IMPAIRED CARDIOPLEGIC DELIVERY AND THE LOSS OF CARDIOPROTECTION - A ROLE FOR PRECONDITIONING

We have previously shown that, while ischemic preconditioning and card ioplegia afford similar protection against injury during ischemia and reperfusion, this protection is not additive. However, it is not known whether the same applies when the delivery of cardioplegia is subopti mal, such as may occur in the case of a coronary stenosis. To investig ate the protective effect of cardioplegia v preconditioning when the d elivery of cardioplegia is impaired, isolated rat hearts were subjecte d to 40 min of global ischemia followed by 40 min of reperfusion. Seve n groups of hearts (1 g wet wt) were studied (n=8/group): Group 1: con trols with unprotected ischemia (no intervention); Group 2: in which o nly 0.2 ml of the St Thomas' cardioplegic solution was administered (2 min) prior to ischemia; group 3: in which the volume of cardioplegic solution was increased to 0.5 mi; Group 4: received 1.0 ml of cardiopl egia; Group 5: received 2.0 mi of cardioplegia; Group 6: were subjecte d to ischemic preconditioning (3 min ischemia, 3 min reperfusion, 5 mi n ischemia, 5 min reperfusion) prior to ischemia; and Group 7: in whic h ischemic preconditioning and cardioplegia (1.0 mi) were used in comb ination. The mean postischemic recovery of left ventricular developed pressure (LVDP), expressed as a percentage of its pre-ischemic value, was 33 +/- 3% in the control group; this was significantly improved (P <0.05) in hearts receiving 2.0 mi of cardioplegia (59 +/- 5%), whereas volumes of 0.2, 0.5 or 1.0 mi of cardioplegia afforded no significant protection (recoveries of LVDP were 32 +/- 6%, 37 +/- 5% and 37 +/- 5 %, respectively). Preconditioning alone and the combination of precond itioning plus 1.0 ml of cardioplegia afforded similar protection (57 /- 3% and 5.8 +/- 3%; P<0.05 v controls). At the end of reperfusion, l eft ventricular end-diastolic pressure (LVEDP) was substantially incre ased in control hearts (57 +/- 3 mmHg); it was decreased in the group receiving 2.0 mi of cardioplegic solution (40 +/- 5 mmHg; P<0.05 v con trol group), but not in the groups receiving 0.2, 0.5 or 1.0 mi of car dioplegic solution (59 +/- 4, 55 +/- 3 and 54 +/- 4 mmHg, respectively ). Again, preconditioning alone or preconditioning plus 1.0 mi of card ioplegia afforded similar good protection (39 +/- 1 mmHg and 37 +/- 2 mmHg, respectively). A similar pattern was observed for the post-ische mic recovery of coronary now. Under conditions where the delivery of c ardioplegia is impaired (<2.0 ml/g myocardium) preconditioning, alone or preconditioning in combination with cardioplegia is more protective that cardioplegia alone, These results may be of clinical interest be cause most patients undergoing surgery for ischemic heart disease suff er from severe coronary artery lesions that may prevent the delivery o f sufficient cardioplegic solution to ensure maximum protection. (C) 1 997 Academic Press Limited.