Carbohydrates and purines in underperfused hearts, protected by ischemic preconditioning.
Few results, and those controversial, have been published on ischemic preconditioning followed by low-flow ischemia. The aim of this study was to assess whether ischemic preconditioning: (1) confers protection against severe underperfusion; and (2) is mediated by mobilization of proglycogen, resulting in increased anaerobic glycolysis and reduced myocardial injury. Isolated rat hearts were retrogradely perfused and subjected to either 25 min low-flow ischemia (0.6 ml/min) followed by 30 min reperfusion (IC; n=5), or the same protocol preceded by two cycles of 5 min no-flow ischemia and 5 min reperfusion (PC; n=7). Additionally, hearts (n=52) were freeze-clamped at different time points throughout the protocol. Preconditioning improved functional recovery (developed force X heart rate in PC hearts: 54 v 21% in IC hearts; P<0.01) and reduced ischemic damage (cumulative release of creatine kinase during reperfusion: 93 v 215 micro/g dry weight; P<0.05). During ischemia and reperfusion, release of adenosine and the sum of purines was smaller 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-flow ischemia. In contrast, in IC hearts, both fractions decreased by c. 60% during underperfusion (P<0.01). These results demonstrate that: (1) ischemic preconditioning reduces injury due to severe flow reduction; and (2) preconditioning reduced glycogenolysis without affecting anaerobic glycolysis, suggesting increased glucose uptake.
de Jonge
R
R
Cardiochemical Laboratory, ThoraxCenter, Erasmus University Rotterdam, The Netherlands.
Bradamante
S
S
Speleman
L
L
Willem de Jong
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050260:Carbohydrate Metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D011687:Purines; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose