CARBOHYDRATES AND PURINES IN UNDERPERFUSED HEARTS, PROTECTED BY ISCHEMIC PRECONDITIONING

Few results, and those controversial, have been published on ischemic preconditioning followed by low-now ischemia. The aim of this study wa s to assess whether ischemic preconditioning: (1) confers protection a gainst severe underperfusion; and (2) is mediated by mobilization of p roglycogen, resulting in increased anaerobic glycolysis and reduced my ocardial injury. Isolated rat hearts were retrogradely perfused and su bjected to either 25 min low-now ischemia (0.6 ml/min) followed by 30 min reperfusion (IC; n = 5), or the same protocol preceded by two cycl es of 5 min no-now ischemia and 5 min reperfusion (PC: n = 7). Additio nally, hearts (n = 52) were freeze-clamped at different time points th roughout the protocol. Preconditioning improved functional recovery (d eveloped force x heart rate in PC hearts: 54 v 21% in IC hearts: P<0.0 1) and reduced ischemic damage (cumulative release of creatine kinase during reperfusion: 93 v 215 U/g dry weight; P<0.05). During ischemia and reperfusion, release of adenosine and the sum of purines was small er in PC hearts (P<0.05), while lactate release was similar in the two groups. PC reduced both macroglycogen and proglycogen by c. 60% (P<0. 01) resulting in constant glycogen levels during low-now ischemia. In contrast, in IC hearts, both fractions decreased by c. 60% during unde rperfusion (P<0.01). These results demonstrate that: (1) ischemic prec onditioning reduces injury due to severe flow reduction; and (2) preco nditioning reduced glycogenolysis without affecting anaerobic glycolys is, suggesting increased glucose uptake. (C) 1998 Academic Press Limit ed.