Improved myocardial preservation with short hyperthermia prior to cold cardioplegic ischemia in immature rabbit hearts

Objective: Recent observations have been shown that the induction and accum ulation of heat shock proteins (HSPs) by short exposure to nonlethal whole- body hyperthermia with normothermic recovery are closely associated with tr ansient resistance to subsequent ischemia-reperfusion challanges. Here, thi s study was performed to investigate whether a shortly heat shock pretreatm ent affects the left ventricular (LV) function after cold cardioplegic isch emia in reperfused neonatal rabbit hearts. Methods: Hearts from neonatal Ne w Zealand White rabbits were isolated perfused (working heart preparation) and exposed to 2 h of cold cardioplegic ischemia followed by reperfusion fo r 60 min. To induce the heat shock response neonatal rabbits (n = 5, HT-gro up) were subjected to whole-body hyperthermia at 42.0-42.5 degrees C for 15 min, followed by a normothermic recovery period of 60 min, before harvesti ng and the onset of global hypothermic cardioplegic arrest. Another set of hearts (n = 5, control group) without a heat treatment underwent a similar perfusion and ischemia protocol served as control. The postischemic recover y was assessed by measuring several parameters of LV function. LV biopsies from all control and heat treated animals were taken before ischemia and at the end of reperfusion to examine myocardial HSP levels by Western blot an alysis. Results: At 60 min of reperfusion the MT-group showed significant b etter recovery of ventricular function such as LV developed pressure (DP) ( 74.6 +/- 10 vs. 52.1 +/- 8.5%, P < 0.05), LV positive dP/dt (910 +/- 170 vs . 530 +/- 58 mmHg/s, P < 0.01) and LV end-diastolic pressure (LVEDP) (8 +/- 2 vs. 18.4 +/- 5 mmHg, P < 0.05) than control. Myocardial oxygen consumpti on (MVO2) was significantly higher in the HT-group compared with control (0 .054 +/- 0.006 vs. 0.041 +/- 0.002 ml/g per min, P < 0.05). Significant pos treperfusion lower level in lactate production was observed in the HT-group (0.83 +/- 0.11 vs. 1.67 +/- 0.8 mmol/l, P < 0.05). Also, the recovery of h emodynamic parameters such as aortic how, coronary flow and cardiac output was significantly superior (P < 0.05) in the MT-group. Furthermore, high ex pression of MSP72(+)/73(+) were detected in the myocardial tissue samples o f heat-treated rabbits by immunoblotting, appearing even at 60 min of normo thermic recovery after heat stress. Conclusions: These data in the immature rabbit heart indicate that previous shortly heat treatment with high level expression of heat shock proteins (HSP72(+)/73(+)) before hypothermic card ioplegic ischemia provides transient tolerance against myocardial injury an d could be an improvement for the postischemic functional recovery of neona tal hearts. (C) 2000 Elsevier Science B.V. All rights reserved.