Objectives: The increased susceptibility to ischemic injury of hypertrophied hearts has long been recognized. The purpose of this study was to investigate the effects of pre-ischemic pharmacological preconditioning (PC) with adenosine A(1) or A(3) receptor activation, on the recovery of the isolated myocardium post cardioplegic ischemia. In addition, we examined the p38 MAPK activation in this process.
Materials and methods: WKY and SHR hearts were subjected to two different modes of treatment. (1) In the perfusion mode- (the first window of PC) isolated rat hearts were perfused for 10 min with Krebs Henseleit solution and then A(1) receptor agonist (CCPA) or A(3) receptor agonist (Cl-IB-MECA), 10 nM for 20 min, followed by 30 min of warm cardioplegic ischemia and 30 min of reperfusion. (2) In the injection mode (the second window of PC) 100 microg/kg CCPA or Cl-IB-MECA, were administered 24 h before the experiment. Isolated hearts were perfused for 30 min with KH and then subjected to the same protocol as described above.
Results: Recovery of hemodynamic parameters was always better in the normal vs. hypertrophied hearts. CCPA improved recovery of left ventricular developed pressure, coronary flow and ATP levels of the hearts (normal and hypertrophied) in both modes of treatment. Cl-IB-MECA was partially beneficial especially in the injected mode. Increased phosphorylation of p38 MAPK relative to baseline, in both early (perfused) and late (injected) modes of treatment especially in the WKY hearts, is demonstrated.
Conclusion: CCPA in both modes of treatment and Cl-IB-MECA, especially in the injected mode, were beneficial in protecting the normal and hypertrophied perfused isolated rat heart subjected to normothermic cardioplegic ischemia. This protection was partially related to the increased phosphorylation of p38 MAPK.