Acute decrease in left ventricular diastolic chamber distensibility during simulated angina in isolated hearts

Abstract

It is not clear that factors contribute to the prompt and reversible decrease in left ventricular diastolic chamber distensibility during angina pectoris that is induced by an increase in myocardial energy demand due to exercise or pacing tachycardia. To simulate the demand ischemia that occurs clinically during pacing-induced angina, we used isolated, blood-perfused rabbit hearts with restricted coronary flow and increased myocardial energy demand. A constant left ventricular balloon volume model was used to measure left ventricular diastolic chamber distensibility during 6 minutes of low-flow global ischemia, induced by a reduction in coronary perfusion pressure from 100 to 20 mm Hg. To investigate the influence of different levels of myocardial energy demand, the effects of two different heart rates were studied during low-flow global ischemia; pacing tachycardia (6.4 ± 0.2 Hz, n = 7) was compared with the rabbit's baseline heart rate of 4 Hz (n = 7). Low-flow ischemia caused a marked decrease in contractile function relative to the baseline preischemic state. In the pacing-tachycardia group, myocardial energy demand, as estimated by the rate x systolic pressure product, was significantly greater than in the constant heart-rate group. When tachycardia was imposed during low-flow global ischemia, there was a transient and reversible increase in isovolumic left ventricular end-diastolic pressure from 14 ± 1 to 25 ± 4 mm Hg (measured during long diastoles obtained with transient cessation of pacing) in the pacing-tachycardia group, but there was no increase in left ventricular end-diastolic pressure during low flow ischemia in the constant heart-rate group with lower energy demand (p < 0.01). The time constant of left ventricular relaxation also markedly increased in low-flow ischemia combined with pacing tachycardia. Glycolytic flux (as estimated by coronary venous-arterial lactate concentration difference) increased during low-flow ischemia at the baseline heart rate of 4 Hz but did not increase further during the elevated energy demand of pacing tachycardia. We conclude that in isolated, blood-perfused hearts, global myocardial ischemia due to a reduction in coronary flow alone is not associated with a decrease in diastolic chamber distensibility. However, when a pacing-induced increase in myocardial energy demand is superimposed on the ischemic myocardium and exceeds its capacity to generate high-energy phosphates, a rapid and reversible decrease in left ventricular diastolic chamber distensibility develops similar to that which occurs in response to pacing-induced angina in humans. This finding in isolated, blood-perfused hearts with global ischemia supports the hypothesis that the increase in left ventricular diastolic pressure that occurs during angina in humans is related to the effects of demand ischemia on myocardial relaxation per se and does not require dyssynchronous contraction of ischemic and nonischemic segments, nor does it depend on pericardial or right ventricular factors.