THE LOSS OF PACING-INDUCED PRECONDITIONING IN ATHEROSCLEROTIC RABBITS- ROLE OF HYPERCHOLESTEROLEMIA

A brief rapid pacing has been shown to protect rabbit heart against gl obal myocardial ischaemia induced by subsequent longer pacing. We stud ied whether pacing-induced preconditioning was reproducible in experim ental hypercholesterolaemia. In conscious rabbits with an implanted ri ght ventricular electrode and left ventricular polyethylene catheters, pacing of 500 bpm over 20 min induced an intracavitary ST-segment ele vation of 3.2 +/- 0.41 mV, shortened ventricular effective refractory period and increased left ventricular end-diastolic pressure from prep acing 105 +/- 3.9 ms and 4.0 +/- 0.93 mmHg to post-pacing 62 +/- 6.4 m s and 27.9 +/- 7.2 mmHg, respectively. A 10-min preconditioning pacing followed by a 5-min interval markedly attenuated these test pacing-in duced ischaemic changes. Rabbits were fed a cholesterol-enriched diet over 4, 8 and 12 weeks, responded to a 5- or 10-min pacing with ischae mic changes of the same degree as did controls to a 10- or 20-min paci ng, respectively. A 4-week diet elevated total serum cholesterol from 1.7 +/- 0.4 to 24.1 +/- 2.9 mmol/l without apparent atherosclerotic le sions in the thoracic aorta assessed by Oil-Red O staining and planime try, but it abolished protection induced by a 5 min preconditioning pa cing. A 12-week diet increased serum cholesterol and lesion surface ar ea to 26.9 +/- 3.2 mmol/l and 89.6 +/- 6.4%, respectively, and continu ed to block preconditioning, When these animals were refed normal chow over additional 6 weeks, serum cholesterol level dropped to 2.6 +/- 0 .80 mmol/l with no change in atherosclerotic lesions, the precondition ing effect, however, recovered. We conclude that hypercholesterolaemia blocks preconditioning irrespective of the development of atheroscler osis. (C) 1995 Academic Press Limited