DIACYLGLYCEROL-INDUCED PROTECTION AGAINST INJURY DURING ISCHEMIA AND REPERFUSION IN THE RAT-HEART - COMPARATIVE-STUDIES WITH ISCHEMIC PRECONDITIONING

The role of protein kinase C (PKC) activation in ischemic precondition ing remains controversial. Since diacylglycerol is the endogenous acti vator of PKC and as such might be expected cardioprotective, we have i nvestigated whether: (i) the diacylglycerol analog 1,2-dioctanoyl-sn-g lycerol (DOG) can protect against injury during ischemia and reperfusi on; (ii) any effect is mediated via PKC activation; and (iii) the outc ome is influenced by the time of administration. Isolated rat hearts w ere perfused with buffer at 37 degrees C and paced at 400 bpm. In Stud y 1, hearts (n = 6/group) were subjected to one of the following: (1) 36 min aerobic perfusion (controls); (2) 20 min aerobic perfusion plus ischemic preconditioning (3 min ischemia/3 min reperfusion+5 min isch emia/5 min reperfusion); (3) aerobic perfusion with buffer containing DOG (10 mu M) given as a substitute for ischemic preconditioning; (4) aerobic perfusion with DOG (10 mu M) during the last 2 min of aerobic perfusion. All hearts then were subjected to 35 min of global ischemia and 40 min reperfusion. A further group (5) were perfused with DOG (1 0 mu M) for the first 2 min of reperfusion. Ischemic preconditioning i mproved postischemic recovery of LVDP from 24+/-3% in controls to 71 /- 2% (P<0.05). Recovery of LVDP also was enhanced by DOG when given j ust before ischemia (54+/-4%), however, DOG had no effect on the recov ery of LVDP when used as a substitute for ischemic preconditioning (22 +/-5%) or when given during reperfusion (29+/-6%). In Study 2, the fir st four groups of study were repeated (n=4-5/group) without imposing t he periods of ischemia and reperfusion, instead hearts were taken for the measurement of PKC activity (pmol/min/mg protein+/-SEM). PI(C acti vity after 36 min in groups (1), (2), (3) and (4) was: 332+/-102, 299/-63, 521+/-144, and 340+/-113 and the membrane:cytosolic PKC activity ratio was: 5.6+/-1.5, 5.31+/-1.8, 6.6+/-2.7, and 3.9+/-2.1 (P=NS in e ach instance). In conclusion DOG is cardioprotective but under the con ditions of the present study is less cardioprotective than ischemic pr econditioning, furthermore the protection does not appear to necessita te PKC activation prior to ischemia. (C) 1998 Elsevier Science Ireland Ltd.