HEART

The work of the heart in one

-70ml/beat, 7200 l/day
life is equivalent to lifting 30
-35 million beats /year, 2.5 billion beats/life
tons to the Mount Everest

Myocardial O2 Demand
The cardiac muscle always depends on aerobic oxidation of substrates even
during heavy exercise
Therefore, The cardiac muscle has the highest O2 uptake (VO2) compared
to other tissues of the .

This is achieved by a dense network of capillaries, all is perfused at rest (no

capillary reserve)
& by maximal extraction of O2 from RBCs (almost no O2 extraction reserve)
 What determines Myocardial O2 Demand?
The direct factor is Left Ventricular Work (ventricular contraction to eject
blood)

VO2 is increased by an in;

1.Afterload. 2.Contractility. 3.Heart rate. 4.Preload

How this affects Coronary blood flow?

The fact that there is no O2 reserve for cardiac muscle makes the
increase in blood flow is the alternative for an extra need for O2

Thus, any restriction in flow increased risk of tissue damage

The increased flow is due to functional hyperaemia which explains the
major role of local metabolic factors in regulating coronary circulation
 Physiological Anatomy of Coronary Circulation

Coronary Venous drainage:

Coronary sinus draining

~90% of Lt ventricle
into Rh atrium
 Coronary artery dominance
The artery that supplies the posterior descending artery (PDA) determines the
coronary dominance.
If PDA is supplied by the right coronary artery (RCA), then the coronary
circulation can be classified as "right-dominant". (70%)
If PDA is supplied by the circumflex artery (CX), a branch of the left artery, then
the coronary circulation can be classified as "left-dominant". (10%)
If PDA is supplied by both the right coronary artery (RCA) and the circumflex
artery, then the coronary circulation can be classified as "co-dominant". (20%)
Coronary Artery
Anatomic Region of
(most likely
Heart
associated)
Inferior Right coronary
Left anterior
Anteroseptal
descending
Left anterior
Anteroapical
descending (distal)
Anterolateral Circumflex
Right coronary
Posterior
artery
Regional myocardial blood flow can now be measured noninvasively in by MRI, CT,
and PET.
 Coronary Blood Flow
Normal CBF = About 5 % of COP. The resting CBF in the resting human is
about 225 ml/min.
Arterial oxygen extraction is 7080%, compared with 25% for the rest of the
body. Therefore, oxygen consumption must principally be met by an
increase in CBF, which may 5 folds during exercise.
During strenuous exercise, the heart in the young adult increases its COP 4-
7 folds, and it pumps this blood against a higher than normal arterial
pressure. Consequently, the work output of the heart under severe
conditions may increase 6-9 folds. CBF increases 3-4 folds to supply the
extra nutrients needed by the heart.

This increase is not as much as the increase in workload, which means that
the ratio of energy expenditure by the heart to coronary blood flow
increases.
Thus, the "efficiency" of cardiac utilization of energy increases to make up
for the relative deficiency of coronary blood supply.
 Epicardial versus Subendocardial Coronary Blood
Flow. Phasic Changes in Coronary Blood Flow during
Systole and Diastole

There is strong compression of LV muscle around the intramuscular vessels during

systolic contraction.
During diastole, the cardiac muscle relaxes and no longer obstructs blood flow through
the left ventricular muscle capillaries, so blood flows rapidly during all of diastole.
 Coronary Bl. Flow is Phasic
Total Coronary flow is greater during diastole
Therefore, The most crucial factors for perfusing coronary arteries are:
1. aortic pressure. 2. duration of diastole.
An in HR, with diseased CA, will diastolic period & CBF anginal pain
The lowest coronary flow occurs during isometric contraction phase.
The greatest flow occurs during isometric relaxation phase .
Perfusion of arteries supplying Rh ventricle is less affected by contracting
myocardium because tension developed in RV is always lower than that in LV.
The myocardial cells contain large amounts of myoglobin; a pigment that
can carry O2 acting as O2 store

It is saturated with O2 at very low O2 tension

Releases its O2 during systole when blood flow is reduced thus ensuring
continuous supply of O2 to myocardium
 Regulation of Coronary Circulation
Intrinsic; (Local Regulatory). Extrinsic; Neuro-Humoral Control
I- Intrinsic Regulation (Metabolic)
The marked increase in coronary blood flow following an occlusion of
coronary flow led to the concept that:
A metabolic link exists between myocardial O2 demand and the level of
coronary blood flow
Thus, O2 demand Bl.Flow O2 demand flow
This Metabolic link may be:
Hypoxia itself has a direct relaxant effect
Or hypoxia leads to release of:
1. Adenosine; a degradation product of AMP,
accumulated. 2. Lactate & H+. 3. PG I2
All come to stimulate Nitric oxide release
from endothelium leading to vasodilatation
CBF
 II- Extrinsic Regulation
A] Nervous
1- Sympathetic stimulation
Direct Effect:
1-adrenorecptor mediated VC. 2-adrenoreceptor-mediated mild VD
Indirect:
1mediated HR metabolic activity accumulation of vasodilator
metabolites VD The Net Effect : Vaso-Dilation Coronary Bl. Flow
2- Parasympathetic stimulation
Direct cholinergic mediated moderate VD Coronary Bl. Flow
Indirect HR metabolic activity O2 demand coronary Bl.Flow
The net result is VC coronary Bl.Flow
3- Anreps Reflex
VR atrial stretch vagal stimulation coronary VD CBF
Important during muscle exercise
4- Gastro-coronary Reflex:
Heavy meals gastric distension reflex coronary VC CBF
Anginal Pain may be related to eating heavy meal
 B] Hormonal

Norepinephrine, Epinephrine, thyroxin coronary dilation

Angiotensin & vasopression coronary constriction.

 Determinants of coronary blood flow:

Coronary Perfusion Vessel wall

perfusion pressure: time: diameter

Vasomotor tone
Any increase determines the
The coronary in heart rate vessel wall
perfusion pressure: = impinges on diameter. The
interplay of
aortic diastolic diastolic time
various
pressure - left more than mechanisms that
ventricular end- systolic time regulate the
diastolic pressure and reduces coronary
(LVEDP). the perfusion vasomotor tone
time. usually favours
vasodilatation.
 Factors influencing the vasomotor tone:
4] Humoral control:
2] Autoregulation:
Most vasoactive hormones
Under resting 3] Nervous control: require an intact vascular 5] Vascular
conditions: CBF generally weak. endothelium. endothelium:
remains constant Epicardial vessels ( The peptide hormones modulates
1] Myocardial
metabolism:
between mean receptors) include (ADH, ANP,VIP, and contractility of
arterial pressures smooth muscle
stimulation calcitonin gene-related
through secretion
of 60140 mm Hg. vasoconstriction. peptide).
Hypoxia of vasoactive
Beyond this range, ADH (in physiological
causes Intramuscular and substances in
flow becomes concentration) has little response to blood
coronary subendocardial vessels
pressure- effect on CBF but causes flow, circulating
vasodilatation (2 receptors)
dependent. vasoconstriction in hormones and
directly . stimulation
stressed patients. chemical
OR vasodilatation. substances.
Probable The other peptides
releases Sympathetic stimulation Vasorelaxants are
mechanisms include: endothelium-mediated
adenosine . 1] myogenic response [predominance of EDRF,NO,
receptor activation] vasodilatation.
OR to intraluminal prostacyclin,
metabolic demand Angiotensin II bradykinin.
opens ATP- pressure changes
(fast) and 2] metabolic
myocardial blood flow. coronary Vasoconstrictors
sensitive
regulation (slow). vasoconstriction include endothelin
potassium Parasympathetic effects independent of and thromboxane
channels. are minor and weakly
The myocardial sympathetic innervation. A2.
vasodilatory.
oxygen tension and 1] It enhances calcium The net response
The vasodilatory effect of
presence of influx and releases depends on the
acetylcholine depends on
vasoconstrictors or balance between
an intact endothelium. endothelin (the strongest
vasodilators influence the two opposing
vasoconstrictor).
the range of coronary groups.
autoregulation.
2] ACE inactivates
bradykinin (vasodilator).
 Myocardial oxygen balance:
Coronary blood supply measured by diastolic pressure time index (DPTI), and =
coronary perfusion pressure X diastolic time.
Coronary perfusion pressure = aortic diastolic pressure - LVEDP.
Diastolic time =(60 s/heart rate 0.2 s).
oxygen demand measured by tension time index (TTI), and = systolic BP X systolic
time.
Systolic time = 0.2 s.
NB: systolic time is typically fixed at 200 ms, with diastole occupying the remaining
time.
The ratio DPTI/TTI = endocardial viability ratio (EVR) and represents the myocardial
oxygen supply-demand balance. The EVR is normally 1 or more.
**A ratio <0.7 is associated with subendocardial ischemia.
Example:
Such a value may be reached in a patient with the following physiological data:
Blood pressure = 180/95 mm Hg
Heart rate = 120 min1
LVEDP = 15 mm Hg.

The coronary perfusion pressure = is aortic diastolic pressure - LVEDP. = 95-15=80

DPTI = 80 mm Hg (60 s/heart rate 0.2 s) = 24 s mm Hg
TTI = 180 mm Hg 0.2 s = 36 s mm Hg
EVR = 0.67
 Diseases affecting the coronary blood flow:

1] Coronary artery disease:

Critical stenosis [diameter is 2] Hypertension: LV H.
reduced by 50%] occurs when CBF
is unable to respond to an increase The myofibrillar growth
3] Heart failure:
in metabolic demand. outstrips the capillary
network, resulting in Impaired ejection
Resting flow becomes affected if decreased capillary larger diastolic
the diameter is reduced by 80%. density. volumes, LVEDP
and coronary
With increasing stenosis, distal intramyocardial perfusion pressure.
arterioles dilate maximally to pressure
preserve flow up to the point where subendocardial blood flow.
the vascular bed is maximally
Sympathetic-
dilated. The pressure load mediated systemic
increases myocardial work vasoconstriction
Further stenosis leads to a drop in and oxygen demand. may help to
flow and flow becomes pressure improve the
dependent. Impaired vasomotor myocardial perfusion
Flow diverted into a dilated parallel response to hypoxia in but pressure load
bed proximal to a stenosis is called hypertrophied tissue that
and oxygen demand
coronary steal and can aggravate makes it susceptible to
ischemia. Flow in collaterals is also ischaemia.
often pressure dependent.
In a group of patients with systemic hypertension and left ventricular hypertrophy
(pts with valvular disaese or known CHD and diabets mellitus were excluded) the
CFR was reduced. 6 months after effective antihypertensive therapy with ACE-
inhibitor or Ca-antagonist the repeated CFR increased significantly, although it did
not reach the normal vale.
The measurements confirmed significantly reduced CFR.
 Drugs and coronary blood flow:
3] Calcium channel blockers:
Compared to the non-
1] Antiplatelet drugs,
2] Nitrates: dihydropyridines (verapamil
anticoagulants and lipid
produce nitric oxide release and diltiazem) the
lowering drugs:
vasodilatation in all vascular dihydropyridines (nifedipine):
prevent further reduction in
beds.
the vessel diameter.
more vasodilatation,
They relieve coronary
Statins inhibit HMG CoA
vasospasm but their main less inhibition of the sinus
reductase, an enzyme
benefit is to reduce preload, and atrioventricular nodes,
involved in cholesterol
afterload and to increase
synthesis.
maximal coronary dilation. and less negative inotropy.
Antiplatelet drugs prevent
platelet aggregation, often the
***Benefits may be prevented myocardial oxygen supply
initial step in the formation of
by reflex tachycardia. improves due to coronary
an occlusive thrombus.
dilatation and lower LVEDP.
Antithrombin agents act at
Regional blood flow is improved
various sites in the
due to dilatation of collaterals oxygen demand is lessened
coagulation cascade to inhibit
and a lower LVEDP. because of decreases in
thrombin formation.
contractility and pressure
load.
 Drugs and coronary blood flow:
4] Drugs acting on
angiotensin:
ACEIs conversion of A-I
to A-II.
These drugs reduce
angiotensin-mediated
vasoconstriction and enhance
myocardial perfusion by
vasodilatation ***without
reflex tachycardia.
It also regulates fibrous tissue
formation after tissue injury.
ARBsenhance
endothelial nitric oxide
release.
7] Vasopressors and
5] Potassium inotropes
channel openers 6] -Blockers: Both restore
[Nicorandil]is a Coronary vessels contain 2 coronary perfusion
novel anti-anginal receptors. pressure in
agent. hypotensive patients
Chronotropy and inotropy
depends on 1 stimulation.
Increased Any increase in aortic
potassium efflux HRprolongs the diastolic diastolic pressure
intracellular perfusion time and they may be offset by an
calcium and inhibit stress-induced rises in increase in
muscle myocardial contractility. myocardial oxygen
relaxation. demand related to
In patients on cardioselective
higher workload,
1-blockers, unopposed
It ***dilates both systemic stimulation contractility and
2
normal and afterload, improves ejection heart rate.
stenotic fraction, and exerts a
segments of the positive inotropic effect. In the failing heart,
coronary arteries. inotropes also reduce
the LVEDP.