Impaired Cardioplegic Delivery and the Loss of Cardioprotection: a Role for Preconditioning

We have previously shown that, while ischemic preconditioning and cardioplegia 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 suboptimal, such as may occur in the case of a coronary stenosis. To investigate the protective effect of cardioplegiavpreconditioning when the delivery of cardioplegia is impaired, isolated rat hearts were subjected to 40 min of global ischemia followed by 40 min of reperfusion. Seven groups of hearts (1 g wet wt) were studied (n=8/group): Group 1: controls with unprotected ischemia (no intervention); Group 2: in which only 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 ml; Group 4: received 1.0 ml of cardioplegia; Group 5: received 2.0 ml of cardioplegia; Group 6: were subjected to ischemic preconditioning (3 min ischemia, 3 min reperfusion, 5 min ischemia, 5 min reperfusion) prior to ischemia; and Group 7: in which ischemic preconditioning and cardioplegia (1.0 ml) were used in combination. 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 ml of cardioplegia (59±5%), whereas volumes of 0.2, 0.5 or 1.0 ml of cardioplegia afforded no significant protection (recoveries of LVDP were 32±6%, 37±5% and 37±5%, respectively). Preconditioning alone and the combination of preconditioning plus 1.0 ml of cardioplegia afforded similar protection (57±3% and 58±3%;P<0.05vcontrols). At the end of reperfusion, left ventricular end-diastolic pressure (LVEDP) was substantially increased in control hearts (57±3 mmHg); it was decreased in the group receiving 2.0 ml of cardioplegic solution (40±5 mmHg;P<0.05vcontrol group), but not in the groups receiving 0.2, 0.5 or 1.0 ml of cardioplegic solution (59±4, 55±3 and 54±4 mmHg, respectively). Again, preconditioning alone or preconditioning plus 1.0 ml of cardioplegia afforded similar good protection (39±1 mmHg and 37±2 mmHg, respectively). A similar pattern was observed for the post-ischemic recovery of coronary flow. Under conditions where the delivery of cardioplegia 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 because most patients undergoing surgery for ischemic heart disease suffer from severe coronary artery lesions that may prevent the delivery of sufficient cardioplegic solution to ensure maximum protection.