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.     

Left atrial and left ventricular diastolic function during acute myocardial ischaemia.

OBJECTIVE--To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. DESIGN--Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. PATIENTS--20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. RESULTS--The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). CONCLUSIONS--Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.     

Influence of frequency of atrial contraction on coronary blood flow and ventricular performance in the conscious dog with myocardial infarction.

The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.     

Nitroprusside infusion in experimental acute myocardial infarction with systemic hypertension: effects on systemic hemodynamics and regional myocardial blood flows

The effects of graded doses of nitroprusside on regional myocardial blood flow were studied in awake, acutely hypertensive dogs with acute myocardial infarction. Acute systemic hypertension was produced by infusing a mixture of norepinephrine and epinephrine for 80 minutes after coronary artery occlusion. The increase in aortic pressure produced by catecholamine infusion was accompanied by increases in heart rate, left ventricular (LV) end-diastolic pressure, first derivative of LV pressure (dP/dt), dP/dt at an LV developed pressure of 50 mm Hg (dP/dt/P) and pressure-rate product, but total peripheral vascular resistance did not change significantly. Two graded doses of nitroprusside were then infused, each for 25 minutes, beginning 30 minutes after the onset of coronary artery occlusion. The smaller dose of nitroprusside returned aortic pressure to control levels and significantly reduced total peripheral vascular resistance and LV end-diastolic pressure, but did not affect cardiac output, heart rate, LV dP/dt, dP/dt/P and pressure-rate product. Regional blood flow increased to both the ischemic and normal myocardium. The larger dose of nitroprusside further reduced aortic pressure and total peripheral vascular resistance and LV end-diastolic pressure and significantly increased heart rate and cardiac output. However, LV dP/dt, dP/dt/P and pressure-rate product remained unchanged. Regional blood flow to normal myocardium increased, but the increase in ischemic endocardial blood flow produced by the smaller dose of nitroprusside was no longer significant when the larger dose was administered. These changes were not produced by administration of normal saline solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left atrial and left ventricular diastolic function during acute myocardial ischaemia

Objective—To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia.Design—Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery.Patients—20 patients with isolated disease of the left anterior descending artery and normal left ventricular function.Results—The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by −37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by −11%).Conclusions—Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.     

Alterations in regional myocardial blood flow after nitroprusside and nitroglycerin in patients with and without significant coronary artery disease

To evaluate vasodilator-induced redistribution of regional myocardial blood flow, intravenous sodium nitroprusside and nitroglycerin were administered in doses producing matched reductions (15%) in mean arterial pressure at constant heart rate. Anterior left ventricular great cardiac vein blood flow (thermodilution) was measured in 14 patients without angiographic anterior collateral supply. Global coronary sinus blood flow remained constant with both nitroprusside and nitroglycerin administration, despite significant reductions in mean arterial pressure. However, nitroglycerin reduced great vein flow by 25 +/- 17% and nitroprusside by 10 +/- 16% (p less than 0.01). Subgroup analysis indicated that the nitroglycerin-nitroprusside regional blood flow differences were more pronounced in patients without significant left anterior descending coronary artery narrowing. Neither vasodilator produced significant differences in arterial-coronary sinus oxygen or lactate contents, calculated myocardial oxygen consumption, left ventricular dP/dt, or electrocardiographic or clinical signs of myocardial ischemia. Despite qualitatively similar hemodynamic effects, comparisons of vasodilator-induced relative reductions in normally supplied anterior left ventricular regional coronary blood flow suggest a mechanism of the reported beneficial effects of nitroglycerin on potentially ischemic myocardial regions.     

Differences in ischaemic dysfunction after gradual and abrupt coronary occlusion: effects on isovolumic relaxation

The effects of both gradual and abrupt coronary occlusion on regional wall function (sonomicrometry) and left ventricular relaxation were studied in the intact dog heart. The ischaemic dysfunction observed in the two interventions as assessed by pressure-length loops showed considerably different patterns. The regional ischaemia after abrupt occlusion of the left anterior descending coronary artery was characterised by a bulge during isovolumic relaxation in contrast to the pattern observed during gradual occlusion, which was characterised chiefly by early systolic lengthening and post-systolic shortening. The effect of regional dysfunction on left ventricular relaxation was evaluated using peak negative dP/dt and tau, the time constant of isovolumic pressure decline. Abrupt occlusion had a more profound effect on relaxation than did gradual occlusion, though there were no significant changes in either pressure or flow derived indices of systolic ventricular function with abrupt occlusion of the left anterior descending artery. Two distinct patterns of regional dysfunction were produced at zero coronary flow depending on the time course of the occlusion. The regional dysfunction observed during abrupt occlusion may in part be explained by the mechanical effect of abrupt cessation of coronary flow, which in turn influences relaxation. With gradual occlusion tau was less affected even though substantial regional dysfunction was observed. This may reflect the development of collateral flow. Thus the patterns of regional dysfunction and ventricular relaxation depend on the time course of ischaemia.     

Left atrial function in acute transient left ventricular ischemia produced during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery

Left atrial (LA) function was studied in 32 patients during percutaneous transluminal coronary angioplasty of the proximal left anterior descending artery with a dual micromanometer positioned transseptally in the left atrium and in the left ventricle. In 10 patients LA and left ventricular (LV) cineangiography was performed 30 minutes before percutaneous transluminal coronary angioplasty and 30 seconds after the occlusion of the left anterior descending coronary artery. Thirty seconds after left anterior descending occlusion, LV peak systolic pressure decreased from 135 +/- 12 to 106 +/- 9 mm Hg (p less than 0.05) and LV maximum dP/dt decreased from 1,634 +/- 136 to 1,137 +/- 127 mm Hg/s (p less than 0.01). Simultaneously, LA mean pressure increased from 11 +/- 2 to 29 +/- 1 mm Hg (p 177 +/- 13 to 381 +/- 21 mm Hg (p less than 0.001). There was a difference between LV end-diastolic pressure and LA mean pressure of 1.5 mm Hg at rest and 7.8 mm Hg during ischemia and LA pulse pressure increased from 16 +/- 3 to 26 +/- 3 mm Hg (p less than 0.05) together with increase of LA A and V waves peak pressure. LV stroke volume index decreased from 46 +/- 5 to 43 +/- 3 ml/m2 (difference not significant). The LA maximal volume increased from 18 +/- 2 to 29 +/- 3 ml/m2 (p less than 0.001). LA volume before LA contraction increased from 29 +/- 2 to 54 +/- 3 ml/m2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen consumption and coronary reactivity in postischemic myocardium

Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10-minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6 +/- 2.6 vs. 18.4 +/- 3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve in response to adenosine was unaltered (63 +/- 9 vs. 70 +/- 15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio = 474 +/- 78% vs. 322 +/- 74%; p less than 0.05) and duration (57 +/- 9.1 vs. 35 +/- 4.5 seconds; p less than 0.05), while the peak flow response was unchanged (57 +/- 6.8 vs. 60 +/- 7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced.     

Acetylcholine-induced coronary vasoconstriction and vasodilation in tranquilized baboons

To determine the effects of acetylcholine on the coronary bed in the baboon and whether the effects preceded or followed the action of acetylcholine on ventricular function, eight adult baboons (Papio anubis) were instrumented to measure left ventricular (LV) and mean arterial pressures, LV dP/dt, regional myocardial function, and coronary blood flow. Acetylcholine was injected locally through a catheter positioned in the coronary artery ostium using fluoroscopic guidance in intact sedated baboons. With heart rate held constant, intracoronary acetylcholine (0.5 micrograms/kg) reduced coronary blood flow by 82 +/- 4% from a baseline value of 34 +/- 4 ml/min without a significant change in mean arterial pressure and with a reduction in LV dP/dt of only 12 +/- 3%. The decrease in coronary blood flow occurred before either LV dP/dt or regional myocardial function fell in the region of the heart receiving acetylcholine. After the intense coronary constriction, a later phase characterized by dilation was observed. The changes in coronary blood flow with acetylcholine were unaffected by combined alpha- and beta-adrenoceptor blockades but were abolished by muscarinic blockade. Low doses of acetylcholine elicited only coronary vasodilation. All doses of acetylcholine, administered directly into the iliac artery, also elicited only iliac vasodilation. Intracoronary acetylcholine in conscious dogs also induced only coronary vasodilation, whereas in conscious calves at higher doses, initial vasoconstrictor responses were observed, which also preceded reductions in regional myocardial function. These results suggest that the controversy surrounding the effects of acetylcholine can be reconciled on the basis of species, vascular bed studied, and dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function.

The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment.     

Left atrial and left ventricular diastolic function during acute myocardial ischaemia

Objective—To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia.

Design—Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery.

Patients—20 patients with isolated disease of the left anterior descending artery and normal left ventricular function.

Results—The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by −37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by −11%).

Conclusions—Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.

     

Effects of ischemia on myocardial function during rapid left ventricular pacing

INTRODUCTION: Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. METHODS: In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. RESULTS: Significant differences (p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1+/-1.6 vs. 10.8+/-1.6%), and QRS duration (77.3+/-4.1 vs. 85.7+/-3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences (p < 0.05) were seen for myocardial contractility dP/dt(max) (1277+/-197 vs. 1158+/-156 mm Hg/s), segmental shortening (10.3+/-1.9 vs. 8.1+/-1.7%), left ventricular end-systolic pressure (76.9+/-7.5 vs. 69.6+/-7.9 mm Hg), and QRS duration, and for myocardial contractility dP/dt(max) (1033+/-209 vs. 917+/-207 mm Hg/s) and left ventricular end-systolic pressure (69.2+/-13.5 vs. 62.2+/-15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. CONCLUSIONS: During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.     

The efficacy of intermittent coronary sinus occlusion in the absence of coronary artery collaterals

The purpose of this study was to evaluate the efficacy of time-controlled intermittent coronary sinus occlusion (ICSO) in preserving regional and global mechanical function during acute ischemia in an animal preparation without significant arterial collateral vessels. Seventeen (eight control, nine ICSO) swine heart preparations undergoing extracorporeal coronary perfusion in situ were subjected to ligation of the left anterior descending coronary artery (LAD) distal to the first major diagonal branch. Data were obtained before and immediately after coronary artery ligation in both animal groups. ICSO, 15 sec of occlusion alternating with 5 sec of release, was then begun in the treatment group. Additional data were obtained in both control and treatment groups at 15 min intervals for 1 hr starting immediately after coronary artery ligation. Global left ventricular function was assessed by shifts in left ventricular end-diastolic pressure and left ventricular dP/dt with left ventricular systolic pressure maintained at about 100 mm Hg. Regional mechanical function was evaluated with transmurally placed ultrasonic crystals. Pressure was also measured directly in the coronary sinus and LAD distal to the ligature. Regional myocardial blood flow was measured in the ischemic bed using 9 micron diameter radiolabeled microspheres injected before, immediately after, and 60 min after coronary artery ligation in both treated and control animals. LAD mean pressure measured distal to the ligation (less than 16 mm Hg) and ischemic bed myocardial blood flow (less than 0.01 ml/g/min) confirmed the absence of significant arterial-arterial collaterals in this preparation. Mean coronary sinus pressure increased significantly (p less than .001) in treated animals during ICSO (e.g., 11.2 +/- 1.6 to 66.2 +/- 10.0 mm Hg at 15 min after coronary ligation). Mean LAD pressure distal to the coronary ligature also increased during ICSO (14.2 +/- 1.2 to 26.8 +/- 1.6 mm Hg), with a similar but delayed rate of pressure rise. No significant differences in left ventricular end-diastolic pressure or left ventricular dP/dt were noted between control or treated animals after coronary ligation. Ischemic bed systolic wall thickening, present before coronary ligation, was not present after occlusion and was not improved during intermittent coronary sinus occlusion in the treatment group. We conclude that in an animal preparation without significant collateral circulation, intermittent coronary sinus occlusion is incapable of restoring regional or global left ventricular mechanical function during conditions of acute ischemia.     

Proposed mechanism for depression of maximal rate of left ventricular pressure fall (peak negative dP/dt) during regional myocardial ischemia

To investigate the mechanism of the depression of left ventricular (LV) peak negative dP/dt during acute regional ischemia, studies were performed in seven open-chest anesthetized dogs. Regional LV wall thickness was measured with ultrasonic crystals in both an ischemic and a normally perfused segment. Ischemia was produced by complete occlusion of the left anterior descending coronary artery for 30 seconds. Within 10 seconds of ischemia, premature thinning of the ischemic wall developed, which preceded thinning of the normal LV wall by 100 +/- 20 msec. Premature thinning of the ischemic segment was associated with 29% reduction of peak negative dP/dt, a 29% prolongation of LV isovolumic relaxation time, and a 15% reduction of the LV systolic ejection period. We offer the following explanation for the depression of LV peak negative dP/dt. 1. Peak negative dP/dt is depressed as a result of a prolongation of the isovolumic relaxation time. 2. The isovolumic relaxation time is prolonged as a result of shortening of the systolic ejection period. 3. Shortening of the systolic ejection period is mediated by an early fall of LV systolic pressure caused by inability of the LV to sustain systolic pressure. 4. Inability of the LV to sustain systolic pressure is caused by premature thinning of the ischemic region during late systole.     

Ischaemia induced development of functional coronary collateral circulation in ponies

The response of coronary collaterals in nine ponies subjected to repeated reversible occlusions (2 min duration, 30 min interval) of the left anterior descending coronary artery was studied at rest. Each pony was instrumented with a Doppler flowmeter and hydraulic cuff occluder around the left anterior descending coronary artery, left ventricular subendocardial sonomicrometers, and a left ventricular micromanometer. Initial occlusions increased end diastolic myocardial segment length by 3% and decreased segment systolic shortening, stroke work, and velocity of shortening by 103%, 95%, and 79% respectively in the left ventricular apex. Left ventricular systolic and end diastolic pressure, peak positive dP/dt, and heart rate were not significantly changed by occlusion. After 421(70) (mean(SEM)) occlusions no sustained alterations in myocardial segment function occurred in response to occlusion. Thus the presence of a subendocardial plexus did not protect against a severe loss of myocardial segment function when the ponies were initially subjected to occlusions of the left anterior descending coronary artery. However, repeated reversible occlusions enhanced coronary collateral blood flow such that it was adequate to maintain left ventricular function in the absence of left anterior descending coronary artery flow. It is concluded that the pony is highly suitable for use in studies of coronary collateral circulation because of its coronary anatomical similarity to man and its capacity to develop functional collateralisation.     

Neurally mediated depressor hemodynamic response induced by intracoronary catheter balloon inflation in pigs

OBJECTIVES: To assess whether intracoronary catheter balloon inflation triggers a neurally mediated hemodynamic response that interacts with the ischemia-induced myocardial dysfunction. METHODS: Forty-eight chloralose anesthetized pigs underwent a 60 s intraluminal catheter balloon inflation of the proximal left anterior descending (LAD) coronary artery before and after one of these treatments: disruption of LAD pericoronary nerves with phenol (n=6), bilateral stellectomy (n=8), bilateral cervical vagotomy (n=6), atropine (n=5), and ganglionic blockade with hexamethonium (n=10). In 13 other pigs, we assessed the reproducibility of two balloon inflations spaced 15 min (n=6) or 60 min (n=7). The ECG, left ventricular (LV) pressure, and LV dP/dt were recorded during each intervention. Right ventricular (RV) pressure, RV dP/dt, and aortic blood flow were also measured in a subset of pigs. RESULTS: Balloon inflation induced an early (10 s) and reproducible (ANOVA, P<0.001) drop in systolic pressure and peak dP/dt; a decrease in aortic blood flow; a rise in end-diastolic pressure; and elevation of the ST segment. Pericoronary denervation, stellectomy and ganglionic blockade attenuated (P<0.001) the drop in LV parameters during coronary inflation, but atropine and vagotomy did not. CONCLUSIONS: A depressor hemodynamic response subserved by pericoronary nerves worsens the LV dysfunction induced by brief coronary catheter balloon inflation in anesthetized pigs. Cholinergic fibers do not appear to play a major role.     

Changes in hemodynamics and bradykinin concentration in coronary sinus blood in experimental coronary artery occlusion.

The following parameters were studied before and after acute occlusion of the anterior descending branch of the left coronary artery in 17 dogs: bradykinin (BK) in the coronary sinus blood, heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular max dp/dt (LV max dp/dt), and an index of myocardial contractility (LV max dp/dt/IP). BK levels increased, reaching a maximum of 30 +/- 13 ng/ml 2 min after coronary ligation, accompanied by a significant elevation of LVEDP, and lowering of the myocardial contractility index. HR and LV max dp/dt showed no significant changes. A positive correlation obtained between the level of BK and LVEDP, as well as a negative correlation between the level of BK and of both LVSP and myocardial contractility index. Pretreatment with aprotinine (Trasylol), an inhibitor of kinin forming enzyme, prevented the increase in both BK and LVEDP after coronary artery ligation and caused an elevation of myocardial contractility index. These results suggest that BK formed within ischemic myocardium exerts a negative inotropic action on the heart.     

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)     

Evaluation of parameters for the assessment of regional myocardial contractile function during asynchronous left ventricular contraction

Summary The primary purpose of this study was to evaluate parameters used for the measurement of regional myocardial contractile function in the setting of left ventricular (LV) asynchrony. Secondarily, we tested whether the peak negative value of left ventricular dP/dt (-dP/dt) can be used to estimate global LV end-systole during asynchrony. In seven anesthetized (Isoflurane) swine the left anterior descending coronary artery was cannulated and perfused at constant blood flow rates. To produce LV asynchrony, dobutamine (D) was infused into the perfusion system. This was repcated later during coronary hypoperfusion (HYPO) sufficient to produce regional contractile dysfunction. The amount of LV wall thickening during systole (% WT, sonomicrometry) was calculated using either - dP/dt or the closure of the aortic valve (AO, electromagnctic flow probc) for estimating the timing of global LV end-systole. % WT was compared to other paramcters which are not dependent upon the timing of global LV end-systole, including the amplitude of the first harmonic of the Fourier transform (AMP) and regional myocardial work (WI) estimated from the left ventricular pressure-wall thickness relationship. A close correlation between global LV end-systole defined by the AO or - dP/dt existed during control. D or HYPO. During HYPO+D no such relationship was found (r=.22, NS), and % WT calculated using - dP/dt as an estimate of end-systole was underestimated when comparcd to % WT calculated by use of the AO to estimate end-systole (2.9±6.8% vs 6.3±6.6%, p<.05). % WT, AMP, and WI showed similar results during control, D and HYPO. However, D during HYPO increased the AMP from .59±.23 mm to .76±.32 mm and WI from 67±20 mm Hg*mm to 95±24 mm Hg*mm (p<.05), respectively. This increase in regional myocardial function, however, was not detected by % WT (10.5±6.4% vs 6.3±6.6%). Thus, during left ventricular asynchrony, the measurement of LV-dP/dt to estimate the timing of global LV end-systole is inappropriate and can lcad to inaccuracies in the measurement of regional contractile function. Parameters such as AMP or WI are advantageous since global LV end-systole docs not need to be accurately defined.Supported in part by the American Heart Association California Affiliate grant-in-aid #86-S105, and by the German Research Foundation (He 1320/3-2). Dr. Guth is the recipient of a Research Fellowship from the Alexander von Humboldt-Stiftung, Jean-Paul-Straße 12, D-5300 Bonn 2