Dynamics of coronary occlusion in the pathogenesis of myocardial infarction.

In most coronary artery stenoses in humans, lumen size decreases in response to acute vasoconstriction, reduced aortic pressure or passive collapse. Because the effects of vasoconstriction and plaque rupture with thrombus formation are additive, in some cases total cessation of flow may result from only minimal obstruction by thrombus. This hypothesis was investigated with use of a previously developed model of the coronary circulation in which the pressure drop across and flow through an arterial stenosis were determined by standard hemodynamic equations. The vessel wall was assumed to be composed of pliable and rigid sections, as is the case in most arterial stenoses in humans. The computer analysis was conducted for a rigid stenosis and for a dynamic stenosis in which proximal artery constriction and distal collapse were simulated. Plaque rupture with subsequent thrombus formation was simulated as a decrease in lumen area without effect on the arterial wall. Compared with a dynamic stenosis, a rigid stenosis required a significantly larger thrombus for vessel occlusion. Thrombus formation equal to the nonobstructed area of the lumen was required to occlude a rigid vessel; a 60% stenotic vessel required a 40% plaque rupture with thrombus formation for occlusion. However, for a dynamic stenosis, if vasoconstriction and passive collapse were simulated, small plaque ruptures led to vessel occlusion: a 60% stenotic vessel required only a 12% plaque rupture with thrombus formation for occlusion. This analysis indicates that even mild coronary lesions may be responsible for myocardial infarction, suggesting that vasomotion may be a very important element in the pathogenesis of most myocardial infarcts.

Balancing the circulation: theoretic optimization of pulmonary/systemic flow ratio in hypoplastic left heart syndrome.

OBJECTIVES: This study examined the effects of the pulmonary (QP)/systemic (QS) blood flow ratio (QP/QS) on systemic oxygen availability in neonates with hypoplastic left heart syndrome. BACKGROUND: The management of neonates with hypoplastic left heart syndrome is complex and controversial. Both before and after surgical palliation and before heart transplantation, a univentricle with parallel pulmonary and systemic circulations exists. It is generally assumed that balancing pulmonary and systemic blood flow is best to stabilize the circulation. METHODS: We developed a mathematical model that was based on the simple flow of oxygen uptake in the lungs and whole-body oxygen consumption to study the effect of varying the QP/QS ratio. An equation was derived that related the key variables of cardiac output, pulmonary venous oxygen saturation and the QP/QS ratio to systemic oxygen availability. RESULTS: The key findings are 1) as the QP/QS ratio increases, systemic oxygen availability increases initially, reaches a maximum and then decreases; 2) for maximal systemic oxygen availability, the optimal QP/QS ratio is < or = 1; 3) the optimal QP/QS ratio decreases as cardiac output or percent pulmonary venous oxygen saturation, or both, increase; 4) the critical range of QP/QS, where oxygen supply exceeds basal oxygen consumption, decreases as cardiac output and percent pulmonary venous oxygen saturation decrease; 5) the relation between oxygen availability and QP/QS is very steep when QP/QS approaches this critical value; and 6) the percent oxygen saturation of systemic venous blood is very low outside the critical range of QP/QS and high within the critical range. CONCLUSIONS: This analysis provides a theoretic basis for balancing both the pulmonary and systemic circulation and suggests that evaluating both systemic arterial and venous oxygen saturation may be a useful way to determine the relative pulmonary and systemic flows. When high systemic arterial and low systemic venous oxygen saturation are present, pulmonary blood flow should be decreased; conversely, when both low systemic arterial and venous oxygen saturation are present, more flow should be directed to the pulmonary circulation.

New concepts regarding constriction within a stenosis Influence of intraluminal pressure changes.

Morphologic and clinical studies clearly show that most human coronary lesions exhibit vasomotion. Variable ischemic thresholds, ischemia unrelated to workload, and variant angina further prove the presence of vasoconstriction in coronary artery disease. While vasoconstriction is important in the presentation of coronary artery disease, the unique type of contraction present in an arterial stenosis has been only recently examined. In normal large conduit arteries, the afterload opposing smooth muscle contraction is the intraluminal pressure, which remains relatively constant. In stenotic arteries, as the artery constricts, the pressure (or afterload) opposing smooth muscle shortening decreases, leading to exaggerated constriction and augmented arterial narrowing. Physiologically, this implies that a unique type of contraction ("heterotonic") occurs within an arterial stenosis. Clinically, this type of contraction might explain the exaggerated shortening observed within an arterial stenosis. It also suggests that stenotic pressure is an important variable in the pathophysiology and potential treatment of angina pectoris.

Alterations in diastolic ventricular interdependence due to myocardial infarction.

The pressure and volume in one ventricle can directly influence the pressure and volume in the other ventricle. Since this mechanical coupling depends on the anatomical structure of the heart, we postulated that disease states which alter regional ventricular compliance will alter the mechanical coupling between the ventricles. We examined this hypothesis in six dogs, each with a prior myocardial infarction involving solely the left ventricular free wall. The animals were sacrificed, the hearts removed and placed in cool cardioplegic solution. Balloons were inserted into each ventricle and the left and right pressure (dPl,dPr) and volume (dVl,dVr) changes (or transfer) caused by change to the pressure and volume of the other ventricle were recorded. In five additional experiments, acute changes in compliance were induced by injecting glutaraldehyde into the left ventricular free wall. The results of these experiments were compared to four control experiments. As compared to the control experiments, the transfer functions dPl/dPr, dPl/dVr, dPr/dVl, and dVr/dVl increased significantly (p less than 0.05) in the infarct and glutaraldehyde groups, while the transfer functions dVl/dPr, dVl/dVr, dPr/dPl and dVr/dPl were unaltered in the infarct and glutaraldehyde groups. The results of these studies show significant selective alteration in the mechanical coupling between the ventricles following left ventricular free wall infarction.

Model studies of the contribution of ventricular interdependence to the transient changes in ventricular function with respiratory efforts.

The effects of variations in intrathoracic pressure on left ventricular function were studied using a mathematical model of the circulation. The variations in intrathoracic pressure directly affect the left ventricular afterload, and indirectly alter left ventricular filling by changing the right ventricular volume. The decrease in intrathoracic pressure with sustained inspiratory efforts increased the left ventricular afterload and thus reduced the left ventricular stroke volume. Secondary to the reduction in stroke volume, the left ventricular end systolic and end diastolic volumes increased. Decreasing intrathoracic pressure also increased the systemic venous return, thereby increasing right ventricular volume. The model predicted that an enlarged right ventricular volume would, through diastolic ventricular interdependence, immediately reduce the left ventricular end diastolic volume (which in turn reduced the left ventricular stroke volume), while through systolic ventricular interdependence it would increase left ventricular stroke volume and reduce left ventricular end systolic volume. An increased right ventricular volume would also increase right ventricular stroke volume and after a delay of a few heart beats raise left ventricular end diastolic and stroke volumes. The net effect of respiratory variations in intrathoracic pressure on left ventricular function would be a combination of these effects. Thus on sustained inspiration the left ventricular stroke volume initially decreased (left ventricular afterload and diastolic interdependence secondary to the increase in right ventricular volume partly counteracted by the effects of systolic interdependence), followed by an increase as the increased venous return reached the left ventricle. The model indicated that the response to a forced expiratory effort was not simply the opposite of the inspiratory response, since the increase in intrathoracic pressure during a forced expiration is accompanied by increases in abdominal pressure. On sustained expiration the left ventricular stroke volume initially increased, with no significant initial change in end diastolic volume. The cardiovascular response to respiration is complex, and model studies can help to isolate and identify the various components involved.

Venous collapse and the respiratory variability in systemic venous return.

OBJECTIVE: Venous collapse limits systemic venous return, but its effects on beat to beat respiratory venous return variations are less well known. The aim of this study was to investigate the effects of venous collapse on respiratory variations in venous return. METHODS: A model of venous collapse which included both an increase in haemodynamic resistance to flow and an increase in vessel compliance was incorporated in a previously described cardiovascular model. Respiration was simulated by 5 mm Hg swings of intrathoracic pressure (PTH) at different mean pressures such that the abdominal vena cava and jugular vein were either fully collapsed (mean PTH -11 mm Hg), in the transition zone between collapse and distension (mean PTH -6 mm Hg), or fully distended (mean PTH 9 mm Hg). The mean and standard deviations over each respiratory cycle of the venous return volume (flow integral over heart cycle) and the abdominal vena caval volume were recorded. RESULTS: Different venous return volume variabilities in the three operating zones of the vena cava were identified: (1) reduced variability in the collapsed zone associated with the increased haemodynamic resistance [venous return 93(SD 6) ml, abdominal vena caval volume 30(3) ml. absolute right atrial pressure -6.3(1.1) mm Hg]; (2) increased variability in the transition zone [venous return 86(24) ml, abdominal vena caval volume 81(15) ml, right atrial pressure -2.2(0.8) mm Hg]; (3) low variability in the distended zone [venous return 42(11) ml, abdominal vena caval volume 120(2) ml, right atrial pressure 10.1(1.1) mm Hg]. The greater the change in compliance with collapse the greater the increase in flow variability in the transition zone; with no change in compliance there was no increased flow variability in the transition zone. CONCLUSIONS: The results suggest that venous collapse increases the respiratory variations in venous return in the transition zone. As venous return variations contribute to arterial pressure variations, the collapsible nature of the great veins may influence respiratory variations in systemic arterial pressure.

Contribution of each wall to biventricular function.

OBJECTIVE: Common muscle fibres encircle both ventricles and the ventricles share a common septal wall. This close anatomical association suggests that regional ischaemia and structural integrity may alter systolic function in both the right and the left ventricle. To examine this possibility, we investigated the contribution of each wall to biventricular function. METHODS: Isolated hearts, obtained from anaesthetised rabbits, were perfused with physiological salt solution under constant pressure. Balloons were placed in the right and left ventricles to measure isovolumetric pressure, and pressure-volume curves were obtained. In separate sets of experiments, the left ventricular free wall, right ventricular free wall, or septum was made ischaemic, incised, or injected with glutaraldehyde, respectively. Pressure-volume curves were obtained again. RESULTS: After left ventricular free wall ischaemia (n = 11), right ventricular developed pressure decreased significantly from 27.9(SD 8.9) to 14.1(6.6) mm Hg (p < 0.05), and remained depressed when the left ventricular free wall was further damaged by glutaraldehyde. Cutting the left ventricular free wall (n = 6) decreased right ventricular developed pressure from 28.9(8.6) to 17.8(4.8) mm Hg (p < 0.05), while reapproximating the left ventricular free wall by suturing re-established right ventricular developed pressure. After right ventricular free wall ischaemia (n = 7), right ventricular developed pressure decreased from 26.8(6.6) to 24.1(5.7) mm Hg (NS) and left ventricular developed pressure was unaltered. Cutting the right ventricular free wall (n = 7) had no effect on left ventricular developed pressure. Cutting the septum (n = 7) had no obvious influence on right ventricular developed pressure, but dramatically decreased left ventricular developed pressure from 79.2(55.2) to 43.7(32.2) mm Hg (p < 0.05). Injecting glutaraldehyde into the septum (n = 7) decreased both right and left ventricular developed pressures from 22.1(8.5) to 14.0(8.8) and from 78.2(50.5) to 47.9(37.9), respectively. CONCLUSIONS: The results show that the heart should be viewed as a mechanical syncytium. The left ventricular free wall plays a critical role in right ventricular systolic function and may help to explain the right ventricular response to left ventricular ischaemia. On the other hand, in the isolated heart preparation, right ventricular free wall ischaemia has only a minimal effect on left ventricular systolic developed pressure. Altering ventricular septal function affects both right and left ventricular systolic function.

Disassociation of intrinsic and haemodynamic responses in stenotic arteries.

OBJECTIVE: In stenotic arteries, constriction can decrease intraluminal pressure, which in turn can further decrease vessel size. Because of these pressure changes, the hypothesis that haemodynamic responses may be significantly different from intrinsic smooth muscle responses in stenotic arteries was tested. METHODS: In rabbits (n = 16), one iliac artery was denuded (stenotic), and the other iliac artery was untouched (hypercholesterolaemic). The rabbits were placed on a 2% cholesterol diet for three weeks. Iliac arteries from these and normal (n = 8) rabbits were removed and studied as rings or perfused segments. RESULTS: In arterial rings, maximal isometric tension in response to noradrenaline was significantly (p < 0.05) greater in hypercholesterolaemic [0.59(SEM 0.03) x 10(6) dynes.cm-2] and normal arteries 0.63(0.04) compared with stenotic arteries [0.28(0.04)]. Normal [EC50 = 6.99(0.07), -log(M)] and hypercholesterolaemic [EC50 = 7.00(0.12)] rings were more sensitive (p < 0.05) to noradrenaline than stenotic rings [EC50 = 6.49(0.24)]. All arterial rings vasodilated in response to glyceryl trinitrate, and changes in isometric tension occurred over a 1000-fold change in noradrenaline or glyceryl trinitrate concentration. In normal and hypercholesterolaemic arteries, flow was unaltered even at the highest noradrenaline concentration. In stenotic arteries, noradrenaline decreased distal pressure from 76.9(5.4) to 24.3(7.3) mm Hg (p < 0.05) and flow from 17.9(1.6) to 6.4(1.8) ml.min-1 (p < 0.05). After noradrenaline decreased flow, glyceryl trinitrate did not always successfully vasodilate the stenotic arteries and thereby re-establish flow. Lastly, in stenotic arteries, most of the haemodynamic response occurred at one incremental dose of noradrenaline or glyceryl trinitrate. CONCLUSION: Fundamentally different haemodynamic responses occur in stenotic v normal and hypercholesterolaemic arteries. As the intrinsic smooth muscle responses (from the stenotic rings) are weaker, the augmented responses in whole stenotic segments are probably related to the intraluminal pressure changes.

Do overlapping vessels protect against canine right ventricular infarction after right coronary artery occlusion?

The severity of ischaemia in the left ventricle from total coronary occlusion is modified by retrograde blood flow through collateral or overlapping vessels, but whether that is true for the right ventricle is not known. The consequences and extent of ischaemic damage from occlusion of the right coronary artery were studied in anaesthetised dogs. In group 1 (n = 9), the right coronary artery alone was occluded; in group 2 (n = 8), the right coronary artery and overlapping vessels from the left anterior descending and circumflex coronary arteries were occluded. Occlusion for 2 h caused right ventricular end diastolic pressure to increase by 2.8(SEM 0.4) mm Hg in group 1 (p less than 0.05) and by 1.9(0.5) mm Hg in group 2 (p less than 0.05). Fractional shortening in the ischaemic zone became akinetic in group 1: 12.0(1.4)% v 0.1(1.6)%; p less than 0.05; and dyskinetic in group 2: 12.1(2.1)% v -1.2(0.9)%; p less than 0.05. In both groups, fractional shortening remained depressed during the ensuing 2 h of reperfusion. The incidence of right ventricular free wall necrosis was 56% in group 1 but 100% in group 2 (p = 0.082). The area of necrosis, expressed as a percentage of the area at risk, was 13.9(6.6)% in group 1 in contrast to 66.9(4.5)% in group 2 (p less than 0.05). Both groups had equal involvement of the subendocardial and subepicardial layers. We conclude that ligating epicardial overlapping vessels in addition to the right coronary artery produces a larger area of right ventricular free wall necrosis.

Effects of increased pericardial pressure on the coupling between the ventricles.

STUDY OBJECTIVE: The mechanical coupling between the ventricles occurs directly through the myocardium (ventricular-ventricular coupling) and indirectly through the pericardium (ventricular-pericardial-ventricular coupling). We postulated that the magnitude of ventricular-pericardial-ventricular coupling would increase at high pericardial pressures, while ventricular-ventricular coupling would be unaltered. DESIGN: Canine hearts were removed and placed in cold cardioplegic solution. Balloons were inserted into each ventricle and the left and right ventricular pressure (dP1, dPr) and volume (dV1, dVr) changes caused by increasing the pressure and volume of the other ventricle and by increasing pericardial pressure (dPp) were measured. EXPERIMENTAL MATERIALS: Hearts from 10 random source dogs, weight 12.5-18 kg, were used. MEASUREMENT AND MAIN RESULTS: At control pericardial pressure levels, the magnitude of the pericardial-ventricular interactions was greater than the ventricular-ventricular interactions: dP1/dPp was significantly greater than dP1/dPr, at 0.71 (SEM 0.04), n = 6, v 0.18 (0.03), p less than 0.01, and dV1/dPp was significantly greater than dV1/dPr, at -0.83 (0.09) v -0.24 (0.06), p less than 0.05. Raising the pericardial pressure increased the mechanical coupling between the ventricles: dP1/dPr approximately, dV1/dPr approximately, dPr/dP1 approximately, and dVr/dP1 approximately increased significantly (p less than 0.05) by 0.48 (0.03), 0.67 (0.13), 0.38 (0.05), and 0.61 (0.09) respectively. This increased coupling occurred through pericardial pressure changes. If pericardial pressure was maintained constant, the coupling between the ventricles was unaltered. This same pattern was observed in four in situ experiments. For these experiments, at the raised pericardial pressure levels, dP1/dPr increased, from 0.51 (0.03) to 0.79 (0.01), p less than 0.05, if pericardial pressure was allowed to vary, but was unaltered with a constant pericardial pressure, at 0.42 (0.03) v 0.44 (0.04), p greater than 0.5. CONCLUSIONS: Ventricular interdependence was increased with raised pericardial pressure and this increased coupling was due primarily to an increased ventricular-pericardial-ventricular coupling. This increased coupling may help to explain the paradoxical pulse observed in cardiac tamponade.

Differential effects of positive end expiratory pressure and cardiac tamponade on left-right ventricular mechanical function in the dog.

OBJECTIVE: The aim was to examine the hypothesis that an increased coupling occurs between the ventricles during tamponade via a ventricular-pericardial-ventricular interaction, but that ventricular coupling would be unaltered or reduced with positive end expiratory pressure (PEEP). METHODS: An in situ arrested, canine heart preparation was used. Changes in left and right ventricular pressure (dPl, dPr) and volume (dVl, dVr) caused by increasing the volume of the other ventricle were measured at normal and at matched levels of raised pericardial pressures (Pp) caused by 20 cm H2O PEEP and by tamponade. RESULTS: With PEEP, the coupling between the ventricles was unaltered when compared to control. With tamponade, dPl/dPr, dVl/dPr, dPr/dPl, and dVr/dPl increased significantly (p less than 0.05) by 0.21 (SEM 0.03, unitless), 0.45(0.04) ml.mm Hg-1, 0.18(0.03), and 0.28(0.04) ml.mm Hg-1 respectively. CONCLUSIONS: Augmented ventricular interdependence occurs during tamponade but not with PEEP, which may help to explain the different haemodynamic patterns observed under these conditions.

Importance of endothelial function in stenotic haemodynamic responses.

STUDY OBJECTIVE: The aim was to examine endothelium mediated flow dependence in a dynamic stenosis. DESIGN: The coronary circulation was modelled as a proximal compliant stenosis and a fixed distal resistance. Pressures and flow were calculated using standard haemodynamic equations. Within the stenosis, the vessel wall was composed of normal and rigid sections, and the normal section dilated proportionally with flow. From this theoretical analysis, three perfusion pressures (150, 100, and 75 mm Hg) and two distal resistances (high and low) were examined. MAIN RESULTS: In a stenotic artery (93% area reduction) with high flow dependence, decreasing distal resistance increased flow substantially. At 75 mm Hg perfusion pressure, flow increased from 40.8 to 81.6 ml.min-1. With moderate flow dependence, flow increases were attenuated. Without flow dependence, flow increases were smaller, and at low perfusion pressure, flow paradoxically decreased (39.0 to 0.0 ml.min-1) when distal resistance decreased. Vasoconstriction responses with and without flow dependence were analysed. In a stenotic artery, vasoconstrictors caused a concentration dependent decrease in flow. Without flow dependence, the flow dose-response curve was shifted to the left: a lower level of arterial vasoconstriction resulted in a greater flow decrease. CONCLUSIONS: The theoretical analysis shows significantly different flow responses to decreasing distal resistance and to vasoconstriction depending on endothelial function. Endothelial dysfunction may be important in the pathophysiology of angina pectoris.

Estimation of left ventricular elastance without altering preload or afterload in the conscious dog.

OBJECTIVE: The aim was to determine the slope (EES) of the left ventricular end systolic pressure-volume line (ESPVL) without altering preload or afterload in conscious dogs. METHODS: Dogs (n = 10) were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions, and to measure left ventricular pressure using a micromanometer. Studies were performed one to two weeks after instrumentation while the animals were conscious. ESPVL was determined from variably loaded left ventricular pressure-volume (P-V) loops generated by the vena caval occlusion. Contractile state was increased by intravenous dobutamine (8 micrograms.kg-1 x min-1) and decreased by intravenous verapamil (10 mg) given after autonomic blockade. From a single normally ejecting beat, we calculated EES-single beat (mm Hg.ml-1) as peak isovolumetric pressure (Pmax) minus end systolic pressure divided by stroke volume. Sunagawa's technique was used to estimate Pmax by fitting the pressure during the isovolumetric contraction and relaxation as: P(t) = 1/2 X Piso[1-cos(omega t+c)]+LVEDP, where Piso = peak isovolumetric developed pressure, LVEDP = left ventricular end diastolic pressure, c = constant accounting for variations in phase angle, and omega = 2 pi/T in which T is duration of contraction. RESULTS: After dobutamine, EES increased, from 8.9(SEM 0.8) to 12.5(1.0) mm Hg.ml-1 (p < 0.05), and EES-single beat increased from 9.1(0.9) to 12.0(1.4) mm Hg.ml-1 (p < 0.05). Conversely, after verapamil, EES decreased, from 11.1(1.2) to 6.3(1.1) mm Hg.ml-1, (p < 0.05), and EES-single beat also decreased, from 9.6(1.0) to 7.3(1.2) mm Hg.ml-1, (p < 0.05). CONCLUSIONS: EES calculated from one beat is similar to EES determined from variably loaded left ventricular loops and responds appropriately to inotropic stimulation. This technique provides a reasonable method to calculate EES from left ventricular pressure and stroke volume without altering preload or afterload.

Alterations in left ventricular compliance due to changes in right ventricular volume, pressure and compliance.

Because of ventricular interdependence, part of the measured left ventricular diastolic pressure can be attributed to the right ventricle. Therefore, we examined the hypothesis that left ventricular diastolic properties are modified by alterations in right ventricular compliance and pressure even without a change in right ventricular volume. To examine this hypothesis, the hearts were removed from six dogs, the coronary arteries perfused with cool cardioplegic solution, and the hearts submerged in cool cardioplegic solution. Balloons were inserted into each ventricle. Left ventricular pressure-volume curves were recorded and approximated by an exponential equation. With no fluid in the right ventricular balloon (control), the exponential coefficient and constant were 0.038 (SD 0.004) ml-1 and 2.38(0.75) mm Hg respectively. With right ventricular pressure held constant at 20 mm Hg, the exponential coefficient and constant were 0.035(0.002) ml-1 and 3.71(1.64) mm Hg (p less than 0.05 v control constant), respectively. With a fixed right ventricular volume, the exponential coefficient and constant were significantly different (p less than 0.05 v control values) at 0.040(0.006) ml-1 and 2.81(0.96) mm Hg, respectively. After decreasing right ventricular free wall compliance by injecting glutaraldehyde into the right coronary artery, the exponential coefficient and constant were significantly different (p less than 0.01 v control values) at 0.058(0.010) ml-1 and 1.86(0.60) mm Hg, respectively. Thus, even with a constant right ventricular pressure or volume, a significant upward shift in the left ventricular pressure-volume relation occurred. Decreasing right ventricular free wall compliance further increased left ventricular pressure. The results of these studies indicate that the diastolic properties of the left ventricle can be modified by changes in right ventricular pressure and compliance even without a change right ventricular volume. Thus indices of left ventricular diastolic properties may be altered by changes in the characteristics of the right ventricle.

Effect of acute cardiac tamponade on left ventricular pressure-volume relations in anaesthetised dogs.

STUDY OBJECTIVE: The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN: Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation, the left ventricular dP/dtmax-end diastolic volume relation, and the left ventricular stroke work-end diastolic volume relation during acute cardiac tamponade in dogs. EXPERIMENTAL MATERIAL: In eight pentobarbitone anaesthetised dogs (15.7-24.8 kg), transducer tipped and volume impedance catheters were positioned in the left ventricle. Through a median sternotomy incision, a pericardial catheter was inserted to produce varying stages of cardiac tamponade. By the use of transient bicaval occlusions, variably loaded pressure-volume loops were recorded. MEASUREMENTS AND RESULTS: Incremental tamponade reduced mean arterial pressure from 105(SEM 3) to 89(2) mm Hg (mild tamponade), 75(2) mm Hg (moderate tamponade), and 59(10) mm Hg (severe tamponade). The slope of the end systolic pressure-volume relation was 6.3(1.2) mm Hg.ml-1 at baseline and increased slightly to 7.7(1.8), 8.5(1.3), and 9.2(1.5) mm Hg.ml-1 with the progressive levels of tamponade (NS). The role of autonomic reflexes was assessed by repeating the tamponade sequence after beta adrenergic blockade with 10 mg of metoprolol intravenously. The slope of the end systolic pressure-volume relation was reduced by metoprolol, at 4.9(1.0) mm Hg.ml-1 (p less than 0.01), but was not significantly altered by the sequence of tamponade following beta blockade [5.6(0.9), 6.0(1.0), and 5.5(7.0) mm Hg.ml-1, respectively (NS)]. Neither were changes found indicative of depressed contractile function with progressive tamponade in the slopes of the left ventricular dP/dtmax-end diastolic volume and stroke work-end diastolic volume relations. CONCLUSIONS: Left ventricular contractility was not altered during acute cardiac tamponade in an anaesthetised, closed chest canine model. Depressed left ventricular contractile function was not responsible for the observed haemodynamic deterioration.

Comparative significance in systolic ventricular interaction.

STUDY OBJECTIVE: The aim was to measure the systolic coupling between the ventricles and to determine the relative importance of ventricular interaction in the pressure development of each ventricle. DESIGN: Acute studies were done in dogs to measure the changes in right and left ventricular pressures (dPr, dPl) caused by sudden changes in left ventricular pressure (dPl') with release of an aortic constriction, and sudden changes in right ventricular pressure (dPr') with release of a pulmonary artery constriction, respectively. The instantaneous cross talk gain [dPr/dPl' (Klr) or dPl/dPr' (Krl)] was calculated during the ejection phase. The potential systolic pressure generated by the contralateral ventricle was evaluated as the cross talk gain multiplied by the contralateral systolic developed pressure. EXPERIMENTAL MATERIAL: Studies were done in eight random source dogs (12-18 kg), anaesthetised with sodium pentobarbitone. MEASUREMENTS AND MAIN RESULTS: The maximal Klr was lower than the maximal Krl, at 0.09 (SD 0.05) v 0.25 (0.06), and the mean Klr also was lower than the mean Krl, at 0.04 (0.02) v 0.10 (0.03), p less than 0.05. The potential right ventricular pressures developed by the left ventricle [maximum 10.3(5.6), mean 4.8(2.7) mm Hg] were not significantly different from the potential left ventricular pressures developed by the right ventricle [maximum 8.8(2.7), mean 3.4(0.7) mm Hg]. However, the ratio between the potential transmitted pressure and the measured developed pressure was greater in the right ventricle [maximum 39.0(21.1), mean 17.8(8.9)%] than in the left ventricle [maximum 11.1(7.1)%, p less than 0.05; mean 3.9(1.5)%, p less than 0.01]. This suggests that about 20-40% of the right ventricular systolic pressure may result from the left ventricle and about 4-10% of the left ventricular systolic pressure may result from right ventricle. CONCLUSIONS: Although the pressure coupling was greater in right to left ventricular interaction, right ventricular pressure generation may be more dependent on the left ventricle. Systolic ventricular interaction may be more important for right ventricular systolic function. Further, the parameters of right ventricular systolic function currently used may be considerably affected by the left ventricle.

Variable non-linearity in end systolic pressure-volume relationships results from interaction between end diastolic and developed pressure-volume relations.

OBJECTIVE: The aim was to determine the contributions of diastolic pressure to the shape of the relationship of total systolic left ventricular pressure with volume (pressure-volume relationship). STUDY DESIGN: The pressure-volume relationship was approximated (by least squares fit) to a parabola P = aV2 + bV + C. Non-linearity was indicated by values "a" significantly different from zero. Negative values indicated concavity to the volume axis, positive values convexity to the volume axis. MATERIALS: Langendorff perfused rabbit hearts (n = 8) with intraventricular balloon were used. Balloon pressure was measured for varying balloon volumes. RESULTS: The total systolic pressure-volume relationship was concave towards the volume axis at 2.4 mM extracellular calcium ions concentrations ([Cae++]) a = -47.2 (SD 5.4), p less than 0.05. It was nearly linear at [Cae++] = 0.6 mM; a = -0.8(5.8), p greater than 0.05. It was convex at [Cae++] = 0.3 mM; a = 25.3(4.0), p less than 0.01. The diastolic pressure-volume relationship was always convex: a = 30.1(6.7), 33.5(7.6), 42.2(6.6) for [Cae++] = 2.4, 0.6, and 0.3 mM respectively. When these diastolic values were subtracted from the total pressures, pressure-volume curves for developed pressure were obtained which were always concave: a = -76.9(10.2), -33.5(3.7), -16.3(2.9) for [Cae++] = 2.4, 0.6, and 0.3 mM. CONCLUSIONS: The true systolic pressure-volume relationship of the left ventricle is not linear but concave to the volume axis. The slope is therefore variable and not an index of contractility. Apparently linearity or convexity is due to inappropriate addition of the diastolic pressure-volume properties.

The left ventricle affects the duration of right ventricular ejection.

OBJECTIVE: The aim was to determine if rapid changes in left ventricular pressure can acutely alter right ventricular systolic pressure and thus influence the length of right ventricular ejection. METHODS: The experiments were performed in six open chest anaesthetised dogs, weight 18-25.5 kg. Left and right ventricular pressures and pulmonary blood flow were recorded continuously as left ventricular pressure was abruptly decreased by opening a shunt in systole. From these data, the pressure and flow changes and the duration of right ventricular ejection were determined. RESULTS: Opening the left ventricular shunt caused left ventricular pressure to fall from 94.1(SD 10.5) to 62.6(11.3) mm Hg (p < 0.01), right ventricular pressure to fall from 30.3(4.6) to 27.0(3.6) mm Hg (p < 0.01), and pulmonary flow to fall from 69.5(14.2) to 57.5(13.9) ml.s-1. The duration of right ventricular ejection, determined from pulmonary flow, also decreased from 192.7(22.7) to 157.2(18.7) ms (p < 0.05) and was significantly related to the length of left ventricular systole. Time between end diastole and peak negative dP/dt decreased for both left and right ventricle. Left and right ventricular time intervals were related before (r = 0.99) and after (r = 0.75) opening the shunt. CONCLUSIONS: The duration of right ventricular ejection was decreased by a sudden decrease in left ventricular afterload and was significantly related to the length of left ventricular systole. The duration of right ventricular ejection may be coupled with left ventricular contraction through ventricular interdependence.

Validation of local venous sampling within the at risk left anterior descending artery vascular bed in the canine left ventricle.

The validity of using blood sampled from the anterior interventricular vein (AIV), anatomically located within the myocardium perfused by the left anterior descending (LAD) coronary artery, to represent venous drainage originating from the LAD vascular territory was studied in eight anaesthetised, open chest dogs. The LAD was cannulated and perfused from a blood reservoir isolated from the systemic circulation. To determine the presence of blood from non-LAD sources that appears in the AIV sample, 51Cr-labelled red blood cells were injected into the left atrium and distributed in the systemic circulation while the LAD was perfused by non-radioactive blood. The percentage spillover of red blood cells from non-LAD sources into the AIV drainage was determined under control, reduced LAD flow, ischaemia, and reperfusion conditions as 100 X (AIV chromium content/arterial chromium content). Spillover of red blood cells into AIV blood samples averaged only 1.5(1.3)% under control conditions and increased insignificantly to 8.6(3.5)% during reduced LAD flow. During ischaemia red blood cells in AIV blood increased insignificantly to 98.3(5.0)% but decreased to 1.9(1.3)% after reperfusion. Studies in five dogs with microspheres showed that a portion of this admixture from non-LAD sources originated from precapillary nutritional collateral or overlapping blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular coupling via the pericardium: normal versus tamponade.

OBJECTIVE: The aim was to examine how regional variations in pericardial pressure affect the mechanical coupling between the ventricles. METHODS: Canine hearts from 14 dogs (14.5-18 kg) were removed and placed in cold cardioplegia solution. Balloons were inserted into the left and right ventricles and the atria. Pericardial pressure over the left ventricle (Pclv) and the right ventricle (Pcrv) was measured with thin balloon catheters. Ventricular and pericardial pressures were measured, and ventricular and pericardial coupling was calculated, under control conditions and with increases in pericardial tension and fluid. RESULTS: At baseline, regional differences in pericardial pressure occurred [Pclv > Pcrv, 4.0(SD 0.9) v 2.9(0.6) mm Hg, p < 0.05]. Ventricular coupling via the pericardium was defined as delta Pclv/delta Pcrv for right ventricular volume increases and delta Pcrv/delta Pclv for left ventricular volume increases. This ratio increased more after increasing right ventricular volume than after increasing left ventricular volume [delta Pclv/delta Pcrv > delta Pcrv/delta Pclv, 1.14(0.33) v 0.51(0.15), p < 0.05]. Increasing the pericardial tension by clamping the pericardium increased pericardial pressures, yet did not alter the regional variations in pressure [Pclv > Pcrv, 8.4(2.2) v 6.4(2.5) mm Hg, p < 0.05] or pericardial coupling [delta Pclv/delta Pcrv > delta Pclv/delta Pcrv, 1.18(0.46) v 0.54(0.16), p < 0.05]. In contrast, creating a mild tamponade increased pericardial pressures, eliminated regional differences in pressure, and altered the coupling between ventricles [delta Pclv/delta Pcrv approximately delta Pclv/delta Pcrv, 0.95(0.11) v 1.05(0.08), p = NS]. These regional differences in pericardial pressure might have a geometrical basis. In four in vivo canine experiments using cine magnetic resonance, the short axis radius of curvature for the right ventricle was greater than for the left ventricle [38.3(4.4) mm v 29.2(3.8) mm, p < 0.05]. CONCLUSIONS: The pericardium partially protects right ventricular filling: regional differences in pericardial pressure normally occurred with lower pericardial pressure over the right ventricle, and left to right ventricular coupling was less. This protection of right ventricular filling was lost with even a small pericardial effusion.