AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 2 718-R725, Copyright © 1997 by American Physiological Society

ARTICLES

Hemorrhage induces acute cardioadaptation to ischemia-reperfusion by an alpha1-adrenoceptor-mediated, protein synthesis-independent mechanism

D. R. Meldrum, J. C. Cleveland Jr, X. Meng, B. C. Sheridan, A. Banerjee and A. H. Harken
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.

Hemorrhage and resuscitation (H-R) has been recognized as an exclusively destructive process that results in multiple organ dysfunction. Although it is well established that endogenous adaptation mechanisms exist, it is unknown whether H-R induces endogenous adaptive/protective mechanisms. Furthermore, alpha1-adrenoceptors and de novo protein synthesis have been variably implicated in myocardial adaptation responses. This study tests the hypothesis that H-R results in myocardial adaptation by a mechanism mediated by alpha1-adrenoceptors and requiring de novo protein synthesis. The aims of the present study were to determine 1) whether H-R stress results in acute cardioadaptation to subsequent global, normothermic ischemia-reperfusion (I-R); 2) whether H-R-induced endogenous adaptation is mediated by alpha1-adrenoceptors; and 3) whether H-R-induced endogenous adaptation requires de novo protein synthesis. Rats were hemorrhaged and resuscitated, sham operated, or neither, with and without prior alpha1-adrenoceptor or protein synthesis inhibition. Hearts were then isolated and subjected to a second insult consisting of global, normothermic I-R (20 min ischemia-40 min reperfusion). The results show that antecedent H-R improved post-I-R left ventricular developed pressure, compliance, coronary flow, and decreased reperfusion creatine kinase loss (P < 0.05, analysis of variance with Bonferroni-Dunn). H-R-induced adaptation was abolished by prior alpha1-adrenoceptor blockade (prazosin, 0.5 mg/kg ip); however, inhibition of de novo protein synthesis (cyclohexamide, 1.0 mg/kg ip) did not affect H-R-induced acute adaptation. This study constitutes the initial demonstration that H-R induces endogenous cardioadaptation, which is mediated by an alpha1-adrenergic signaling pathway, but does not require de novo protein synthesis.

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