 sec (1 large box = .2sec, 1 small box = .04sec)

Y-axis is voltage 1.0mV produces a deflection of 10mm (each small box represents .10mV and
each large box is .5mV)
EKG Analysis
1) Voltage calibration
In some cases of hypertrophy or bundle branch blocks, QRS complexes are larger than normal
recording is made at standard voltage 1.0mV = 1 large box (instead of normally where 1.0mV
= 2 large boxes)
2) Rhythm
Normal rhythm is called the SINUS RHYTHM, which has 4 components:
o Every P wave is followed by a QRS complex
o Every QRS complex is preceded by a P wave
o The P wave is upright in leads I, II, and III
o The PR interval is greater than 0.12sec (three small boxes)
3) Rate
Normal rate is between 60-100 beats/min
There are three methods for calculating rate
o Count the number of mm between 2 consecutive QRS complexes to use the equation:

Memorize the value that corresponds to HR of each sequential large box after the first QRS
1st = 300, 2nd = 150, 3rd = 100, 4th = 75, 5th = 60, 6th = 50 (use this to estimate the
HR depending on where the next QRS peak is)
o Count the number of QRS sequences between a 3 second interval and multiply by 20
This is particularly useful for determining irregular HR
4) Intervals (PR, QRS, QT)
PR = from the beginning to P to the beginning of Q (normal = 0.12-0.2 sec)
QRS = from beginning of Q to end of S (normal < 0.1 sec)
QT = from beginning of Q to the end of T (normal = 0.3-0.4 sec)
5) Mean QRS Axis
EKG represents the average electrical activity
QRS axis is usually -30 to +90
QRS axis is primarily upwards in leads I and II
o If it is not, the axis is abnormal (not +60) and should be determined from the limb leads by
finding the most isoelectric limb lead, then looking at the lead perpendicular to it the
mean axis points to the positive pole of that lead if it is a +QRS
6) Abnormalities
Look for variance in voltage, rhythm, rate, interval durations, and axis and combine with variances
in shape of the wave forms
Atrial Enlargement
o RA enlargement P wave has double bump with left side of bump (which
represents the RA) larger than the right side (represents the LA)
o LA enlargement P wave had double bump with right side of bump larger
than left side
Sinus Bradycardia APs originate at SA at slow pace slowing of HR
o All complexes are normal and evenly spaced but the rate is <60bpm
Sinus Tachycardia APs originate at SA at fast pace rapid HR
o All complexes are normal and evenly spaced but the rat is >100bpm
Wandering Atrial Pacemaker impulses orginate from varying points in atria
o Variation in P wave contour, PR intervals, PP and thus RR intervals, normal QRS and T

Wolff-Parkinson-White (preexcitation) Syndrome impulses originate at SA node and preexcite

peripheral conduction system and ventricular muscle via bundle of Kent without delay at the AV


After normal delay at AV node, also get impulses via regular route double depolarization
P wave is immediately followed by short delta wave, producing slurred upstroke on wide QRS
w/short or no PR interval

First-Degree Heart Block fixed but prolonged PR interval

o P wave precedes each QRS complex, PR interval is uniform but >0.2sec

Second-Degree Heart Block (Mobitz 1/Wenckebach) progressive worsening of PR interval with

intermittent dropped beats
o Starts with good rapid conduction across the crest of the AV node and normal PR intervals
conduction gets worse and PR gets longer until conduction fails and QRS is dropped, then
the AV node recovers and PR goes back to normal (continuous cycles of this)

Third-Degree (complete) AV Block no relationship between P and QRS, ARS rate slower than P rate
o Impulses orginate at SA node and below the AV node block
o Junctional Rhythm atria and ventricles depolarize independently, QRS less frequent,
regular at 40-55/min but normal in shape

Idioventrical Rhythm atria and ventricles depolarize independently, QRS less frequent,
regular at 20-40/min but with wide and abnormal shape

AV dissociation no relationship between P and QRS QRS is faster than P

o slower supraventricular rhythm and rapid ventricular rhythm P waves less frequent than
QRS and totally unrelated

Bundle Branch Blocks

o R ventricular block extra vector of depolarization on the R side (R), wide QRS, longer time

L ventricular block extra vector of depolarization on the L side (R), widening of QRS and R

*when reading an EKG, find the most isoelectric lead and use the one perpendicular to it to get your info!

Cardiac Cycle CV Lecture 3


Cardiac Cycle is composed of two parts (more in IV)

A) Diastole: relaxation and filling of the heart
B) Systole: contraction and emptying of the heart

II) The heart has four separated chambers

A) Two atria
B) Two ventricles
C) Valves prevent back flow of blood
1) Atrium separated from ventricle by an atrioventricular valve
(a) Right = tricuspid valve
(b) Left = mitral (aka bicuspid) valve
2) Ventricle separated from arteries by semilunar valves
III) Right side of heart
A) Blood from venae cavae to the right atrium
B) From right atrium through the tricuspid to the right ventricle
C) Right ventricle through the semilunar valve to the pulmonary artery
D) Same deal on left side, with different names of valves
venae cavae right atrium (tricuspid valve) right ventricle (semilunar valve)

pulmonary artery

Blood Flow Through the Heart


aortic semilunar valve left ventricle (mitral valve) left atrium pulmonary vein
IV) Cardiac cycle and Electrocardiograms
A) Diastole
1) Isovolumetric relaxation
Looks like end of systole, but actually beginning of diastole
(b) Semilunar valves and AV valves closed
(i) Pressure in ventricles is higher than pressure in atria
(ii) Pressure in ventricles is lower than pressure in aorta
(iii) Aorta > Ventricle > Atria
(c) No volume change
(d) Pressure starts to decrease in ventricle
(e) Transient increase in atrial pressure = dicrotic notch, imp. to blood pressure measurement
2) Passive filling
(a) Atria start to fill with blood from venae cavae
(i) Pressure increases a little
(ii) AV valves open
(iii) Rapid filling of ventricles
(b) Both atria and ventricles are relaxed
(i) Blood is filling in the atria
(ii) Blood is also entering the ventricle through the open AV valve, reduced filling
(c) Pressure in left atria slightly higher than in left ventricle
(d) Volume rises in the ventricle
3) Atrial Contraction
(a) End of Diastole = Atrial depolarization
(b) SA node fires action potential

(i) Depolarization and contraction of atria

(ii) P wave
(c) Atria contract and send more blood to ventricles, end filling increase in ventricular volume
4) Three phases of filling: rapid, reduced, end
(a) filling of ventricles depends on frequency of contraction (because it occurs during diastole)
(b) increasing frequency of contraction (heart rate) gives same end diastolic volume
(i) decrease volume in ventricles if heart of >200 beats per minute
(ii) athletes have a lower heart rate because contraction is more forceful still sending same
amount of blood
B) Systole
1) Isovolumetric contraction
(a) Wave of depolarization travels
(i) Delay at AV node
(ii) Travels through conduction system
(b) Ventricular contraction
(i) QRS complex = depolarization of ventricles
(ii) Pressure increase in ventricles
Ventricle pressure higher than atrial pressure
Atrioventricular valves close (prevent back flow)
Pressure has not reached/surpassed pressure in the aorta
(iii) Volume stays the same end diastolic volume still
2) Ventricular ejection
(a) Pressure in ventricle surpasses pressure in aorta
(i) Semilunar valves open, blood enters aorta
(ii) Volume in ventricle decreases
(b) Ventricles repolarize T wave No further contraction
(i) Pressure in ventricle falls
(ii) Semilunar valves close, prevents backflow to ventricles
(c) Maximum ejection of blood
(i) End diastolic volume remains in ventricles
(ii) End systolic volume End diastolic volume = stroke volume
(iii) 135 ml 65 ml = 70 ml ejected with each contraction
3) P wave atrial depolarization, QRS complex ventricular depolarization, T wave ventricular
repolarization (U waves, not always seen, may represent repolarization of Purkinje Fibers,
prominent in hypokalemia)
Basically, look at and understand slide 5: events of the cardiac cycle. A comparable picture can be found on p.
149 of Costanzos Physiology (3rd ed.) with explanations from p. 148 -151
Cardiovascular System Lecture 4: Hemodynamics and Flows

Velocity, Flow and Cross-sectional Area

a. the cardiovascular system is arranged in series and parallel circuits
b. the cardiovascular system attempts to maintain constant flow
i. velocity will vary inversely with cross sectional area


cross-sectional area is greatest in capillaries followed by venules/veins

velocity decreases as cross-sectional area increases
i. though the cross sectional area is greatest in the capillaries, the largest drop in pressure occurs between the
arteries and arterioles
1. this is because there are far more capillaries arranged in parallel than arterioles, and thus the total
resistance is much less for capillariesthis concept will be explored shortly
since the cross-sectional area increases as we proceed through the circulatory system (from aorta to arteries to
arterioles to capillaries), velocity decreases



Relationship between Velocity and Pressure

a. total pressure = lateral pressure + dynamic(or kinetic) pressure
b. effect of velocity on dynamic component of pressure can be estimated from the eqn.:
i. in most arterial locations, the dynamic pressure will be a negligible fraction of total pressure
ii. at sites of constriction/obstruction, dynamic pressure may increase significantly
c. pressure falls linearly with length along the tube (vessel)
d. lateral pressure will decrease in areas where velocity increases, i.e., lateral pressure in narrow sections will be less
than the lateral pressure in wider sections
Relationship between Pressure and Flow
a. Poiseuilles Law: applies to steady laminar flow of newtonian fluids
i. N.B. not ACTUALLY applicable to CV system, because flow is pulsatile, vessels are not rigid cylinders,
and blood is not newtonian
b. Poiseuilles Law describes the flow of fluids through tubes in terms of flow, pressure, dimensions of tube, and
viscosity of liquid
c. Equation:
Q = (Pi Po) r4 / 8l



flow through the tube will increase as pressure gradient is increased; flow will decrease as either viscosity or length
increases; radius is critical because it is raised to 4th power; flow is directly proportional to radius
at this point, his lecture goes into a number of slides indicating many of the relationships indicated above; basically,
understand the equation and how changing any of the variables will affect the others

Resistance to Flow
a. similar to Ohms Law for electrical circuits: R= E / I
b. for fluid dynamics:
R = Pi Po / Q = 8l / r4
c. vessel diameter is principal determinant of resistance
i. this makes sense, since the resistance will be inversely proportional to the radius to the 4 th power; other
factors will not have such a major effect
ii. arterial occlusion has a large effect on flow: if the radius of an artery (with P=120mmHg) is decreased by
20%, flow will drop from 100ml/min to 41ml/min and it will take a P=293mmHg to restore normal flow
d. Total resistance in a series arrangement equals the sum of individual resistances
i. Rt = R1 + R2 + R3 +
e. Total resistance in a parallel arrangement equals the sum of reciprocals of individual resistances:
i. 1/ Rt = 1/ R1 + 1/ R2 + 1/ R3 +
f. thus, total resistance in parallel arrangement will be less than similar resistance in series arrangements
g. Advantages to parallel arrangement of resistors:
i. can regulate flow to certain destinations
ii. total resistance is less than the resistance of any one resistor
iii. impact of changes in resistance of a few vascular beds on blood pressure is minimized
iv. optimizes gas and substrate distribution dynamics
Laminar Flow and Turbulence
a. turbulent flow occurs when fluid does not flow in definite laminae (layers), but rapid mixing occurs (this will
happen in blood)
b. in turbulent flow, the pressure drop is approximately proportional to the square of flow rate (compared to first order
in laminar flow)
i. i.e., a heart will have to pump harder if turbulent flow develops
c. laminar vs. turbulent flow is determined by the Reynolds number NR using the following equation:
NR = Dv/


d. NR < 2000, flow is laminar

e. 3000 > NR > 2000, flow is transitional
f. NR > 3000, flow is turbulent
Apparent Viscosity of Blood
a. viscosity may vary considerably as a function of dimension and flow
b. apparent viscosity is used as a derived value of blood viscosity obtained under particular conditions
c. apparent viscosity varies as a function of hematocrit


apparent viscosity increases exponentially as hematocrit rises

Physiology Cardiovascular Lecture 5: Arterial Blood Pressure

Arterial Blood Pressure:
Small diameter vessels have a high resistance (ex. Arterioles).
Blood pressure drops a lot at the level of the arterioles.
Elasticity the ability of the blood vessels to deform under stress and then recoil back to their original shape.
Large arteries have high elasticity (lots of elastin fibers in the walls) makes them very efficient hydraulic filters.
o Reduces the workload of the heart
o With old age elasticity and work load of the heart .
Hydraulic filtering and Work:
A. Continuous pump = constant Pressure (P) and Flow (Q)
B. Intermittent pump with rigid tube = larger increase in P and Q with opening and closing of pump. This system works
harder and P .
C. Intermittent pump with Compliant walls = Constant P and Q
o Energy is stored in the wall of the tube allows for constant P and Q, outflow doesnt change.
o This is like our circulatory system but b/w B + C, because our arteries are not infinitely distensible.
Arteries as Pressure Reservoir:
Systole ventricular contraction part of the energy is used to distend arteries, and part to expel blood into aorta.

Diastole ventricular filling pressure in the aorta moves blood back towards ventricles, but it is stopped by the semilunar
o Dichrotic notch aortic valve closure produces a brief period of retrograde flow from aorta back to the valve, there
is a slight decrease in aortic P which creates this extra hump.
Loss of Elasticity in Arteries:
Systole the volume of blood equal to the entire stroke volume must flow through capillaries but, if no distension in
o When arteries are rigid, none of the SV can be stored in the arteries, walls are not compliant.
Diastole flow through the capillaries stops during diastole rigid arteries cant recoil appreciably cant keep constant
flow intermittent flow results.
Low hydraulic filtering requires more energy.
Increased Energy requirement in a Rigid Conduit:
o More energy and O2 is required in a rigid (low hydraulic filter) system plastic tubing vs. native aorta.
Compliance (C, capacitance) describes the volume of blood the vessel can hold at a given pressure.
o Compliance is related to distensibility.
o C = V/P
o Veins are the most compliant can hold the largest volume of blood at low pressure (unstressed volume)
o Arteries much lower compliance, hold much less blood and at higher pressures (stressed volume), most elastic.
o in compliance of veins causes redistribution of blood b/w veins (unstressed volume) and arteries (stressed
o Compliance of arteries as age walls become stiffer, less distensible, less compliant, hold less blood at any
given arterial pressure.
Elastance is the tendency of arterial walls to recoil.
Elastance = P/ (D/D)
o D = max amount aorta distends, D = diameter
Elastance 1/Compliance (opposites).
Elastance is greatest in arteries, smallest in veins.
More elastic tissue leads to more elastic recoil.
Mean Arterial Pressure, Pa
Pulse pressure = Systolic pressure Diastolic pressure
o If all other factors are equal, magnitude of pulse pressure reflects Stroke Volume (volume of blood ejected from L
ventricle on a single beat)
o Largest pressure drop is at the level of the arterioles.
o Pressure greatest in aorta, and decreases steadily to veins (lowest pressure)
o Mean Pressure integral of Aortic P
Pa = Pd (diastolic P) + 1/3 Pulse Pressure

More weight is given to diastolic P because more time spent in this state.
Factors that Determine Arterial BP
Physiological Factors 1) CO (HR x SV), 2) Peripheral Resistance
Physical Factors Arterial blood volume, Arterial compliance
o Physiological factors modify physical ones, both modify arterial BP
1) Increasing CO increases BP
o If instantaneously, Q doubles CO (b/c SV and HR), but P hasnt yet.
o As reach steady-state, P to maintain constant flow
Recall: Q = P/R
o As CO, rate of in BP is lower in younger adults arteries are more distensible and more compliant.
2) Increasing Peripheral resistance increases BP
o If resistance in arterioles (by diameter), initial response is to flow, but get a build up of blood in the system, so
BP to push more blood through arteries and maintain constant flow therefore P.
Arterial Pulse pressure:
stroke volume

CO, Peripheral Resistance MEAN ARTERIAL PRESSURE

SV change in arterial volume, and arterial compliance PULSE PRESSURE (systolic P diastolic P)
1) SV in Pulse Pressure
a. compliance stays constant C = V/P, more energy stored, but no overall change.
b. BUTif low compliance (old age), a V will cause a much greater increase in PP.
2) Total Peripheral Resistance preferentially Systolic Pressure
a. Systolic P a lot more than diastolic P with in TPR b/c of in Compliance HYPERTENSION.
3) Compliance Pulse Pressure
a. lower compliance = syst. P a lot, diastolic P a little PP a lot
b. high compliance = pulse pressure very small
c. ARTERIOSCLEROSIS diameter of arteries, PP
4) Systolic Pressure as move further from heart
a. as move further/lower from heart due to distance and time travel of P wave, BP.
b. In ankle, see small deflection in P wave b/c blood being deflected back towards heart.
Measuring Arterial BP
Constrict artery (usually brachial) block flow of blood
o 1st sound as release air Korotkoff sound, ~ 120mmHg Systolic P
o last sound ~80mmHg Diastolic P
o Korotkoff sound turbulence of flow through small opening, meeting static column of blood causes the noise.
Physiology CV6-Regulation of Arterial Blood Pressure
Determinants of Blood Pressure:
Mean arterial pressure depends on cardiac output, and total peripheral resistance
Cardiac output=Hear Rate x Stroke Volume (CO=HRxSV)
CV6 is all about how these are controlled by our body, either via intrinsic or extrinsic mechanisms to control blood pressure
under different circumstances.
o Extrinsic: affects CO and TPR
o Intrinsic: affects TPR at local level
Mechanisms of extrinsic control from fastest to slowest:
Baroreceptors which mediate vascular reflex(NS control, PNS, SNS)
Chemoreceptors (peripheral and central)
Cardiopulmanory receptors

Humoral receptors (slowest, sometimes trigger effects via gene expression)

Located in the aortic arch and bifurcation of the carotid artery.
Sense STRECH in the aortic arch and carotids due to increased pressure. Do not directly sense pressure, and relay this
information through the vagus nerve.
Sinus nerve from carotid sinus joins the glossopharangeal nerve, which is the ninth cranial pair.
Firing rate is proportional to strech. Therefore with high strech caused by high blood pressure the baroreceptors will fire more
frequently, and less frequently with low blood pressure.
Baroreceptors adapt to circumstances. During chronic hypertension, baroreceptors adapt and change their set point, so
normal firing rate is at higher than normal blood pressure. The baroreceptor reflex effectiveness is lost with chronic
Chemoreceptors: primarily involved in breathing control
Peripheral: in aortic arch and bifurcation of carotids. Stimulated by a decrease in pO2, increase in pCO2, and decrease in pH
o Primary: Causes an (sympathetic) arteriolar vasoconstriction in skeletal muscle, renal, and splanchnic vascular beds.
Also a transient parasympathetic lowering of heart rate.
o Secondary: increased ventilation, which independently decreases parasympathetic stimulation to the heart, resulting
in an increased heart rate
Central: in medualla itself. Sensitive to pCO2 and pH. When flow to the brain decreases CO2 and pH increase. This causes
sympathetic stimulation to many vascular beds and increases TPR. This redirects blood flow to the brain and increases
arteriolar blood pressure which can be dangerous.
In close association with baroreceptors because they travel to the CNS via the same nerves (Vagus nerve, X)
The meduallary cardiovascular center is made up from input from the glossopharangeal nerve, and the vagus nerve which end in
the nuclei tractus solitarius (NTS) in the posterior part of the medulla along with other nuclei here such as the dorsal motor nucleus of
the vagus nerve, and the nucleus ambiguous from the ninth and tenth cranial nerves.
Cardio Inhibitory area-made up of nucleus tractus solitarius (which is made up of the dorsal motor nucleus of the vagus and
nucleus ambiguous)
Vasomotor area-in anterior part of medulla
Cardiac accelerator
In the case of increased blood pressure, the bodys reflex is to decrease blood pressure. This is a baroreceptor reflex.
BaroreceptorNTSvasomotor areainhibit C1 and A1 cells, inhibit cardiac accelerator (slows HR by inhibiting SNS)
C1 causes vasoconstriction through the SNS (Preganglionic ACh, postganglionic NE)
At the same time, parasympathetic activity is stimulated by the nucleus ambiguous and the dorsal motor nucleus of the vagus, further
reducing HR.
With an increase in blood pressure, baroreceptors from the aortic arch fire closer to the end of systole.
Sympathetic Nervous System Effects
Vasodialation of skeletal muscle increases oxygen supply
Preganglionic ACh release to muscarinic receptors on adrenal medulla causes EPI release. EPI binds to beta-1 receptors on
blood vessels and causes vasodialation.
NE also released from adrenal gland in smaller proportions
2 sympathetic inputs to skeletal muscle to cause vasodialation
o SNS releases ACh and NE
o Adrenal Medulla releases EPI into circulation
Parasympatetic nervous system effects (ACh as neurotransmitter)
L vagus nerve mostly affects AV node
R vagus nerve mostly affects SA node
Decrease blood pressure and subsequently cardiac output at AV and SA node
Heart: decreases contraction, decreased SV, decreased BP
Blood vessels: vasodilation in salivary glands, GI organs, erectile tissue
Does not innervate skeletal muscle or skin. Effects there are under local control (ie metabolism), and due to
activation/inactivation of SNS.
Cardiopulmonary receptors
Baroreceptors which are sensitive to low pressure, act in opposition to baroreceptors in aortic arch and carotid sinus.
Nerve terminals located in the pulmonary arteries, vena cavas, atria, and ventricles and muscles
Two types of atrial receptors: A and B

A receptors sense atrial contraction and depolarize

B receptors sense atrial volume and depolarize when the atria are filling
Ex: increase blood volume in atria
Short term response depends on the previous heart rate. If it was low before, it will increase; if it was high
before it will decrease due to baroreceptors firing.
Long term (maintain increased blood volume). Vasodilation in the kidney stimulates atrialnaturetic
hormone release, and inhibits antidiuretic hormone release. This increases Na secretion, which increases
H2O secretion, increases urine volume, and therefore lowers blood volume.
Humoral receptors- this is control at the hormonal level, and is referring to the rennin/angiotensis system. See page 7 of Dr. Garcias
Decreased blood volume is sensed by the kidney
Juxtaglomerular cells release rennin.
Renin functions to transform angiotensinogen to angiotensin I. Angiotensin I is converted to the active form angiotensin II in
the lungs and kidneys by ACE.
Angiotensin II functions to:
o Release aldosterone from the adrenal gland which increases Na (and therefore water) reabsorption in the kidneys.
o Affect Na/H transporter of kidney to retain sodium
o Increase total peripheral resistance by affecting small vessels smooth muscle
o Cause release of ADH
o INCREASE BLOOD VOLUME, PRESSURE, AND SODIUM, brings system back to normal
Intrinsic/local control- three things which can all act to modify TPR at the arteriole level.
1. Autoregulation by myogenic (heart contraction) effects, metabolic products, and endothelial products.
a. Autoregulation refers to the ability to maintain a constant flow when the pressure chages.
i. Increased pressure initially causes an increased flow, but smooth muscle relaxes and flow is returned back
to normal
ii. Decreased pressure initially causes a decreased flow, but smooth muscle contracts and flow is returned
back to normal
iii. These have effects on resistance! (know the effects)
b. Myogenic- explained by stretch receptors in plasma membranes of smooth muscle cells. Increased or decreased
pressure causes the blood vessels to strech or relax, which is recognized by the stretch receptors. These will cause
constriction or relaxation of muscle to maintain constant flow.
2. Active hyperemia (dilation of arteriolar smooth muscle) stimulated by metabolic and endothelial products during exercise
a. With moderate exercise cardiac output increases from 5L/min to approx. 12L/min
b. Blood vessels are arranged in parallel, so the body can divert blood flow to or away from different areas. Different
tissues can receive the same or different proportions of the total cardiac output depending on the activity. For
example during exercise skeletal muscle will receive a greater percentage of cardiac output. Blood flow to the brain
is always constant. Therefore when cardiac output is increased, the percentage of total cardiac output which goes to
the brain will be decreased. (see p. 10 of this lecture)
3. Reactive hyperemia (increase of blood flow to an organ) by buildup of metabolic and endothelial products or waste, usually
due to an oxygen debt.
a. Increased blood flow to a tissue in response to an oxygen debt
b. Important in heart following a transient ischemic episode (ischemia-lack of proper blood flow/oxygen supply)

Metabolites released following an ischemic episode

Lactate, adenosine, or potassium released from heart or skeletal muscle in an attempt to restore normal flow.
Shear stress on endothelial cells caused by blood flow causes NO to be released, this acts on smooth muscle and causes
Other endothelial vasodilators: Prostaglandins, prostacyclin, PGE2
Endothelial vasoconstrictors: Thromboxanes, endothelin
CV7 - Microcirculation
Capillaries branch from arterioles
Unlike the smooth muscle cell lining in arterioles, capillaries have endothelium that is important for the filtration of blood and the
absorption of nutrients
Met arterioles branch from the arterioles
Some capillaries will still branch off of the arterioles but some will branch off of the met arteriole (see picture in lecture slide)
Precapillary sphincter- increased amount of smooth muscle where the arteriole becomes capillaries
This system regulates the nutritional flow to the organs

If nutrients are not needed, the sphincter will close, blood will go through the met arteriole and directly to the vein (it bypasses the
capillaries) this way you are conserving nutrients/ gases for the areas in which they are needed
In contrast, active tissues which are in need of nutrients/ gases, the precapillary sphincter will relax so blood will flow through it to the
This system also regulates how much blood goes where
If youre older, there is less elasticity in the arterioles, they cannot vasodilate as much, which leads to decreased blood flow which
leads to an oxygen debt which can lead to pain
The capillaries still need pressure in order to move the blood forward
How can they withstand this pressure with just thin layer of endothelium?
Law of Laplace!
Tension = pressure times radius (P X r)
Bigger radius = bigger tension
Tension is how much force needs to be applied to make the wall split
(capillaries are small and so there is little tension as opposed to the aorta for example)
Ex) aneurysm diameter increases therefore tension increases, more prone to break
Pinocytosis, diffusion and filtration are the three methods used for exchange of nutrients
Field pores- aqueous holes in the endolthelial wall that allow exchange
Plasma proteins are usually relatively large and stay in the blood
Pinocytosis- is the movement of larger proteins through the use of vesicles out of the capillaries
Ions/glucose/ amino acids- pass through the water pores- diffusion based on concentration gradient
O2, CO2 (lipid soluble) can cross the endothelial wall
Flow limited diffusion- the more flow you have in one tissue, the more flow of blood
The more open capillaries= greater blood flow
He then drew a graph explaining how on the arteriolar side of the capillaries there is a high concentration of molecules
You will see a decrease in the concentration of small molecules in the capillaries as you go from arteriolar to venous side because most
of them are small enough to go into the tissues whereas the concentration of medium to large sized molecules will not decrease as
much as more of them will stay in the capillary
Also, notice that some cells are farther from the capillary than usual and this leads to edema because the molecules do not reach the
tissue cells and this leads to a build up of fluid in the interstitia
Endothelial lining has fenestrations where the endothelium is discontinuous
Fenestrations are bigger in kidney/intestine/liver, form= function!!
These organs are involved in filtration and absorption and thus need many fenestrations
In contrast, the brain has the blood brain barrier and thus has fewer fenestrations and a more continuous endothelium
Forces on capillaries
When resistance on the arteriolar side is reduced, pressure in the capillaries is increased and when vasodilation on the venous side
occurs pressure in the capillary is also increased, this leads to a pressure gradient in the capillaries which favors filtration
(so high pressure in the capillaries favors filtration)
Oncotic pressure- proteins in the capillaries exert oncotic pressure which moves water down its gradient into the capillaries
Filtration- bring fluid out of the capillaries
Absorption- bring water into the capillaries
Ex) kidneys you have mostly filtration and in liver you have mostly absorption
Albumin is important for maintaining protein concentrations in capillaries which is key for maintaining oncotic pressure, without
albumin, there is less movement of water into the capillaries and more risk for edema
Also, pressure increases on either arteriolar or venous side increases pressure in capillaries and this will increase filtration
Most of the fluid filtrated out is reabsorbed by the capillary

Whatever is not reabsorbed will move into lymphatic vessels and go back to the heart for recirculation
Lymphatic vessels have a thin cell lining, cells are not as tightly attached as in the endothelia, this makes lymphatic vessels more
permeable, when excess fluid exists it goes into the lymphatic vessels and then becomes lymph
Lymphatic vessels- unidirectional flow back to the heart because of the presence of valves
In cases of burns, permeability of the capillaries increase, fluid builds up in the interstitial space, lymphatic vessels are not working
properly and so they dont take up all the fluid properly
Decrease in the blood volume leads to a decrease in blood pressure
Less blood goes back to the heart which leads to decreased stroke volume and decreased cardiac output
The body responds by increasing heart rate/ BP
Two factors affecting venous return
Respiratory pump- in horizontal position, body is at atmospheric pressure but pressure in thorax is below that so you have a pressure
gradient in your body
Cardiac pump- opening of the ventricles functions as a suction cup and sucks in more blood from the atria and the veins therefore
increasing venous return
When you stand up, your blood pools at your feet and thus there is less blood going to your heart, your blood pressure will drop and so
your body responds by increasing the heart rate and BP
This sympathetic stimulation increases the pressure in the capillaries as well which we know will increase filtration which is what
leads to the swelling of ankles/ feet
CV #8- Special Circulations
Coronary circulation
The force that is actually used to propel blood compresses the coronary vasculature on the heart
itself, consequently:
Epicardial pressure (outside the cardiac muscle) < endocardial pressure (innermost layer)
When the heart is in systole (compression of heart muscle) endocardial blood flow drops to nearly zero
Flow increases during diastole as a result of local metabolite release (stimulated by O2 debt)
Myocardial oxygen balance flow chart (determinants of coronary perfusion)

Thus as metabolic demand increases coronary resistance decreases coronary perfusion increases
*Clinical tachycardia (rapid heart rate) decreases diastolic time period thus decreasing time for
coronary perfusion increased metabolic demand
Reaction Hyperemia
Basically clamping the coronary artery and upon release you get a corresponding increase in
perfusion to compensate for the blood flow lost during clamping
Local factors such as NO, Adenosine, and ATP sensitive K+ channels mitigate the response via
prolonging K+ effusion shorter plateau of AP
As always, diffusion of O2 is flow limited (depends on number of capillaries and open/closed state)
Clinical: transient ischemia can be temporarily compensated for in the body via collateral circulation
Skin Circulation
Has arterio-venous (A-V) shunts (aka metarterioles)
Properties of A-V shunts
Thick muscular walls
Under sympathetic not metabolic control

Responds to reflex activation by temperature receptors

No reactive hyperemia
Means of conserving heat through metarteriole bypass route
Arterioles though, are under local control e.g. autoregulation and reactive hyperemia
Temperature control in skin (acts on the hypothalamus)
Cold: 0-15 degrees = vasoconstriction of arterioles and AV shunts
Below 0 = vasodilation
Warmth: vasodilation
Skeletal Muscle Circulation
Sympathetic innervations = vasoconstriction
Due to large vascular bed it is important for regulating blood pressure
Under neural and local factor control

Notice that skeletal muscle exhibits both active intrinsic vasodilation and extrinsic vasoconstriction while
skin vessels exhibit only vasoconstriction (NO ACTIVE VASODILATION IN SKIN)
Cerebral Circulation
Regional blood flow is associated with regional neural activity
Little or no sympathetic influence
PaCO2 vasodilation across BBB
Acidic pH in CSF vasodilation
K+ seizure or hypoxia
Adenosine increased levels during seizure/hypoxia
Autoregulated between 60-160 mm Hg (but at this high pressure BBB is compromised)
Blood vessels in the brain exhibit reactive hyperemia
Gastrointestinal Circulation
25% of Cardiac Output to liver and 10% to SI
Sympathetic vasoconstriction
Local: metabolic
Adenosine: increases during arterial occlusion (enhances food absorption)
Gastrin/cholecystokinin increase blood flow during digestion
During congestive heart failure fluid accumulates in the right heart fluid from liver enter the abdominal
Fetal Circulation

Lungs inactive (high R)

O2 tension low but Hb has higher O2 affinity due to the lack of 2,3 BPG
Fetal shunt:
RV Pulmonary artery via ductus arteriosis aorta
Blood gets to the fetus via the umbilical vein
Blood from RA LA via foramen ovale (R/L atrium work in parallel)
Summary of fetal blood circulation changes at birth:

CV9-Cardiac Dynamics and Regulation of Cardiac Output

2 Phases of Cardiac Cycle:
1.) Systole
Isovolumetric Ventricular Contraction
Ventricular Ejection
2.) Diastole
Isovolumetric Ventricular Relaxation
Ventricular Filling
Atrial Contraction
Pressure Profiles in the Blood Vessels
As blood flows through the systemic circulation, pressure decreases progressively because of
resistance to blood flow.
Pressure HIGHESTAorta and Large Arteries
Pressure LOWEST Venae Cavae
Largest decrease in pressure occurs across the arterioles because they are the site of
highest resistance.
Mean Pressures in the systemic circulation:
o Aorta: 100 mmHg
o Arterioles: 50 mmHg
o Capillaires: 20 mmHg
o Vena Cava: 4 mmHg
Pressure Profiles in the Heart

Law of Laplace
Assumes shape of heart as a sphere to make conclusions about affect of geometry and tension on
P = 2HT
P: Pressure
H: Thickness (height)
T: Tension
r: radius
In words, the Law of Laplace for a sphere states that the greater the thickness of the wall of the
sphere (ie: the left ventricle), the greater the pressure that can be developed.
This is important in explaining why the left ventricular wall is thicker than the right ventricular wall
because the left ventricular wall must develop a greater pressure to eject blood.
It is also important in seeing the compensatory affect
Ventricular wall thickness will increase if the ventricle has to pimp against increased aortic pressure
(ie: hypertension).
Therefore, in systemic hypertension, the left ventricle will hypertrophy.
In pulmonary hypertension, the right ventricle hypertrophies.
Stroke Volume, Cardiac Output, and Ejection Fraction
1. Stroke Volume (SV)
Is the volume ejected from the ventricle on each beat.
Expressed by:
SV: Stroke Volume
EDV: End Diastolic Volume
ESV: End Systolic Volume
2. Cardiac Output (CO)
Expressed by:
CO = SV x HR
CO: Cardiac Output
SV: Stroke Volume
HR: Heart Rate
3. Ejection Fraction (EF)

Is the fraction of end diastolic volume ejected in each stroke volume.

Is related to contractility.
Is normally 0.55, or 55%.
Expressed by:
EF: Ejection Fraction
SV: Stroke Volume
EDV: End Diastolic Volume
4. Venous Return (VR)
Is equal to Cardiac Output!!
Expressed by:
VR = HR x LV
VR: Venous Return
HR: Heart Rate
LV: Loading Volume
Changes in Cardiac Output with Exercise

Heart Rate, HR
Stroke Volume, SV
Cardiac Output, CO
Arterial Pressure
Pulse Pressure
Total Peripheral Resistance, TPR
Arteriovenous 02 difference


(due to increased stroke volume)
(due to vasodilation of skeletal muscle beds)
(due to increased O2 consumption)

Frank-Starling Relationship
Describes the increase in SV and CO that occur in response to an increase in VR or EDV.
Is based on the length-tension relationship in the ventricle:
o EDV cause Ventricular fiber length, which produce Tension developed.
Is the mechanism that matches CO to VR; the greater the VR, the greater the CO.
Changes in contractility shift the Frank-Starling curve up (ed Contractility) or down (ed

Increases in contractility cause in increase in cardiac output for any level of right atrial
pressure or EDV.
Decreases in contractility cause a decrease in cardiac output for any level of right atrial
pressure or EDV.
Is the intrinsic ability of cardiac muscle to develop force at a given muscle length.
Is also called inotropism.
Is related to intracellular [Ca2+].
Can be estimated by ejection fraction.
Positive inotropic agents produce increase in contractility.
Negative inotropic agents produce decrease in contractility.
What Causes Increase in Contractility? (aka What are Positive Inotropic Agents?)
1. Increased HR
When more action potentials occur/unit time, more Ca2+ enters the myocardial cells
during the AP plateaus, more Ca2+ is released from the SR, and greater tension is
produced during contraction.
Examples of Increased HR:
o Positive Staircase (Bowditch staircase): Increased HR increases the force of
contraction in a stepwise fashion as the intracellular [Ca2+] increases
cumulatively over several beats.
o Postextrasystolic Potentiation: The beat that occurs after an extrasystolic beat has
increased force contraction because extra Ca2+ entered the cells during the

2. Sympathetic Stimulation
Sympathetic Stimulation is by catecholamines acting on 1 Receptors
Increases Contractility by Increasing the inward Ca2+ current during the plateau of
each cardiac AP.
Catecholamines (ie: Norepinephrine) act on GPCRs. This Activates Adenyl Cyclase, which
increases cAMP levels, which activate kinases (ie: PKA) to P-late enzymes (such as
Sympathetic Simulation also increases the activity of the Ca2+ pump of the SR; this
occurs by P-lation of Phospholamban.
As a result, more Ca2+ is accumulated by the SR, therefore more Ca2+ is available
for release in subsequent beats.
3. Cardiac Glycosides (digitalis)
Increase force of contraction by inhibiting the Na+/K+ ATPase in the myocardial cell
As a result of this inhibition, intracellular [Na+] increases, diminishing Na+ gradient
across the cell membrane.
Na+-Ca2+ exchange (a mechanism that takes Ca2+ OUT of cell) depends on the size of
the Na+ gradient.
So, no Na+ gradients means no Ca2+ leaves the cell!

Increase in intracellular [Ca2+] good for contractility!

What Causes Decrease in Contractility? (aka What are Negative Inotropic Agents?)
1. Parasympathetic Stimulation
Parasympathetic Stimulation is by ACh acting on Muscarinic Receptors.
Decreases Contractility by Decreasing the inward Ca2+ current during the plateau of
each cardiac AP.
2. Decreases in pH (Acidosis), decreases force development and contractility.
NOTE: Vagal Effects predominate! There is quick on/off response of vagal effects and sympathetic affects
in absence of vagal are strong.
Indices of Contractility
1.) Peak Rate of Pressure Rise (dP/dt)
2.) Peak Aortic Flow Velocity (dV/dt)
3.) Ventricular Ejection Fraction (SV/EDV)
Excitation-Contraction Coupling: Cardiac vs. Skeletal
NOTE: this is from previous exam, for more detailed explanation see notes from EXAM1
Basically, in Cardiac CICR predominates and in Skeletal VICR predominates.

CV Lecture 10: II. Cardiac Dynamics and Regulation of Cardiac Output

1) Describe the Frank/Starling Law of the Heart and illustrate this graphically.
2) How are the length tension relationship and calcium sensitivity involved in the Frank/Starling Law of the Heart?
3) Define pre-load and afterload.
4) Show graphically how preload, afterload, and contractility affect variables such as ESV, EDV, ESP, and SV.

5) How do changes in myocardial contractility and blood volume produce a compensation in heart failure?

In the heart, inc [Ca] is graded while in skel it is all or none.

In the heart, there is no summation, but instead a modulation of response to [Ca] by phosphorylation of 1) phospholamban (to
store more Ca in SR), 2) Ca pump (SERCA and on cell membrane) and 3) TnI (increases Ca sensitivity inc crossbridge
(+) ionotropic inc. contractility
(-) ionotropic dec. contractility
o SLIDE 4: Memorize positive and negative ionotropic agents. I dont think we need to know the source.
Frank-Starling law of the heart (aka cardiac length tension relationship):
o Describes the increases in SV and CO that occur in response to increased venous return or EDV.
As you increase the length, you increase the force development (plateaus at a long lengths). At longer
lengths, the heart contracts more forcibly producing more tension.
Increases in EDV cause an increase in ventricular fiber length, which produces an increase in developed
o It ensures that CO = venous return
o Increased contractility cause an increase in CO or EDV
o Decreased contractility cause a decrease in CO or EDV.
o Cardiac muscle length range 1.8-2.4um.
o As you increase the length, you increase myofibril sensitivity to Ca and you get more bang for your buck for the
same amount of Ca. As you stretch the sarcomere, TnC will much more easily bind Ca inc force and cycling
Preload VOLUME of ventricular filling
Afterload PRESSURE exerted by blood leaving the heart
o Valve will not open until the pressure in vent increases past the afterload pressure
a. pre-load/EDV
a. Mitral valve closes
b. Afterload/ESV
a. Aortic valve opens
c. Aortic valve closes
d. Mitral valve opens
a-b isovolumetric contraction
b-c ventricular ejection
c-d isovolumetric relaxation
d-a ventricular filling

Inc preload inc vent filling, inc EDV, and inc end-diastolic P. but
NO CHANGE in afterload more forceful contraction inc
ejection P inc ejection fraction inc SV
Inc afterload = inc aortic P must develop greater P in vent to
overcome it inc ejection P, inc ESV, inc end-systolic P, dec

B/c aortic P is higher, valve will close sooner inc ESV and ESP dec SV
In the 2nd beat, the system will compensate towards a more normal SV at the expense of a higher EDV leading to inc
tension (T) on vent walls eventually causing vent hypertrophy and eventual dilated cardiomyopathy in the long term
(heart failure)
o Increasing symp stimulation of the heart leads to inc contractility inc vent P at any given EDV. There is a
decrease in vent P at any EDV with heart failure and the system compensates by increasing symp stim to return vent
pressure closer to normal.
Increased contractility inc endsystolic P inc SV dec ESV.
o On the 2nd beat, same endsystolic P as beat one dec EDV dec ESV returns SV to normal.
SLIDE 24: understand how diseases affect pressure volume loops.
With exercise, you get (inc venous return inc EDV) and also (inc contractility dec ESV). Both work together to
increase SV.

CV 11: III. Regulation of Cardiac Output and Cardiac Work

1. How do changes in Venous return affect cardiac output? What physiological mechanisms control venous return?
Venous return (VR) is the flow of blood back to the heart. Under steady-state conditions, venous return must equal cardiac output
(CO) when averaged over time because the cardiovascular system is essentially a closed loop. Therefore in any conditions which
may increase Venous Return (by increasing Central Venous Pressure) will cause an increase in Cardiac Output.
Factors Affecting Venous Return:
Muscle pump: A major mechanism promoting venous return during normal activity (e.g., walking, running) is the muscle pump
system. Peripheral veins, particularly in the legs and arms, have one-way valves that direct flow away from the limb and toward the
heart. Veins located within large muscle groups undergo compression as the muscles surrounding them contract, and they become
decompressed as the muscles relax. Therefore, with normal cycles of contraction and relaxation, the veins are alternately compressed
and decompressed (i.e., "pumped"). Muscle contraction propels blood forward through the open venous valves and impedes back flow
in the muscle with closed venous valves. During muscle relaxation, the valves open and blood flows into and fills the venous segment,
but only from the arterial side. The net effect is that the cycle of compression and relaxation propels the blood in the direction of
the heart. Venous valves prevent the blood from flowing backwards, thereby permitting unidirectional flow thereby enhancing
venous return. When a person is standing, postural muscles in the legs alternately contract and relax to keep the body in balance. This
muscle activity promotes venous return and helps to maintain cardiac output.
Respiratory pump: During inspiration, the chest wall expands and the diaphragm descends. This causes a negative pressure in the
thorax (suction effect), which leads to expansion of the lungs and cardiac chambers. This expansion causes the intravascular and
intracardiac pressures (e.g., right atrial pressure) to fall. As right atrial pressure falls during inspiration, the pressure gradient for
venous return to the right ventricle increases, thus more blood returns to the heart. During expiration, the opposite occurs and the
venous return is decreased. Inspiration causes an increase in venous return
Gravity: Gravitational forces significantly affect venous return and therefore cardiac output, and arterial and venous pressures. This is
shown by the example of a person who is lying down and then suddenly stands up. As the person stands, gravity acts on the vascular
volume so that blood accumulates in the lower extremities. Therefore, venous volume and pressure becomes very high in the feet and
lower limbs when standing. This shift in blood volume decreases thoracic venous blood volume and therefore decreases central venous
pressure. This change causes a decrease in right ventricular filling pressure (preload), leading to a decline in stroke volume by the
Frank-Starling mechanism. When a person initially stands, cardiac output and arterial pressure decrease; The flow through the
entire systemic circulation falls because arterial pressure falls more than right atrial pressure, therefore the pressure gradient
driving flow throughout the entire circulatory system is decreased.
The effects of gravity are compensated by sympathetic vasoconstriction of the veins and the use of the skeletal muscle pumps
(specifically the valves).
Sympathetic Vasoconstriction: In blood vessels, sympathetic activation constricts arteries and arterioles (resistance vessels), which
increases resistance and decreases distal blood flow. Sympathetic-induced constriction of veins (capacitance vessels) decreases venous
compliance and blood volume, and thereby increases venous pressure. The overall effect of sympathetic activation is to increase
cardiac output, by increasing venous pressure.
Dr. Kenndy also makes mention of the hearts contractility and suction effect (as contraction increases, the suctions effect increases) as
other factors that will increase central venous pressure and therefore cardiac output.
2. Show how the cardiac function curve is generated graphically and understand how changes in preload, contractility, and
afterload alter the curve.

Contractility: Contractility is the intrinsic ability of cardiac muscle to develop force for a given muscle length.
An increase in Contractility = an elevated stroke volume at each End Diastolic Volume; and less End Diastolic Volume is required to
generate a given Stroke Volume (Top line of the graph)
Preload: Preload is the muscle length prior to contractility, and it is dependent on ventricular filling (or end diastolic volume.) This
value is related to right atrial pressure. The most important determining factor for preload is venous return.
An increase in Preload causes an increase in End Diastolic Volume and an increase in cardiac output. (he does not have a picture for
this in lecture)
Afterload: Afterload is the tension (or the arterial pressure) against which the ventricle must contract. If arterial pressure increases,
afterload also increases. Afterload for the left ventricle is determined by aortic pressure, afterload for the right ventricle is determined
by pulmonary artery pressure.
An increase in Afterload causes a reduced stroke volume at each End Diastolic Volume; and an elevated End Diastolic Volume to
achieve the same Stroke volume (bottom line of the graph.)
3. Calculate the Cardiac Output using the Fick Principle and determine the Cardiac Index
Fick Principle can be used to compute cardiac output (CO) indirectly from whole body oxygen consumption (VO 2) and the mixed
venous (O2ven) and arterial oxygen contents (O2art).
The principle states that the oxygen quantity delivered to the lungs in the pulmonary arteries plus the oxygen quantity added by the
lungs must equal the amount carried away from the lungs in the pulmonary veins.
CO =

(O2vein O2artery)

Cardiac Index = Cardiac Output (calculated from above)

M2 body surface area (typically 1.6 m2)
Normal range of cardiac index is 2.6 - 4.2 L/min per square meter.
If the CI falls below 1.8 L/min, the patient may be in cardiogenic shock.
4. How is Cardiac Minute calculated? What is meant by pressure work and volume work and which has a higher cost?
Cardiac Minute work is the rate of work in the cardiac muscle.
Cardiac Minute Work = Aortic Pressure X Cardiac Output
Pressure Work Volume Work
Development of Pressure
Work of Ejecting Blood

Pressure work is more expensive than volume work. This is measure by the oxygen consumption required by the heart to do each.
The energy requiremens for pressure work are higher than those of volume work. More O2 is consumed to develop pressure gradient
in the heart than is used to eject the blood in cardiac output
5. Use the Law of LaPlace to describe why a dilated heart has greater energy costs
A dilated heart is caused by Cardio Myopathy which causes the thinning of the ventricular walls and therefore a lager radius.
An increase in Radius and End Diastolic volume Increases Tension creating a higher demand for ATP therefore
demanding more O2
Meanwhile, a healthy heart has a comparatively smllaer radius and End Diastolic Volume which Lowers the tension, requires less ATP
and therefore less O2
Circulation and Cardiac Output: CV12
Venous P affect R. Ventricle filling affects CO (cardiac output)
If inc. VP (diff btn VC and peripheral venous pressure) from inc. R. Ventricle filling, inc. end diastolic volume inc. CO
Venous compliance has (-) affect on VP, b/c relaxation of smooth muscle inc. stretchability, which dec. VP
If inc. Venous return (inc. blood flow to central vein), then will inc. VP
o Venous SM contractility
o Inc. total BV (blood volume)
o Resp. movements will inc VP by dec. interthoracic pressure
o Skeletal muscle pump- compresses veins inc. blood flow b/c one way valves
o Gravity- from lying to standing, venous pooling less venous return
o Ventricular compliance (low) can inc. VP
o Atrial contractility inc. VP
HR when above 170 compromises time for vent. Filling, so (-) affect on VP
*Inc. CO dec. BV for next, so has (-) affect on VP
o if dec. CO, that inc. central VP or r. atrial pressure
o where CO = 0, that is the (Pmc) mean circulatory pressure (7mm Hg for normal)
where heart is stopped, all the pressures can equilibrate (identical). Pressures in veins = arteries, etc.
o Only two types of volumes in veins:
1) Unstressed- very little pressure being developed
2)Stressed- after 4L, each addition lead to rapid inc. in of pressure in veins
Observe changes in BV as it relates to central VP(venous pressure) see p.6
o If inc. BV curve shifts rightwhich inc. VPalso inc. Pmc (10.5)
o If dec. BV curve shifts leftdec. VPalso dec. Pmc (5.2)
Pmc changes with changes in BV
o BV dec. (e.g. hemorrhage)- no change in unstressed volume, but dec. in stressed volume, dec. Pmc
o BV inc. (transfusion)- no change in unstressed volume, but inc. in stressed volume, inc. Pmc
o Venoconstriction dec. unstressed volume, inc. Pmc
o venodilation(syncope/blood pooling) inc unstressed volume, dec. Pmc
this is the same with change from going to reclining to standing position quickly-venous poolingdec.
Sympathetic stimulation and Vascular Fxn
o If inc. TPR (art. constriction) shift left, dec. CVP, no change Pmc
o If dec. TPR (art. dilation) shift right, inc. CVP, no change Pmc
Cardiac fxn curve- (looks at VP affect on CVP)
o Inc. CVP inc. CO
Vascular fxn curve (looks at CO affect on CVP)
o Inc. CO dec. CVP, see slide 13!
Interaction of both curves Cardiovascular Operating point- where at equilibrium. Tries to reestablish equilibrium.
o Symp. Stimulationinc contractinc COdec. CVP
o Hemorrhage dec. BVdec COdec CVP
Response to hemorrhage:
1)inc. symp. Stimulationinc HR, contractility, CO
2)venosonstrictinc. Pmc, inc. CVP

3)vasoconstrictinc TPRinc CO
Inc. in MAP (mean art. pressure) dec. CO (because aortic valve cant open)
o Inc. in TPR (hypertension)inc. MAP (or afterload)dec. CO, no change Pmc
Will always get a dec. CO, but CVP can dec/inc.
Heart Failuredec. contractilitycurve to rightdec. CO
o Response: inc. BVby retention of fluid (hypervolemia)inc. CVP, Pmc. The compromise to get back to normal
CO is the inc. in CVP!!!
o Severe is more dec. in CO, and more inc. in CVP. CO is not normal, so there is more pressure to inc. BV
furtherleads to peripheral edema
On flip side, if can inc. symp. stimulation of veinsinc CO = Cardiac Reserve
o Happens in exercise inc. symp, and inc. HR