INCREASED RESISTANCE TO ISCHEMIC-INJURY IN THE ISOLATED-PERFUSED ATHEROSCLEROTIC HEART OF THE CHOLESTEROL-FED RABBIT

Objective: In isolated, Langendorff-perfused hearts in the early stage s of atherosclerosis from rabbits exposed to hypercholesterolaemia ind uced by 2% cholesterol feeding for 6 weeks (n = 23), and age-matched n ormal 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. Methods: Spontaneousl y beating hearts were perfused with oxygenated Krebs buffer (pH 7.4) a t constant pressure, and were enclosed in a thermostated water jacket at 37 degrees C. Isovolumetric left ventricular (LV) pressure was meas ured by means of a balloon placed in the LV cavity. An electromagnetic flow probe placed around the perfusion cannula determined coronary fl ow. At the end of an initial 30 min stabilisation period, several base line cardiodynamic variables were measured, just before subjecting the hearts to 30 min ischaemia. Recovery of mechanical function and lacta te dehydrogenase (LDH) and creatine phosphokinase (CPK) activities in the coronary effluent were recorded throughout 90 min reperfusion. Res ults: Baseline spontaneous heart rate, LV developed pressure (LVDP), c oronary flow and pressure-rate index (PRI) were all significantly lowe r in hearts from cholesterol-fed rabbits (CFR) than in age-matched con trols (P < 0.01). Although large differences in several baseline haemo dynamic 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 onw ards (p = NS). Furthermore, CPK and, to a lesser extent, LDH release d uring reperfusion was attenuated in hearts from CFR compared to contro ls. Conclusions: Hearts from CFR exhibited markedly improved recovery upon reperfusion compared to age-matched controls, strongly suggesting increased myocardial resistance to ischaemic injury.