DELAYED CARDIAC PROTECTION AGAINST HARMFUL CONSEQUENCES OF STRESS CANBE INDUCED IN EXPERIMENTAL ATHEROSCLEROSIS IN RABBITS

Multiple brief periods of rapid Ventricular pacing confer both short- and long-term protection on the ischaemic heart. The duration of the s hort-term protection does not exceed 2 h, whereas the long-term protec tive effect appears several hours after the inducing insults, with max imal protection 24-48 h later, Up to now, delayed cardiac protection b y preceding ischaemic insults against harmful consequences of stress h as been produced in the normal, healthy animal only. The purpose of th is study was, therefore, to test whether delayed cardiac protection ca n be induced in experimental atherosclerosis in rabbits produced by fe eding cholesterol-rich diet over 2 months, Repeated brief periods of r apid ventricular pacing were used to induce delayed protection of the heart, Moderation of post-pacing right intracavitary ST segment elevat ion and that of the left ventricular end-diastolic pressure (both prod uced by ventricular overpacing: 500 beats/min for 15 min) were found i n normal animals as well as in those fed cholesterol-enriched diet. Th e short-lived protection induced by a single 'preconditioning' pacing was reproducible only in normal animals. As measured by means of radio immunoassay, the protective effect of either short- or long-term prote ction appeared in parallel with an attenuation of ischaemia-induced in crease in cardiac cyclic AMP content, in both normal and atherosclerot ic rabbits, An increase in cardiac cyclic GMP content was characterist ic of the short- but not longterm protection. These results suggest th at the delayed cardiac protection by preceding multiple brief rapid pa cings operates even in experimental atherosclerosis, but the short-ter m protection induced by a single preconditioning stimulus is lost. (C) 1997 Academic Press Limited.