DICHOTOMY OF ISCHEMIC PRECONDITIONING - IMPROVED POSTISCHEMIC CONTRACTILE FUNCTION DESPITE INTENSIFICATION OF ISCHEMIC CONTRACTURE

Background Acceleration of ischemic contracture is conventionally acce pted as a predictor of poor postischemic function. Hence, protective i nterventions such as cardioplegia delay ischemic contracture and impro ve postischemic contractile recovery. We compared the effect of ischem ic preconditioning and cardioplegia (alone and in combination) on isch emic contracture and postischemic contractile recovery. Methods and Re sults Isolated rat hearts were aerobically perfused with blood for 20 minutes before being subjected to zero-flow normothermic global ischem ia for 35 minutes and reperfusion for 40 minutes. Hearts were perfused at a constant pressure of 60 mm Hg and were paced at 360 beats per mi nute. Left ventricular developed pressure and ischemic contracture wer e assessed with an intraventricular balloon. Four groups (n=8 hearts p er group) were studied: control hearts with 35 minutes of unprotected ischemia, hearts preconditioned with one cycle of 3 minutes of ischemi a plus 3 minutes of reperfusion before 35 minutes of ischemia, hearts subjected to cardioplegia with St Thomas' solution infused for 1 minut e before 35 minutes of ischemia, and hearts subjected to preconditioni ng plus cardioplegia before 35 minutes of ischemia. After 40 minutes o f reperfusion, each intervention produced a similar improvement in pos tischemic left ventricular developed pressure (expressed as a percenta ge of its preischemic value: preconditioning, 44+/-2%; cardioplegia, 5 3+/-3%; preconditioning plus cardioplegia, 54+/-4%; and control, 26+/- 6%, P<.05). However, preconditioning accelerated whereas cardioplegia delayed ischemic contracture; preconditioning plus cardioplegia gave a n intermediate result. Thus, times to 75% contracture were as follows: control, 14.3+/-0.4 minutes; preconditioning, 6.2+/-0.3 minutes; card ioplegia, 23.9+/-0.8 minutes; and preconditioning plus cardioplegia, 1 5.4+/-12.4 minutes (P<.05 preconditioning and cardioplegia versus cont rol). In additional experiments, using blood- and crystalloid-perfused hearts, we describe the relationship between the number of preconditi oning cycles and ischemic contracture. Conclusions Although preconditi oning accelerates, cardioplegia delays, and preconditioning plus cardi oplegia has little effect on ischemic contracture, each affords simila r protection of postischemic contractile function. These results quest ion the utility of ischemic contracture as a predictor of the protecti ve efficacy of anti-ischemic interventions. They also suggest that pre conditioning and cardioplegia may act through very different mechanism s.