Increased resistance to ischaemic injury in the isolated perfused atherosclerotic heart of the cholesterol-fed rabbit.

Abstract

In isolated, Langendorff-perfused hearts in the early stages of atherosclerosis from rabbits exposed to hypercholesterolaemia induced by 2% cholesterol feeding for 6 weeks (n = 23), and age-matched normal controls fed standard chow (n = 12), we studied baseline cardiac haemodynamics and the susceptibility of these hearts to 30 min global, normothermic ischaemia and 90 min reperfusion. Spontaneously beating hearts were perfused with oxygenated Krebs buffer (pH 7.4) at constant pressure, and were enclosed in a thermostated water jacket at 37 degrees C. Isovolumetric left ventricular (LV) pressure was measured by means of a balloon placed in the LV cavity. An electromagnetic flow probe placed around the perfusion cannula determined coronary flow. At the end of an initial 30 min stabilisation period, several baseline cardiodynamic variables were measured, just before subjecting the hearts to 30 min ischaemia. Recovery of mechanical function and lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities in the coronary effluent were recorded throughout 90 min reperfusion. Baseline spontaneous heart rate, LV developed pressure (LVDP), coronary flow and pressure-rate index (PRI) were all significantly lower in hearts from cholesterol-fed rabbits (CFR) than in age-matched controls (P < 0.01). Although large differences in several baseline haemodynamic parameters in hearts from CFR and controls were evident before ischaemia, no statistically significant differences were discernible in these parameters between the two groups from 60 min reperfusion onwards (p = NS). Furthermore, CPK and, to a lesser extent, LDH release during reperfusion was attenuated in hearts from CFR compared to controls. Hearts from CFR exhibited markedly improved recovery upon reperfusion compared to age-matched controls, strongly suggesting increased myocardial resistance to ischaemic injury.