CARDIOPROTECTIVE EFFECTS OF ISCHEMIC PRECONDITIONING CAN BE RECAPTURED AFTER THEY ARE LOST

Objectives. We sought to determine whether the cardioprotective effects of ischemic preconditioning can be reinstated once they are lost in a rat model of coronary occlusion. Background. We have shown in a previous study that the cardioprotective effects of preconditioning are lost if there is a time lag (greater than or equal to 1 h) between the preconditioning and sustained coronary occlusion events in the rat. However, whether the beneficial effects of preconditioning can be regained once they are lost in this model is unknown. Methods. Twenty-eight rats were randomized to one of four groups. Group 1 (control group) underwent 90 min of coronary occlusion without preconditioning. Group 2 had preconditioning (three cycles of 3 min of coronary occlusion and 5 min of reperfusion) that was immediately followed by 90 min of coronary occlusion. In group 3, 90 min of occlusion was delayed by 1 h after preconditioning. In group 4, preconditioning was repeated Ih after a first preconditioning sequence, followed by 90 min of occlusion. After 4 h of reperfusion, the area at risk was delineated by intravenous injection of blue dye during a brief coronary occlusion, and the area of necrosis was determined by the triphenyltetrazolium chloride technique. Results. Myocardial infarct size, expressed as a percent of the anatomic area at risk in groups 1 and 3 averaged 44.1 +/- 6.9% (mean +/- SEM) and 49.9 +/- 6.9%, respectively. In contrast. groups 2 and 4 (12.1 +/- 3.2% and 10.1 +/- 2.6%, respectively) had a significantly smaller infarct size (p < 0.01 vs. groups 1 and 3). The incidence of ventricular tachycardia during the 90 min of coronary occlusion in both groups 2 and 4 (14.3%, p < 0.005 and 28.6%, p < 0.05, respectively) was significantly lower than in groups 1 and 3 (100% in both groups). Conclusions. Repeat preconditioning at 1 h was capable of recapturing the cardioprotective effects of preconditioning on both infarct size and ventricular arrhythmia.