Normothermic transfer times up to 3 min will not precondition the isolatedrat heart

Isolated, perfused heart preparations suffer an inevitable peri-operative d elay (POD) before retrograde perfusion restores coronary flow. By varying t his ischaemic period we investigated the threshold of POD-induced inadverte nt preconditioning (PC) in the rat heart. Hearts subjected to POD at 37 deg rees C increasing from 1, 2, 3, 5, 10 up to 15 min prior to 20 min retrogra de perfusion were further subjected to 30 min global, normothermic ischaemi a and 30 min reperfusion (index I/R), The functional recovery was 32 +/- 4. 1% in hearts subject to 1 min POD. lifter 3 min POD functional recovery sta rted to improve and peaked at 10 min POD (78 +/- 7.1%. P<0.001). At 4 degre es C functional recovery started to improve after 5 min POD and peaked at 1 0 min POD. To demonstrate that the POD-mediated protection was true PC, two conventional models of PC were established. In both models, hearts were re trogradely pel fused within 1 min POD prior to a standard PC protocol (one episode of 10 min ischaemia, or four episodes of 5 min ischaemia). In the c onventional PC models protection against the index I/R was abolished using 100 mu M 5-hydroxydecanoate (5-HD), the mitrochondrial K-ATP channel inhibi tor. Likewise. 10 min POD-mediated recovery at 37 degrees C (70 +/- 3.2%) w as reversed by 100 mu M 5-HD perfusion (36 +/- 5.9%; NS vs 2 min POD), We c onclude: iii the threshold for PC is greater than 3 min at 37 degrees C and greater than 5 min at 4 degrees C: (2) blockade of the mitochondrial K-ATP channel abolishes protection in three models of PC in the rat heart, inclu ding prolonged POD. (C) 1999 Academic Press.