Mechanisms of myocardium-coronary vessel interaction

The mechanisms by which the contracting myocardium exerts extravascular forces (intramyocardial pressure, IMP) on coronary blood vessels and by which it affects the coronary flow remain incompletely understood. Several myocardium-vessel interaction (MVI) mechanisms have been proposed, but none can account for all the major flow features. In the present study, we hypothesized that only a specific combination of MVI mechanisms can account for all observed coronary flow features. Three basic interaction mechanisms (time-varying elasticity, myocardial shortening-induced intracellular pressure, and ventricular cavity-induced extracellular pressure) and their combinations were analyzed based on physical principles (conservation of mass and force equilibrium) in a realistic data-based vascular network. Mechanical properties of both vessel wall and myocardium were coupled through stress analysis to simulate the response of vessels to internal blood pressure and external (myocardial) mechanical loading. Predictions of transmural dynamic vascular pressure, diameter, and flow velocity were determined under each MVI mechanism and compared with reported data. The results show that none of the three basic mechanisms alone can account for the measured data. Only the combined effect of the cavity-induced extracellular pressure and the shortening-induced intramyocyte pressure provides good agreement with the majority of measurements. These findings have important implications for elucidating the physical basis of IMP and for understanding coronary phasic flow and coronary artery and microcirculatory disease.

Wall thickness of coronary vessels varies transmurally in the LV but not the RV: implications for local stress distribution

Since the right and left ventricles (RV and LV) function under different loading conditions, it is not surprising that they differ in their mechanics (intramyocardial pressure), structure, and metabolism; such differences may also contribute to differences in the coronary vessel wall. Our hypothesis is that intima-media thickness (IMT), IMT-to-radius (IMT-to-R) ratio, and vessel wall stress vary transmurally in the LV, much more than in the RV. Five normal Yorkshire swine were used in this study. The major coronary arteries were cannulated through the aorta and perfusion fixed with 6.25% glutaraldehyde and casted with a catalyzed silicone-elastomer solution. Arterial and venous vessels were obtained from different transmural locations of the RV and LV, processed for histological analysis, and measured with an imaging software. A larger transmural gradient was found for IMT, IMT-to-R ratio, and diastolic circumferential stress in vessels from the LV than the nearly zero transmural slope in the RV. The IMT of arterial vessels in the LV showed a slope of 0.7 ± 0.5 compared with 0.3 ± 0.3 of arterial vessels in the RV ( P ≤ 0.05). The slope for venous vessels in the LV was 0.14 ± 0.14 vs. 0.06 ± 0.05 in the RV. The present data reflect the local structure-function relation, where the significant gradient in intramyocardial pressure in the LV is associated with a significant gradient of IMT and IMT-to-R ratio, unlike the RV. This has important implications for local adaptation of transmural loading on the vessel wall and vascular remodeling when the loading is perturbed in cardiac hypertrophy or heart failure.

Image-Based Modeling of Blood Flow in Human Coronary Arteries With and Without Bypass Grafts During Rest and Simulated Exercise

The number of patients with coronary artery disease continues to rise, with approximately 469,000 coronary bypass procedures in 2005 alone [1]. A priori knowledge of the flow features within the coronary vascular system could prove useful in predicting flow changes due to coronary bypass surgery. Image-based modeling and 3-D computational simulations could be used to compute flow and pressure in a patient-specific manner. However, modeling coronary flow requires knowledge of the intramyocardial pressure that compresses coronary vessels, resulting in decreased flow in systole and increased flow in diastole. Left ventricular pressure can provide an estimate to intramyocardial pressure, but the aortic pressure and left ventricular pressure must be coupled in systole when the aortic valve is open. Previously, we have developed a method to couple a lumped-parameter heart model to the inlet of a 3-D model to compute aortic and ventricular pressure [2]. In this study, we use the lumped-parameter heart model and computational fluid dynamics to calculate flow dynamics in a patient model with coronary artery bypass grafts.

Cross-Talk Between Cardiac Muscle and Coronary Vasculature

The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+transient, which is followed by an increase in Ca2+sensitivity and higher muscle contractility (Gregg effect). Thickening of the shortening cardiac muscle takes place at the expense of the vascular volume, which causes build-up of intracellular pressure. The intracellular pressure counteracts the tension generated by the contractile apparatus, leading to lower net force. Therefore, cardiac muscle contraction is augmented when vascular emptying is facilitated. During autoregulation, the microvasculature is protected against volume changes, and the Gregg effect is negligible. However, the effect is present in the right ventricle, as well as in pathological conditions with ineffective autoregulation. The beneficial effect of vascular emptying may be reduced in the presence of a stenosis. Thus cardiac contraction affects vascular diameters thereby reducing coronary inflow and enhancing venous outflow. Emptying of the vasculature, however, enhances muscle contraction. The extracellular matrix exerts its effect mainly on cardiac properties rather than on the cross-talk between cardiac muscle and coronary circulation.

Influence of Transmyocardial Laser Revascularization (TMLR) on Regional Cardiac Function and Metabolism in an Isolated Hemoperfused Working Pig Heart

The mechanism of an indirect revascularization in ischemic myocardium by transmyocardial laser revascularization (TMLR) is not yet fully understood. An improvement of clinical symptoms caused by TMLR is reported in many clinical trials with patients in which a direct revascularization is not possible. An increase of myocardial perfusion through laser channels is doubtful, because the myocardial pressure in the wall is higher than in the cavum. Therefore we measured the local cardiac function (intramyocardial pressure, wall thickness, pressure-length curves) and acute metabolic changes (tissue lactate content, tissue pO2) in ischemic and non-ischemic regions before and after TMLR in isolated hemoperfused pig hearts. An isolated heart was chosen because it enabled us to separate coronary flow from flow through ventricular channels. The ischemia was induced by coronary occlusion or microembolization (eight hearts each). It should be noted that microembolization leads to conditions which are more comparable with those found in patients selected for TMLR. In the isolated working heart, the coronary perfusion can be controlled independently from perfusion through the ventricular cavum. Under the ischemic conditions mentioned above, we observed that the intramyocardial pressure in the ischemic region decreased below the left ventricular pressure, so one premise for indirect perfusion was met. TMLR after microembolization led to a significant improvement of regional cardiac work and the tissue oxygen pressure. These acute effects demonstrate the possibility of functional and metabolic amelioration by TMLR after ischemia induced by microembolization in an isolated hemoperfused pig heart.

Intramyocardial pressure measurements in the stage 18 embryonic chick heart

Intramyocardial pressure (IMP) and ventricular pressure (VP) were measured in the trabeculating heart of the stage 18 chick embryo (3 days of incubation). Pressure was measured at several locations across the ventricle using a fluid-filled servo-null system. Maximum systolic and minimum diastolic IMP tended to be greater in the dorsal wall than in the ventral wall, but transmural distributions of peak active (maximum minus minimum) IMP were similar in both walls. Peak active IMP near midwall was similar to peak active VP, but peak active IMP in the subepicardial and subendocardial layers was four to five times larger. These results suggest that the passive stiffness of the dorsal wall is greater than that of the ventral wall and that during contraction the inner and outer layers of both walls generate more contractile force and/or become less permeable to flow than the middle part of the wall. Measured pressures likely correspond to regional variations in wall stress that may influence morphogenesis and function in the embryonic heart.

Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia

On the hypothesis that coronary sinus occlusion (CSO) may reduce myocardial ischemia, we examined the effects of CSO on coronary collateral blood flow and on the distribution of regional myocardial blood flow (RMBF) in dogs. Thirty-eight anesthetized dogs underwent occlusion of the left anterior descending coronary artery with or without CSO and intact vasomotor tone. We measured RMBF and intramyocardial pressure (IMP) in the subendocardium (Endo) and subepicardium (Epi) separately. With intact vasomotor tone, CSO during ischemia significantly increased RMBF in the ischemic region (IR), particularly in Endo from 0.17 ± 0.03 to 0.33 ± 0.05 ml · min−1· g−1( P < 0.05), and increased the Endo/Epi from 0.59 ± 0.10 to 1.15 ± 0.15 ( P < 0.01). These effects of CSO were partially abolished by adenosine. However, the Endo/Epi was still increased from 0.90 ± 0.13 to 2.09 ± 0.30 ( P < 0.01). The changes in RMBF in IR were significantly correlated with the peak CS pressure during CSO. The Endo/Epi of IMP in IR was significantly decreased during CSO. In conclusion, CSO potentially enhances coronary collateral flow, and preserves the ischemic myocardium, especially in Endo.

Correlation of ventricular mechanosensory neurite activity with myocardial sensory field deformation

The mechanosensory activity generated by ventricular epicardial sensory neurites associated with afferent axons in thoracic sympathetic nerves was correlated with sensory field deformation (long axis, short axis, and transmural dimension changes), regional intramyocardial pressure, and ventricular chamber pressure in anesthetized dogs. Ventricular mechanosensory neurites generated activity that correlated best with strain developed along either the long or short axis of their epicardial sensory fields in most instances. Activity did not correlate normally to local wall thickness or to regional wall or chamber pressure development in most cases. During premature ventricular contractions, the activity generated by these sensory neurites correlated best with maximum strain developed along at least one sensory field epicardial vector. Identified sensory neurites were also activated by local application of the chemical bradykinin (10 μM) or by local ischemia. These data indicate that the activity generated by most ischemia-sensitive ventricular epicardial sensory neurites associated with afferent axons in sympathetic nerves is dependent on not only their local chemical milieu but on local mechanical deformation along at least one epicardial vector of their sensory fields.

Compression of intramyocardial arterioles during cardiac contraction is attenuated by accompanying venules

It was calculated how cardiac contraction influences the luminal cross-sectional area of a maximally dilated coronary arteriole (37-micron inner diameter at a pressure of 35 mmHg) that is accompanied by two equal venules (45-micron inner diameter at a pressure of 17 mmHg), forming a so-called "triad." It was found that, during a contraction with 14% cardiac muscle shortening, arteriolar area is virtually unaffected (increase of 4%) at the expense of a large (55%) decrease in venular area. For comparison, the areas of an unaccompanied arteriole and an unaccompanied venule were calculated to be reduced by 45 and 36%, respectively, demonstrating the "protective effect" on accompanied arterioles in a triad. During contraction, the overall resistance of a system consisting of one arteriole in series with two parallel venules of equal length was calculated to increase about twice as much for nonaccompanied vessels (resistance increases by a factor of 2.8) than for vessels in a triad arrangement (resistance increased by a factor of 1.4). The calculations show that the extravascular (intramyocardial) pressure, which determines vascular area, is not an independent variable as in the intramyocardial pump and waterfall models but depends on the vascular "loading" conditions. Thus the small venular pressure together with the large venular compliance causes the extravascular pressure to remain low during contraction, thereby protecting the stiff arteriole at high pressure. We conclude that the triad arrangement of intramyocardial coronary vessels attenuates the increase in coronary resistance during cardiac contraction and thus has an important functional advantage.