Evaluation of myocardial oxygen extraction dynamics in syndrome X by continuous measurement of coronary sinus oxygen saturation and its relation to clinical features]

We investigated the relation of myocardial oxygen extraction dynamics to pathophysiology and clinical features in syndrome X. In patients with syndrome X who underwent cardiac catheterization, coronary sinus oxygen saturation (n = 21) during rapid atrial pacing loading was continuously measured using a fiberoptic catheter system, and global and regional left ventricular function (n = 14) was evaluated before and immediately after pacing loading. Results were as follows: 1) In 5 of 21 patients with syndrome X, coronary sinus oxygen saturation during pacing loading fell less than 5% below the baseline without any impairments of global and regional left ventricular function. 2) In 16 patients with syndrome X, coronary sinus oxygen saturation during the pacing loading continuously fell over 5% below the baseline accompanied by impairment of both global and regional left ventricular function. The decrease in regional wall motion of the left ventricle was mainly observed in the apical area. These findings imply that changes in myocardial oxygen extraction dynamics in syndrome X during rapid atrial pacing may show the extent of a patchy area where myocardial oxygen demand-supply imbalance occurs due to coronary microcirculatory disturbances.     

Visualization of subendocardial myocardial ischemia with myocardial contrast echocardiography in humans

Previous studies indicate the degree of myocardial echo contrast enhancement may be related to regional myocardial perfusion. In this study, myocardial contrast echocardiography was used to characterize changes in the transmural myocardial blood flow distribution that were provoked by rapid atrial pacing in 11 patients with one-vessel coronary artery disease. Ten patients without coronary artery disease served as controls. Myocardial contrast echocardiography was performed by intracoronary injection of 2 ml hand-agitated amidotrizoate sodium meglumine (Urografin-76) and by imaging a short-axis view of the left ventricle with two-dimensional echocardiography before and during injection of the contrast agent. The two-dimensional echocardiographic images at end diastole, before and after injection of the contrast agent, were digitized off-line into a 512 x 512 pixel matrix with 256 gray levels/pixel to quantify the degree of the enhancement of the peak gray level after injection. Transmural myocardial blood flow distribution was evaluated by measuring the ratio of the enhanced gray level in the endocardial half (endo) to that in the epicardial half (epi) (endo:epi gray level ratio) in the anteroseptal, posterolateral, and inferior segments before and just after rapid atrial pacing in each patient. In patients without coronary artery disease, there were no differences in the endo:epi gray level ratio between any of the three segments both before and after pacing. Mean values of the three segments were 0.95 +/- 0.08 before pacing and 0.90 +/- 0.13 after pacing, respectively. In contrast, in patients with coronary artery disease, the endo:epi gray level ratio for the segment supplied with stenotic coronary artery decreased after pacing (0.40 +/- 0.21 vs. 0.93 +/- 0.18, p less than 0.01), probably reflecting subendocardial myocardial ischemia, whereas that for the segment supplied with nonstenotic coronary artery remained unchanged (0.88 +/- 0.20 vs. 0.99 +/- 0.23, NS). Thus, changes in transmural myocardial blood flow distribution with rapid pacing, which may be due to transient subendocardial ischemia, are visualized with myocardial contrast echocardiography.     

Myocardial surface PO2--an indicator of myocardial tissue oxygenation?

The validity of myocardial surface tissue PO2 (PtO2) as a reliable indicator of transmural myocardial tissue oxygenation was studied in six anaesthetised, open chest pigs. Epicardial surface PtO2 was correlated with other variables of myocardial tissue oxygenation such as regional blood flow, coronary venous PO2, O2 saturation, PCO2 and regional myocardial lactate extraction. The study design was based on an experimental model in which the effects of a pacing induced tachycardia on tissue oxygenation of ischaemic and normally supplied myocardium were measured. Two platinum multiwire surface electrodes were placed on the epicardium, on the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (CX). The LAD was constricted to reduce mean surface PtO2 in the LAD area to about 50% of its baseline value. This did not affect surface PtO2 in the CX area. The reduction of surface PtO2 in the LAD area was associated with decreases in coronary venous PO2 and O2 saturation and with increases in coronary venous lactate and PCO2. Subendocardial regional blood flow and the subendocardial to subepicardial flow ratio were significantly lower than in the CX area. Increasing the heart rate by pacing (+45 beats.min-1) led to an increased degree of ischaemia as shown by fall in surface PtO2 in the LAD area to values around zero kPa, by marked increase in coronary venous lactate and PCO2, by reduction in total (-10%) and subendocardial (-40%) LAD flow and by deterioration of the subendocardial to subepicardial flow ratio. The increased degree of ischaemia was not accompanied by an increase in O2 extraction. The marked decrease in surface PtO2 occurred in spite of a slight increase in the subepicardial regional blood flow (+10%); thus the increase in O2 delivery was not sufficient to meet the increase in O2 demand. Total flow was increased by 27% in the CX area without changes in the subendocardial to subepicardial flow ratio and in the surface PtO2 values. When pacing was stopped, surface values of PtO2 in the LAD area returned to prepacing values, as did lactate extraction and coronary venous PCO2. Clear and close relationships with surface PtO2 were found for regional lactate extraction, coronary venous PCO2 and the normalised subendocardial RBF. Poor or no correlations were found for the normalised subepicardial regional blood flow, the coronary venous O2 saturation and the absolute values of subendocardial and subepicardial regional blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia.

Studies were performed to determine if intervention with hypertonic mannitol and intraaortic balloon counterpulsation increases regional myocardial blood flow during acute myocardial ischemia. Anesthetized dogs on right heart bypass were studied. Heart rate was kept constant by atrial pacing. Myocardial ischemia was provided by ligating the proximal left anterior descending coronary artery for 12 minute periods. Infusion of hypertonic mannitol begun immediately after ligation increased coronary blood flow to the ischemic area by 36 +/- 9.0% (standard error) (P less than 0.01) and to the nonischemic left ventricle by 21 +/- 8.8% (P less than 0.05) as compared with flow in the same regions during the control coronary ligation. Intraaortic balloon counterpulsation begun immediately after ligation increased regional coronary flow to the ischemic region by 20 +/- 8.4% (P less than 0.05) but did not significantly alter flow to the nonischemic left ventricle as compared with levels during the control ligation. Combined intraaortic counterpulsation and hypertonic mannitol increased coronary flow to the ischemic region by 46 +/- 13% (P less than 0.02) and to the nonischemic left ventricle by 59 +/- 22% (P less than 0.05) as compared with flow during occlusion of the left anterior descending artery with mannitol alone. The data demonstrate that both hypertonic mannitol and intraaortic counterpulsation increase left ventricular ischemic regional flow and that combined hypertonic mannitol and intraaortic balloon counterpulsation provide a greater increase in regional coronary blood flow to both the ischemic and nonischemic regions of the left ventricle than mannitol alone.     

Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 +/- 0.5 g (mean +/- SEM) in the right ventricle and 10.5 +/- 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 +/- 0.7 g in the right ventricle and 5.2 +/- 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 +/- 0.06 and 0.28 +/- 0.05 in the right and left ventricles, respectively (p less than 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 +/- 0.04 in the right ventricle and 0.32 +/- 0.06 in the left ventricle (p less than 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.     

Influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact dogs with prolonged coronary artery occlusion.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance in awake, intact, unsedated dogs with myocardial infarction resulting from chronic occlusion of the proximal left anterior descending coronary artery was studied. tmannitol given to increase serum osmolality 20 mOsm increased regional myocardial blood flow to that portion of the left ventricle supplied by the occluded left anterior descending coronary artery by 22 +/- 2.8% (1.06 +/- 0.19 to 1.36 +/- 0.23 ml/min with g-1) without changing the inner:outer wall flow ratio. Mannitol also significantly increased regional myocardial blood flow to other areas of the left ventricle and the ventricular septum. Mean aortic pressure, maximal LV dP/dt, LV dP/dt/P, and cardiac output also increased significantly after mannitol. Thus hypertonic mannitol increases regional myocardial blood flow and ventricular performance in the awake, unsedated dog with prolonged occlusion of the proximal left anterior descending coronary artery. The increase in regional myocardial blood flow after mannitol under these circumstances probably is at least in part secondary to the increase in blood pressure and contractility. The increases in regional myocardial blood flow after mannitol in this study are less impressive than those that have been previously reported in the setting of either no myocardial ischaemia or acute myocardial ischaemia; this is probably due to the vasodilatation that chronic myocardial ischaemia itself produces in the canine heart.     

No effect of coronary perfusion on regional myocardial function within the autoregulatory range in pigs. Evidence against the Gregg phenomenon

BACKGROUND. The hypothesis that increases in coronary perfusion increase ventricular performance independently from providing enhanced oxygen supply ("Gregg phenomenon") remains controversial. METHODS AND RESULTS. To study the physiological significance of changes in coronary perfusion on global and regional myocardial function in situ, the left anterior descending coronary artery of isoflurane-anesthetized swine was cannulated, and perfusion was varied. In one group of swine (n = 5), coronary arterial pressure was increased in four steps from 88 +/- 11 to 186 +/- 11 mm Hg by increasing the speed of the pump circuit providing coronary blood flow. No changes in left ventricular end-diastolic pressure, peak pressure, or maximum left ventricular dP/dt were observed. Subendocardial blood flow (by radiolabeled microspheres) increased from 0.96 +/- 0.27 to 2.04 +/- 0.73 ml/min/g without any increase in systolic wall thickening (by sonomicrometry) or myocardial oxygen consumption of the anterior myocardium. In a second group of swine (n = 8), coronary arterial pressure was kept constant and coronary blood flow was increased stepwise by intracoronary adenosine infusion. End-diastolic pressure, peak pressure, and maximum left ventricular dP/dt remained unchanged when coronary blood flow increased from 21.7 +/- 9.8 to 93.8 +/- 34.1 ml/min. Subendocardial blood flow increased from 0.89 +/- 0.26 to 3.28 +/- 1.02 ml/min/g, again without any increase in systolic wall thickening (45.6 +/- 8.6 versus 42.6 +/- 9.8%) and myocardial oxygen consumption (5.75 +/- 1.18 versus 5.87 +/- 1.67 ml/min/100 g). In a third group of swine (n = 10), coronary arterial pressure was lowered by intracoronary adenosine infusion during constant coronary inflow. Left ventricular hemodynamics remained unchanged. With a decrease in coronary arterial pressure from 130 +/- 25 to 71 +/- 14 mm Hg, no decreases in subendocardial blood flow and systolic wall thickening were observed. Only when coronary arterial pressure was further reduced to 57 +/- 13 mm Hg did systolic wall thickening fall to 25.7 +/- 9.9% (control, 31.1 +/- 11.1%), associated with a decrease in subendocardial blood flow from 1.17 +/- 0.39 to 0.87 +/- 0.52 ml/min/g. CONCLUSIONS. Thus, the Gregg phenomenon plays no significant role within or above the autoregulatory pressure-flow range normally seen in anesthetized swine in situ.     

Effects of altered site of electrical activation on myocardial performance during inotropic stimulation

The effects of altering the site of electrical activation on responses to isoproterenol (ISO) and treadmill exercise were examined in mongrel dogs instrumented for long-term measurement of left ventricular pressure, left ventricular dP/dt, coronary blood flow, cardiac output, left ventricular diameters, and mean arterial pressure and O2 content in the coronary sinus and aorta. During spontaneous rhythm, 0.2 micrograms/kg/min ISO increased heart rate by 90 +/- 7 beats/min, left ventricular dP/dt by 2479 +/- 301 mm Hg/sec, cardiac output by 3.5 +/- 0.9 liters/min, coronary blood flow by 30.4 +/- 3.9 ml/min, and myocardial oxygen consumption (MVO2) by 3.91 +/- 0.84 ml/min. During right atrial pacing at 193 +/- 7 beats/min, the effects of ISO were not different from the effects during spontaneous rhythm, with the exception of a lesser increase in coronary blood flow and lesser reductions in coronary resistance and left ventricular end-diastolic diameter and pressure. During right ventricular pacing at an identical rate, ISO increased left ventricular dP/dt (1140 +/- 158 mm Hg/sec) and cardiac output (2.2 +/- 0.5 liters/min) significantly less (p less than .025) than during either sinus rhythm or right atrial pacing, while MVO2 rose to a higher value. During right ventricular pacing the changes in mean arterial pressure and left ventricular end-diastolic diameters with ISO were not significantly different from those during right atrial pacing. Treadmill exercise induced significantly smaller (p less than .025) increases in left ventricular dP/dt during right ventricular pacing as compared with during either right atrial pacing or sinus rhythm, while MVO2 rose to a higher value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diurnal changes in coronary blood flow in conscious dogs

The purpose of the present study was to evaluate potential diurnal changes in resting coronary blood flow under conditions of comparable myocardial oxygen requirements. We studied 21 conscious, resting dogs instrumented for the measurement of coronary flow, left ventricular pressure, and regional myocardial segment length. Recordings were taken in the early morning and late afternoon. In the afternoon, left circumflex coronary blood flow was 12.8% higher than in the morning, without detectable changes in the major hemodynamic determinants of myocardial oxygen consumption, i.e., heart rate, left ventricular pressure, peak positive dP/dt, end-diastolic regional myocardial dimension, and regional myocardial stroke work. These results are consistent with a circadian variation of coronary vascular tone accompanied by compensatory alteration in myocardial oxygen extraction and may have clinical relevance, since the coronary vascular tone may change dynamically in patients with critical coronary stenosis.     

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of ventricular asynchrony on myocardial perfusion

Asynchronous depolarization and contraction sequence, secondary to intraventricular conduction defects or to permanent right ventricular apical pacing, is associated with adverse effects that may be clinically evident in the failing heart. Experimental and clinical studies have suggested that asynchronous ventricular contraction deteriorates left ventricular performance and induces unfavourable left ventricular remodelling. Although such contraction does not appear to affect resting coronary artery blood flow, it increases endomyocardial pressure during diastole and decreases regional myocardial perfusion in the interventricular septum. The magnitude of these effects may correlate with the duration of the asynchrony. Despite these detrimental effects, there is no evidence that ventricular asynchrony reduces collateral myocardial blood flow, myocardial oxygen consumption or cardiac efficiency, neither in patients with normal coronary arteries, nor in patients with coronary artery disease. Furthermore, in patients with acute ischaemic syndromes, ventricular asynchrony exerts a neutral effect on the ischaemic myocardium. Cardiac resynchronization therapy improves left ventricular systolic and diastolic function without an increase in myocardial oxygen consumption or energy cost. This therapy may decrease the inhomogeneity in regional oxidative metabolism, myocardial perfusion and cardiac efficiency. Further experimental and clinical studies are needed on this area.     

Effect of hyper- and hypovolaemia on regional myocardial oxygen consumption

STUDY OBJECTIVE - The purpose of the investigation was to study the effect of preload on coronary blood flow and myocardial oxygen consumption in subendocardial and subepicardial regions of left ventricular free wall. DESIGN - Ventricular volume in anaesthetised open chest dogs was altered over a range of 20% to produce hypovolaemia (10-15% exsanguination) or hypervolaemia (colloid infusion), allowing measurements of regional blood flow and oxygen consumption with varying preloads. beta Adrenergic blockade was used to limit changes in inotropy, and heart rate was kept constant by pacing at 150 beats.min-1. SUBJECTS - 9 mongrel dogs of either sex weighing 24.9 (SEM 4.1) kg were studied. MEASUREMENTS and RESULTS - Left ventricular volume was calculated from ultrasonic measurements of long and short axis end diastolic diameters and wall thickness. Regional myocardial blood flow was estimated using radioactive microspheres, and oxygen consumption in each region was determined from microspectrophotometric measurements of oxygen saturations in small arteries and veins. Hypervolaemia increased subepicardial blood flow from 66.8(6.9) (normovolaemic) to 114.1(13.5) ml.min-1.100 g-1, and regional oxygen consumption from 4.08(0.57) to 6.44(1.08) ml.min-1.100 g-1. Values in the subendocardium were similar, except for oxygen consumption, which increased less than in the subepicardium. Left ventricular end diastolic volume, pressure, and output were each increased in hypervolaemia, but not dP/dt and systolic aortic pressure. Hypovolaemia reduced blood pressures without reducing end diastolic volume. CONCLUSIONS - Augmented flow work produced by increased preload (even in the absence of changes in pressure work) increases myocardial oxygen supply equally in the subepicardium and the subendocardium, while oxygen extraction and consumption are preferentially augmented in the subepicardium.     

Regional myocardial volume alterations induced by brief repeated coronary occlusion in conscious dogs

The purpose of this study was to evaluate whether brief repeated coronary occlusions induce changes in regional myocardial geometry at rest. Five conscious dogs were instrumented for the measurement of subendocardial segment length and transmural wall thickness in the ischemic area, subendocardial segment length in the normally perfused area, coronary flow and left ventricular pressure. After recovery from surgery, 180 (mean) 2 min coronary occlusions were given over a period of 20 days. The heart rate at rest, left ventricular peak systolic and end-diastolic pressures and peak positive first derivative of left ventricular pressure (dP/dt) remained unchanged throughout the experiment. In the normal area, the end-diastolic segment length at rest did not change significantly. By contrast, in the ischemic area, at 14 days after the initiation of repeated coronary occlusion, the end-diastolic regional cross-sectional area (product of segment length and wall thickness) at rest had increased by 9.7% (p less than 0.05); thereafter it decreased to 6.5% (p less than 0.05) above the value at rest before repeated occlusion despite an additional 6 days of coronary occlusions. At 10 days after the interruption of repeated occlusion, this value had regressed to 4.3% (p = NS) above control. These findings suggest the occurrence of regional myocardial hypertrophy confined to the ischemic area in response to the periodic ischemic stimulus.     

Abnormal subendocardial blood flow in pressure overload hypertrophy is associated with pacing-induced subendocardial dysfunction

To detect the functional significance of subendocardial hypoperfusion in the pressure-overloaded left ventricle, we studied subendocardial and subepicardial function and subendocardial and subepicardial blood flow simultaneously in seven dogs with left ventricular hypertrophy (left ventricle/body weight ratio, 7.2 g/kg) produced by chronic aortic banding. Seven normal dogs served as controls. Subendocardial and subepicardial segment lengths were measured by ultrasonic dimension gauges, and myocardial blood flow was measured with radioactive microspheres. Atrial pacing (180-200 beats/min for 5 minutes) was used to produce a chronotropic stress. In dogs with left ventricular hypertrophy, the subendocardial blood flow failed to increase during pacing compared with the baseline state (1.21 +/- 0.17 vs. 1.22 +/- 0.17 ml/min/g). Subendocardial shortening fraction deteriorated with pacing stress (before pacing, 30.6 +/- 3.9%; after pacing, 24.2 +/- 3.7%; p less than 0.001). In controls, subendocardial blood flow increased from 1.32 +/- 0.19 to 1.80 +/- 0.19 ml/min/g during pacing, and shortening fraction was preserved (before pacing, 25.5 +/- 3.9%; after pacing, 25.9 +/- 3.3%). Subepicardial blood flow in dogs with hypertrophy increased from 1.54 +/- 0.24 to 2.32 +/- 0.34 ml/min/g, and subepicardial shortening fraction was maintained (before pacing, 10.4 +/- 1.0%; after pacing, 10.5 +/- 1.2%) as it was in controls (subepicardial blood flow, from 1.27 +/- 0.18 to 2.12 +/- 0.17 ml/min/g; shortening fraction, from 16.6 +/- 2.5% to 15.5 +/- 2.2%). We conclude that, with pacing stress in pressure-overload hypertrophy, subendocardial blood flow failed to increase. This abnormality corresponded with a deterioration in subendocardial contractile function.     

Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine

We studied the effects of rapid atrial pacing during the final 10 minutes of a 70-minute, 31% reduction in coronary blood flow in anesthetized swine to understand the significance of apparent metabolic improvements during the initial 60 minutes of segmental ischemia. Within 5-10 minutes of ischemia, subendocardial phosphocreatine (PCr) and ATP were depleted to 47% and 63% of control, respectively; lactate accumulated within the subendocardium to 300% of control; and net arteriovenous lactate production occurred. Despite continued ischemia and no significant changes in the external determinants of myocardial oxygen consumption, by 60 minutes subendocardial PCr and lactate contents returned to near control levels and there was net arteriovenous lactate consumption. Ischemic left ventricular wall thickening and ATP levels remained depressed throughout the experiment. Atrial pacing during the final 10 minutes of ischemia again resulted in depletion of PCr and lactate production. Since the myocardium was capable of hydrolyzing PCr in response to atrial pacing at 60 minutes of ischemia, we conclude it was capable of hydrolyzing PCr during the period of constant ischemia when instead it was accumulating PCr. We propose the ischemic myocardium downregulates regional energy requirements below blood flow-limited rates of energy production during ischemia. This appears to be an active adaptation to ischemia and not a result of passive damage or cellular injury.     

Doppler echocardiographic evaluation of pulmonary artery flow after modified Fontan operation: importance of atrial contraction

Doppler echocardiography was used to evaluate blood flow in the pulmonary artery in 14 patients 2 to 42 months (mean (SD) 17 (12) months) after a modified Fontan operation incorporating a direct atriopulmonary anastomosis. Preoperatively six patients had tricuspid atresia, six had a double inlet left ventricle, and two had pulmonary atresia with an intact ventricular septum. The postoperative rhythm was sinus in 11 patients, junctional in one, ventricular pacing in one, and atrioventricular sequential pacing in one. In one patient the Doppler trace was unsatisfactory for analysis. In all patients forward flow in the pulmonary artery had biphasic peaks related to both atrial and ventricular contraction. The mean (SD) peak flow velocity that was synchronous with atrial contraction was 80 (30) cm/s and that synchronous with ventricular contraction was 74 (23) cm/s. The atrial contribution to total pulmonary artery flow, assessed by velocity-time integrals, varied between 22% and 73% (mean (SD) 45 (14)%). In patients with tricuspid atresia the mean (SD) peak flow velocity with atrial contraction was 90 (27) cm/s and that with ventricular contraction was mean (SD) 68 (24) cm/s. In patients with double inlet left ventricle the mean (SD) peak flow velocity was 67 (36) cm/s with atrial contraction and 80 (25) cm/s with ventricular contraction. The atrial contribution to total pulmonary blood flow in patients with tricuspid atresia was significantly higher (53 (11)%) than in those with double inlet left ventricle (37 (14)%). Pulmonary artery flow after modified Fontan operation was biphasic and was related to both atrial and ventricular contraction. The atrial contribution to pulmonary blood flow is greater in patients with tricuspid atresia than in those with a double inlet left ventricle. The mechanism of the second peak related to ventricular contraction is unknown.     

Doppler echocardiographic evaluation of pulmonary artery flow after modified Fontan operation: importance of atrial contraction.

Doppler echocardiography was used to evaluate blood flow in the pulmonary artery in 14 patients 2 to 42 months (mean (SD) 17 (12) months) after a modified Fontan operation incorporating a direct atriopulmonary anastomosis. Preoperatively six patients had tricuspid atresia, six had a double inlet left ventricle, and two had pulmonary atresia with an intact ventricular septum. The postoperative rhythm was sinus in 11 patients, junctional in one, ventricular pacing in one, and atrioventricular sequential pacing in one. In one patient the Doppler trace was unsatisfactory for analysis. In all patients forward flow in the pulmonary artery had biphasic peaks related to both atrial and ventricular contraction. The mean (SD) peak flow velocity that was synchronous with atrial contraction was 80 (30) cm/s and that synchronous with ventricular contraction was 74 (23) cm/s. The atrial contribution to total pulmonary artery flow, assessed by velocity-time integrals, varied between 22% and 73% (mean (SD) 45 (14)%). In patients with tricuspid atresia the mean (SD) peak flow velocity with atrial contraction was 90 (27) cm/s and that with ventricular contraction was mean (SD) 68 (24) cm/s. In patients with double inlet left ventricle the mean (SD) peak flow velocity was 67 (36) cm/s with atrial contraction and 80 (25) cm/s with ventricular contraction. The atrial contribution to total pulmonary blood flow in patients with tricuspid atresia was significantly higher (53 (11)%) than in those with double inlet left ventricle (37 (14)%). Pulmonary artery flow after modified Fontan operation was biphasic and was related to both atrial and ventricular contraction. The atrial contribution to pulmonary blood flow is greater in patients with tricuspid atresia than in those with a double inlet left ventricle. The mechanism of the second peak related to ventricular contraction is unknown.     

Hemodynamic and coronary effects of intravenous verapamil in coronary insufficiency

Verapamil inhibits calcium influx through the slow calcium canals. The coronary an haemodynamic effects of intravenous Verapamil were studied in 8 patients with chronic coronary insufficiency documented by coronary arteriography. The following measurements were made in spontaneous rhythm and during atrial pacing under basal conditions and 10 minutes after intravenous Verapamil (0.10 to 0.17 mg/kg) relayed with a continuous infusion of 5 x 10(-3) mg/Kg/mn: heart rate, cardiac output, left ventricularr pressure (Millar 5 F micromanometer), femoral artery pressure, coronary sinus flow by continuous thermodilution, oxygen and lactate concentrations in arterial and arterio-venous oxygen difference, and index of myocardial oxygen consumption and the coefficient of lactate extraction were then calculated. The coronary and haemodynamic effects of atrial pacing were similar before and after Verapamil at a given rate. Left ventricula end diastolic pressure decreased, cardiac output and total systemic resistance were unchanged, dP/dt max increased but to a lesser degree after Verapamil (P less than 0.05). Coronary arterio-venous oxygen difference decreased after Verapamil. The coronary and haemodynamic effects of Verapamil were similar in spontaneous rhythm and during atrial pacing. In spontaneous rhythm, the heart rate and left ventricular end diastolic pressure increased. In spontaneous and paced rhythm, femoral artery pressure, total systemic resistance and dP/dt max decreased. Cardiac output remained the same. Myocardial oxygen consumption decreased mainly because of a reduced coronary arterio-venous oxygen difference and because of unchanged coronary flow in spontaneous rhythm oxygen consumption seems to have a favourable effect on the myocardial energy equilibrium as shown by the increased coefficient of lactate extraction during atrial pacing after Verapamil. This study shows the negative inotropic and arterial vasodilator effects of Verapamil to be responsible for the reduced myocardial oxygen consumption. It also caused coronary artery vasodilation.     

Transmural distribution of myocardial blood flow during systole in the awake dog.

This study was designed to quantitate transmural myocardial blood flow when coronary arterial inflow was limited to systole and during the subsequent reactive hyperemic response. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flowmeters and pneumatic occluders on the left circumflex coronary artery. Intermittent coronary perfusion, confined to the interval of left ventricular systole or an equivalent period during diastole, was effected by an R wave-triggered solenoid valve connected to the occluder. To measure regional myocardial blood flow we injected radionuclide-labeled microspheres, 7-10 mum in diameter, into the left atrium. When arterial inflow was limited to systole, flow was normal in the subepicardial layers and was decreased as a linear function of tissue depth in the subendocardial layers. When coronary arterial inflow was limited to an equivalent interval in diastole, the transmural distribution of flow was uniform. When coronary flow was confirmed to systole for more than 20 seconds, the blood flow debt incurred elicited a reactive hyperemia similar to that following a total occlusion of equivalent blood flow debt. However, regional myocardial blood flow during the peak of reactive hyperemia following systolic perfusion was preferentially directed to the subendocardium, where underperfusion was most marked, whereas reactive hyperemia flow following a total occlusion of equivalent blood flow debt was distributed more evenly across the left ventricular wall. Thus, when coronary inflow was limited to systole, ventricular contraction produced a transmural gradient in myocardial blood flow resulting in subendocardial underperfusion.     

Thallium-201 scintigraphy in complete left bundle branch block

Nineteen symptomatic patients with left bundle branch block (LBBB) were examined by thallium-201 (TI-201) exercise scintigraphy and selective coronary arteriography. All elicited significant anteroseptal perfusion defects in the exercise scintigrams, but in only 4 was coronary artery disease (CAD) involving the left anterior descending coronary artery present. To further elucidate the effect of LBBB on septal TI-201 uptake in the absence of CAD, TI-201 scintigrams combined with regional myocardial blood flow measurements using radioactive microspheres were carried out in 7 dogs during right atrial and right ventricular pacing (LBBB in the ECG) at similar heart rates. During right atrial pacing, TI-201 uptake was homogeneous in the entire left ventricle, as were tissue flows. During right ventricular pacing, TI-201 activity was reduced to 69% of maximal TI-201 activity within the septum, whereas it averaged 90% in the lateral wall (p less than 0.05) in 6 dogs. Correspondingly, regional myocardial blood flow was lower within the septum as compared with that in the lateral wall, averaging 89 and 120 ml/min/100 g, respectively (p less than 0.005). In 1 dog, normal TI-201 distribution and tissue flows were found in both studies. Thus, symptomatic patients with LBBB may elicit abnormal TI-201 exercise scintigrams, suggesting anteroseptal ischemia despite normal coronary arteries. The electrical induction of LBBB in dogs results, in most instances, in a comparable reduction in septal TI-201 uptake associated with diminished septal blood flow. Therefore, exercise-induced septal perfusion defects in the presence of LBBB do not necessarily indicate CAD even in symptomatic patients, but may reflect functional ischemia due to asynchronous septal contraction.