Abstract
To clarify conflicting reports concerning the effects of ischemia on left ventricular chamber stiffness, we compared the effects of hypoxia at constant coronary perfusion with those of global ischemia on left ventricular diastolic chamber stiffness using isolated, perfused rabbit hearts in which the left ventricle was contracting isovolumically. Since chamber volume was held constant, increases in left ventricular end diastolic pressure (LVEDP) reflected increases in chamber stiffness. At a control coronary flow rate (30 ml/min), 2 min of hypoxia and pacing tachycardia (4.0 Hz) produced major increases in postpacing LVEDP (10+/-1 to 24+/-3 mm Hg, P < 0.01) and the relaxation time constant, T, (40+/-4 to 224+/-37 ms, P < 0.001), while percent lactate extraction ratio became negative (+ 18+/-2 to -48+/-15%, P < 0.001). Coronary perfusion pressure decreased (72+/-5 to 52+/-3 mm Hg, P < 0.01), and since coronary flow was held constant, the fall in coronary perfusion pressure reflected coronary dilation and a decrease in coronary vascular resistance. Following an average of 71+/-6s reoxygenation and initial heart rate (2.0 Hz), LVEDP and relaxation time constant T returned to control. Hypoxia alone (without pacing tachycardia) produced similar although less marked changes (LVEDP, 10+/-1 to 20+/-3 mm Hg; and T, 32+/-3 to 119+/-22 ms; P < 0.01 for both) and there was a strong correlation between LVEDP and T (r = 0.82, P < 0.001). When a similar degree of coronary vasodilatation was induced with adenosine, no change in LVEDP occurred, indicating that the increase in end diastolic pressure observed during hypoxia was not secondary to vascular engorgement, but due to an acute effect of hypoxia on the diastolic behavior of the ventricular myocardium. In contrast, global ischemia produced by low coronary flow (12-15 ml/min) resulted in a decrease in LVEDP, as well as a marked fall in left ventricular systolic pressure. In 14 global ischemia experiments, pacing tachycardia led to a further decline in left ventricular systolic pressure, and no increase was noted in postpacing LVEDP. Changes in lactate extraction ratio were much smaller in magnitude than with hypoxia and constant coronary perfusion. In two experiments (one at normal coronary flow and one at 15 ml/min), left ventricular systolic pressure did not change markedly from control when tachycardia was superimposed, and postpacing LVEDP showed a marked rise (to > 25 mm Hg), which gradually recovered over 1-2 min at the control heart rate. From these results, we conclude that left ventricular chamber stiffness increases when myocardial O(2) demand exceeds supply. This change is usually masked in ischemic (reduced coronary flow) preparations, perhaps because of reduced turgor of the coronary vascular bed, marked reductions in systolic work (and therefore myocardial O(2) requirements), and local accumulation of hydrogen ion and metabolites following acute severe reduction of coronary flow. The increased chamber stiffness during hypoxia is accompanied by marked slowing of relaxation, with increased diastolic pressure relative to volume persisting throughout diastole.