Transmural Myocardial Perfusion

In the controversy about the mechanisms determining the high zero flow pressures and the further interpretation of coronary diastolic pressure flow relations, this paper takes a stand in favor of intramyocardial compliance as the primary cause of the high zero flow pressures. An attempt has been made to estimate the compliance distribution within the coronary circulation and to show the specific effect of intramyocardial compliance on arterial and venous pressure-flow relations. Since no data are available on the distensibility of coronary arterioles and capillaries, these data were taken from studies on mesenteric vessels. Based on these data, it is shown that, depending on the transmural pressure, smooth muscle tone may either increase or decrease arteriolar compliance. A compliance distribution has been proposed based on assumed pressure, volume, and distensibility distributions. For all but the venous division of the circulation, experimental data on volume could be found in the literature. Based on this compartmental analysis, it is predicted that overall intramyocardial compliance may exceed epicardial arterial compliance by a factor 45. The literature presenting functional evidence for intramyocardial compliance effects has been reviewed. Experimental results on venous outflow during long diastoles have been analyzed. Pf = 0 coronary pressure at zero flow, is higher when measured later in diastole. It is shown that this may be explained by charging of intramyocardial compliance in the period before flow ceases. The discrepancy between results on pressure-flow relations in the fully dilated bed and autoregulated bed are related to the differences in pressure, resistance, and compliance distributions.

Coronary diastolic pressure-flow relation and zero flow pressure explained on the basis of intramyocardial compliance.

In order to evaluate the functional characteristics of the intramyocardial capacitance vessels during prolonged diastole, we analyzed the response of coronary vein flow after stepwise changes of coronary artery pressure in anesthetized open-chest dogs by using our newly developed laser Doppler velocimeter with an optical fiber. The peripheral portion of the great cardiac vein was isolated and the optical fiber tip was inserted into the vessel. The left anterior descending coronary artery was cannulated and connected to a reservoir to regulate coronary perfusion pressure. Intracoronary adenosine administration was carried out to avoid any change in coronary vasomotor tone. After 15 seconds of occlusion of the perfusion route, the heart was arrested by pacing-off. Two seconds later, coronary perfusion pressure was increased stepwise to a preset target pressure. This procedure was repeated by changing target pressure at 4 (or 5) different pressure levels (31-105 mm Hg). The great cardiac vein flow became zero due to the cardiac arrest and remained at zero for a moment (dead time) after the initiation of reperfusion. Then the flow reappeared and increased with first order time delay. The presence of dead time indicates the existence of unstressed volume, and the first order time delay represents the product of resistance and capacitance. The unstressed volume with a minimal vasomotor tone for perfusion pressure of 60-90 mm Hg was 5.2 +/- 2.2 ml per 100 g left ventricle, which is comparable to coronary blood flow for several beats. The capacitance at perfusion pressure of 60-90 mm Hg was 0.08 +/- 0.04 ml/mm Hg per 100 g left ventricle, while that at low perfusion pressure (30-50 mm Hg) was 0.14 +/- 0.09 ml/mm Hg per 100 g left ventricle. These results indicate that the intramyocardial capacitance vessels have two functional components, and that the phasic nature of coronary vein flow is solely the result of the myocardial squeezing of the blood in the capacitance vessels.

Functional characteristics of intramyocardial capacitance vessels during diastole in the dog.

Recent experimental work has highlighted a number of complex issues relating to blood ow dynamics in the normal fetus, where the structure and function of the cardiovascular system di ers substantially from the normal adult or neonate. Neonates with congenital heart disease may also display quite complex haemodynamics due to a persistence of some features of the fetal circulation after birth, along with heart and vascular abnormalities that disturb normal blood ow patterns. For example, in pulmonary atresia with intact ventricular septum (PAIVS), the right ventricular out ow path fails to develop, while the combination of an underdeveloped right ventricle and profound coronary abnormalities may give rise to quite unusual coronary arterial ow patterns. This thesis employs two research tools that are ideal for clarifying the processes that govern haemodynamics in these contexts. The rst is computer modelling, in which cardiac and vascular variables and con guration can be directly manipulated in a simulated physiological system without ethical concern. The second is wave intensity analysis, which is a powerful technique for discerning the origin of pressure/ ow waves, as well as wave interactions, that occur at or between di erent vascular measurement sites. To enable investigation of a wide range of circulatory interactions in the perinatal period, this thesis describes computer models of the entire circulation for the normal fetus and neonate, these being derived from a model of the adult circulation that also provides an essential haemodynamic reference point. The normal fetal and neonatal models are adapted to form a model of PAIVS, which includes commonly occurring coronary abnormalities such as a stula connecting to the right ventricular cavity and an interruption of the normal aorto-coronary pathway. These `comprehensive' models contain all of the major functional and anatomical segments of the circulation, including one-dimensional (1D) representations of the arterial and venous networks, and lumped parameter (0D) representations of the heart, valves and microvascular beds. In combination with wave intensity analysis and available experimental data, the normal fetal model is used to further investigate the determinants of the distinctive pressure/ ow waveforms and wave intensity patterns in the pulmonary trunk, proximal branch pulmonary arteries and ductus arteriosus that have been observed in recent experimental studies in fetal lambs. Additionally, the fetal model is harnessed to investigate factors that contribute to a so-called fetal right-ventricular dominance, and to delineate the likely physical basis of mean aorto-pulmonary pressure di erences and a functional separation of the upper body and lower body circulations in the fetus. The model of neonatal PAIVS is then used to elucidate the determinants of coronary arterial blood ow patterns and regional myocardial perfusion in the presence or absence of coronary abnormalities, both before and after surgical opening of the right-ventricular out ow path. The potential for coronary collateral connections to provide protection against myocardial ischemia is also explored. The ndings of this thesis underscore the potential for both computer modelling and wave intensity analysis to provide insights into complex haemodynamic interactions that may occur normally or abnormally in the perinatal period.

Computer modelling and wave intensity analysis of perinatal cardiovascular function and dysfunction

In the present study, characteristics of the phasic flow pattern in the great cardiac vein and the mechanism of such pattern formation were investigated using a laser Doppler velocimeter with an optic fiber probe. The laser Doppler velocimeter allowed measurements of venous blood velocity under more physiological conditions than were possible with previous methods. Moreover, venous blood flow measurement in the great cardiac vein mirrors the effects of myocardial contraction on the venous flow more directly than does measurement in the coronary sinus. Thus, our method is considered very useful. Results obtained from the present study are as follows: 1) Measurement of the phasic flow in the great cardiac vein was made in 11 anesthetized dogs using our laser Doppler method. The blood velocity curve obtained in the great cardiac vein was always characterized by a prominent systolic flow wave (SFW). The mean value for the maximum velocities under control conditions in 11 cases was 40±13 cm/s. The blood velocity increased with the onset of left ventricular ejection and decreased gradually after the peak formation at mid- or late systole. — 2) Besides the above SFW, one or two small wave components were frequently observed during the atrial contraction period and/or during the isovolumic contraction phase. On the waveform during the atrial contraction period, two cases showed forward flow, while one case showed reverse flow. The small reverse flow waves during the isovolumic contraction phase were found in seven cases. — 3) Pharmacological interventions of dipyridamole and isoproterenol increased the maximum velocity. Compared with dipyridamole, isoproterenol accelerated the rate of rise in the SFW. — 4) No significant coronary venous flow was observed during the diastolic period prolonged by vagal nerve stimulation. However, after coronary vasodilator drugs were administered, there was a transient significant coronary venous flow during the prolonged diastole. This may be the overflow from the coronary capacitance vessels. — 5) During a reactive hyperemic response, the flow velocity of the great cardiac vein increased with the increment of the blood flow volume of the left anterior descending artery. However, its phasic change did not always correspond to that of intramyocardial pressure.

Paul D. Stein

Papers

Pulsatile aspects of coronary sinus blood flow in closed-chest dogs