Variations in myocardial perfusion

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Blood supply to the heart is affected by ventricular contraction and relaxation. Any myocardial stress is expected to alter underlying myocardial geometry and, in turn, geometry of intramyocardial vessels. This may affect vascular resistance and flow. Forces acting on a myocardial segment may include interactions between myofibres and adjacent vessels, intramyocardial tissue (fluid) pressure, cavity pressure transmitted as radial stress, myofibre force transmitted tangentially, and pericardial pressure. Intramyocardial tissue pressure possibly constitutes a major component of coronary vascular resistance. It differs between right and left ventricular wall, atrial and ventricular chambers, and epicardial and endocardial layers, and it varies with systole and diastole.

During systole, the myocardial fibre bands that encircle both ventricles exert lateral shearing forces on the perpendicularly penetrating intramyocardial branches of the large epicardial vessels. This may entirely abolish flow to certain regions of the myocardium.121 At the same time, however, those intramyocardial vessels running parallel to the muscle fibres are compressed during systole which propagates blood further downstream. Coronary venous blood is drained almost entirely in systole partly as a result of this squeezing effect of myocardial contraction. This in itself promotes coronary arterial inflow.122

Resting myocardial perfusion

Although mean resting myocardial blood flow in all larger mammals is consistently 0 610 ml/min per g,58 local flow distribution is remarkably heterogeneous varying between 20% and 200% of the mean value.123 Such flow heterogeneity most probably reflects local differences in aerobic metabolism.124 Thus, high flow areas do not represent a state of luxury perfusion, but rather reflect higher local O2 demands. They should be as susceptible to hypoperfusion as low flow areas.

Phasic myocardial perfusion

Intermittently high and low extravascular resistances during systole and diastole are responsible for the phasic pattern of coronary perfusion (Fig 4.6). In the left ventricle, extravascular compression during systole is so great that normally only 20-30% of left coronary artery flow occurs during systole.125 As a result of considerably lower systolic and, thus, intramyocardial pressure generated by the thin-walled right ventricle, right coronary arterial systolic flow constitutes a much greater proportion of total coronary inflow (30-50%)(Fig 4.6). Systolic myocardial compression increases with rises in heart rate, afterload, preload, and contractility. The relative contribution of each of these factors to the regulation of myocardial perfusion remains controversial.126 When coronary perfusion pressure is increased experimentally, systolic and diastolic components of epicardial flow increase, with diastolic flow dominating.127

The effects of contraction on phasic flow pattern seem to vary with the contractile state of the myocardium. During uniform global contraction, local intramyocardial forces rather than transmitted forces (that is, cavity

Coronary Flow And Aortic Pressure

Fig 4.6 Phasic blood flows of right and left coronary arteries in relation to aortic pressure. Whereas right coronary artery flow exists throughout the cardiac cycle, left coronary flow is largely confined to diastole. (Reproduced with permission from Berne RM, Levy MR Cardiovascular physiology, 5th edn. St Louis: CV Mosby, 1986:200.)

Fig 4.6 Phasic blood flows of right and left coronary arteries in relation to aortic pressure. Whereas right coronary artery flow exists throughout the cardiac cycle, left coronary flow is largely confined to diastole. (Reproduced with permission from Berne RM, Levy MR Cardiovascular physiology, 5th edn. St Louis: CV Mosby, 1986:200.)

pressure) are primarily responsible for the phasic flow variation.128 In a non-contracting region of myocardium, however, left ventricular pressure becomes a major determinant of phasic flow pattern.128

This dependence of flow characteristics on the contractile state may be explained by differences in myocardial behaviour during systole. During normal contraction, the myocardium stiffens and then becomes resistant to deformation by externally transmitted stress such as cavitary pressure. When contraction is absent, however, the respective myocardial segment fails to stiffen, and the intramyocardial vessels are now prone to deformation by externally applied forces.

Normal intramyocardial and peripheral epicardial coronary arteries exhibit almost exclusive forward flow during diastole. Reverse flow is frequently observed during systole.129 With coronary artery stenosis, systolic reverse flow increases whereas diastolic forward flow decreases.130 Reduced back pressure to systolic reverse flow as a result of decreased poststenotic distal pressure, and increased coronary arterial capacitance resulting from a pressure-dependent capacitance change131 may both serve as explanation.

Transmural myocardial perfusion

During the cardiac cycle, transmural flow distribution is non-uniform. Normally, subendocardial flow exceeds subepicardial flow by about 10%, resulting in an endo-/epicardial perfusion ratio of 11. As systolic intramyocardial compressive forces are greatest in the subendocardium, but low in the subepicardium, it was postulated that the subepicardium was perfused throughout the cardiac cycle, whereas the subendocardium received blood only during diastole. However, findings of possibly very little flow to the subepicardium even during systole argue against such a mechanism.118

During normal contraction, primarily subendocardial vessels are compressed,132 and a steep transmural gradient of intramyocardial pressure persists in an empty beating heart. When a beating heart is arrested, subendocardial flow has been shown to increase but subepicardial flow to decrease.78 Thus, contraction appears to augment subepicardial perfusion. It has been proposed that during cardiac contraction blood is squeezed out of subendocardial vessels and translocated in a retrograde fashion to superficial layers of the myocardium. In this way, the subepicardial vessels represent a low pressure and low resistance "sink" for any translocation of blood from deep to superficial layers. It is to be expected that the amount of retrograde flow will depend on the transmural pressure gradient. Consequently, absent global78 or regional contraction128 causes marked changes in phasic inflow to the myocardium and in transmural flow distribution, most probably by altering the transmural pressure gradient. When contraction is absent, left ventricular pressure becomes a powerful determinant of transmural flow distribution and, subsequently, the subendocardial/subepicardial flow ratio more than doubles, indicating favoured subendocardial perfusion.128

The left ventricular subendocardium is more susceptible to hypoperfusion than the epicardium, for two major reasons: (1) coronary vessels penetrate the ventricular wall from outside to inside, so that the inner layers are further away from the epicardial conduit arteries; and (2) systolic compressive force is greater in the subendocardium than in the epicardium.133 Whereas subendocardial arterioles narrow by about 20% during systole, subepicardial arteriolar diameter changes little during the cardiac cycle.134 It has been postulated that systole and diastole create a to-and-fro oscillation of blood flow in the coronary vessels that penetrates the myocardial wall from outside to inside.78 135 The oscillating flow only fills and empties intramyocardial arteries and arterioles, without providing nutritive flow to the subendocardial capillaries. At the end of diastole, blood flows from the aorta through the coronary vascular tree to all layers of the myocardium. At the start of systole, cardiac contraction produces retrograde flow in penetrating coronary arteries. Part of the retrograde flow originates at the subendocardial layers, and is diverted to the outer epicardial layers that are less compressed than the inner layers.78 134 At the onset of diastole, forward flow refills the intramyocardial vessels that had been compressed and emptied during the preceding systole. Only then does nutritive flow through the capillaries of the subendocardium begin. As a result of the oscillatory coronary flow pattern, the outer layer of the myocardium (the epicardium) is perfused throughout the cardiac cycle, but the inner layer (the subendocardium) is perfused only during diastole.

Tachycardia and intense adrenergic activation of the heart (as during maximal exercise) pose a particular threat to the subendocardium because: (1) the duration of diastole becomes very short, whereas systole hardly shortens; (2) (MTv>,) increases; and (3) intramyocardial blood volume increases as a result of metabolically-induced coronary vasodilation. Increased intramyocardial capacitance will contribute to a proportionally greater oscillatory flow, which encroaches on nutritive flow to the subendocardium. In other words, when intense cardiac stress results in high and CBF, in tachycardia, and in compromise of local metabolic vasodilator reserve, the mechanical effects of systolic compression and oscillating transmural flow may lead to subendocardial hypoperfusion.

Thus, opposing factors such as wall stiffness, regional contractility, and cavity pressure influence phasic inflow and transmural flow distribution. The net result on myocardial perfusion will depend on their interactions during specific conditions. With changes in baseline conditions, the relative importance of each of the factors will also change. During uniform global contraction, local tissue-vessel interactions and/or intramyocardial fluid pressure caused by active contraction appear to play a dominant role in determining myocardial perfusion. When regional contraction is abolished, left ventricular pressure assumes a more prominent role. This, however, does not imply that the effects of intramyocardial forces caused by contraction are simply removed when myocardial stiffness is low. Rather, changes in underlying conditions will result in complex changes in the spatial and temporal course of forces that act on intramyocardial vessels. Such considerations may help us to understand mechanisms governing myocardial perfusion under clinical conditions of regional myocardial dysfunction (such as myocardial ischaemia and "stunned" myocardium).

Coronary vascular resistance

Vascular tone of coronary arterioles larger than 100 p,m in diameter is regulated primarily by myogenic and local metabolic factors.136 Adenosine and dipyridamole produce their vasodilator effects mainly in vessels of this size. Up to 40% of total coronary resistance resides, however, in small arteries that are 100-400 p,m in diameter. 137 Vasomotor tone in these small coronary arteries is controlled by endothelial, humoral, and neural autonomic influences.138 Although these small vessels are not under direct metabolic control, they may, nevertheless, influence maximal coronary blood flow importantly. When vasodilation of the arterioles causes an increase in flow, the resultant increase in endothelial shear stress will augment NO production and, subsequently, cause vasodilation of the small arteries.22 136 Thus, arteriolar vasodilation leads to dilatation of the small resistance arteries by way of endothelium-dependent flow/shear-mediated NO release. In hyperlipidaemia, such endothelium-dependent, flow-mediated vasodilation of the small arteries may be impaired or abolished.139

The principal functions of the resistive vessels are: (1) to match myocardial blood flow to CMTOj) when metabolic demand varies; and (2) to maintain myocardial perfusion (proportionate to metabolic demand) when perfusion pressure varies. Under pathological conditions, dilatation of the resistance vessels compensates for the increase in resistance of the conduit arteries caused by stenoses. In experimental animals, as well as in humans, normal epicardial arteries vasodilate in response to increases in blood flow. This response is endothelium-dependent, because removal of the endothelium abolishes the flow-mediated vasodilation. Metabolic vasodilation of the coronary resistance vessels during exercise or pacing also causes flow-mediated vasodilation of the epicardial arteries.18

For a better understanding of vasomotor dysregulation which may lead to myocardial ischaemia, it is helpful to distinguish functionally between two components within the resistive coronary vasculature, which are arranged in series (Fig 4.7): (1) more proximal, ''prearteriolar" vessels in which vasomotor tone and flow are not metabolically regulated because of the epicardial position or thickness of the vessel wall; and (2) more distal, "arteriolar" vessels in which major pressure reductions occur, and in which tone and flow are metabolically regulated.140 As no anatomical differentiation is possible between the two segments, functional differentiation is expected to be vague.141

The continuous matching of flow to demand by the resistive vessels is so precise that myocardial O2 extraction remains practically constant over a wide range of metabolic demand and coronary perfusion pressure. The site of action and the mechanisms involved may differ, however, when flow is varied either in response to changes in metabolic demands at constant aortic pressure, or when flow is maintained in the presence of changes in aortic pressure at constant metabolic demand.

Reduction of coronary perfusion pressure to 40 mm Hg causes dilatation of vessels smaller than 100 ^m in diameter, but constriction of larger vessels.96 Two possible explanations exist for such a heterogeneous response: (1) large reductions in coronary perfusion pressure cause metabolically-induced dilatation of arteriolar vessels but a passive, low, distending, pressure-induced reduction in prearteriolar vessel diameter; or (2) reduced flow-mediated release of EDRF/NO causes prearteriolar constriction.

When CBF increases in response to metabolically-mediated arteriolar vasodilation, one would expect a proportionate increase in pressure drop across the prearteriolar vessels unless they respond with compensatory flow-mediated vasodilation. If this does not occur (as with endothelial dysfunction in coronary artery disease), pressure at the origin of the maximally dilated arterioles may decrease to an extent that impairs

Coronary Circulation

Fig 4.7 Schematic representation of pressure reduction from the aorta to capillaries. Three components of the coronary circulation can be identified: (1) conductive vessels with negligible pressure drop; (2) prearteriolar vessels with moderate pressure drop; and (3) arteriolar vessels with greatest pressure drop. (Reproduced with permission from Maseri A, Crea F, Cianflone D. Myocardial ischemia caused by distal coronary vasoconstriction. Am J Cardiol 1992;70: 1602-5.)

Fig 4.7 Schematic representation of pressure reduction from the aorta to capillaries. Three components of the coronary circulation can be identified: (1) conductive vessels with negligible pressure drop; (2) prearteriolar vessels with moderate pressure drop; and (3) arteriolar vessels with greatest pressure drop. (Reproduced with permission from Maseri A, Crea F, Cianflone D. Myocardial ischemia caused by distal coronary vasoconstriction. Am J Cardiol 1992;70: 1602-5.)

subendocardial perfusion.135 Thus, during metabolically-induced arteriolar vasodilation adequate perfusion pressure at the origin of the arterioles can be maintained only if there is an appropriate change in vasomotor tone at the prearteriolar level. Flow-mediated vasodilation on the basis of a tonic release of endothelial NO and/or other endothelium-derived relaxing factors may be primarily involved in the adaptation of prearteriolar vessel size to changes in flow.

Coronary blood flow varies little over a wide range of aortic pressures (see Autoregulation). This requires constant changes in coronary vasomotor tone and vascular resistance. Depending on the initiating stimulus, the adaptive mechanisms maintaining CBF may differ. An increase in aortic pressure may primarily trigger prearteriolar constriction, thus maintaining optimal pressure at the origin of the arterioles. On the other hand, when aortic pressure decreases metabolically-induced arteriolar dilatation, in addition to flow-mediated prearteriolar dilatation may be required to maintain CBF.

It is the traditional view that myocardial ischaemia in coronary artery disease is caused by a fixed or dynamic obstruction of large conduit coronary arteries resulting in a critical reduction in perfusion pressure at the origin of fully dilated arterioles. Clinical studies suggest, however, that myocardial ischaemia can also be the result of constriction of small, distal, resistive coronary vessels.142 Such small vessel constriction can result from dysfunction of either prearteriolar or arteriolar vessels. The mechanisms of the abnormal behaviour of the distal resistive vessels resulting in myocardial ischaemia can be multiple, and may involve different sites.143 144

The concept that coronary vascular resistance resides in large conduit arteries and, primarily, in small resistance vessels practically ignores the contribution of the venous system to total coronary vascular resistance. Whereas under control conditions only 7% of the total coronary vascular resistance resides in veins that are more than 150 p,m in diameter, under conditions of vasodilation with dipyridamole the total contribution of the venous component increases to 31%.145 Thus, during coronary vasodilation the coronary venous system may considerably modify myocardial perfusion. Furthermore, by affecting ventricular distensibility related to changes in myocardial blood volume,146 alterations in venous reactivity may also have an impact on diastolic cardiac function.

Isolated coronary venules dilate in response to an increase in flow.147 This flow-induced vasodilation is endothelium-dependent and mediated by the release of a nitrovasodilator. Endothelial disruption results in flow-induced constriction, suggesting that shear stress may directly act on the vascular smooth muscle.147 Whereas the additive effects of flow-induced dilatation and possibly myogenic relaxation of arterioles can maximise myocardial oxygen delivery during elevated the flow-induced venular dilatation may possibly contribute to a reduction in postcapillary resistance.

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Responses

  • Katrin Hahn
    When contraction of a myocardial segment is absent?
    2 years ago
  • Joey Martin
    What is phasic blood flow?
    2 months ago

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