Hemorrhage induces acute cardioadaptation to ischemia-reperfusion
by an [alpha]1-adrenoceptor mediated, protein synthesis independent
mechanism.
Meldrum, Daniel R., Joseph C. Cleveland, Jr., Xianzhong Meng, Brett C.
Sheridan, Anirban Banerjee, Alden H. Harken.
Department of Surgery, University of Colorado Health Sciences
Center, Denver, Colorado
APStracts 3:0390R, 1996.
Hemorrhage and resuscitation (H/R) has been recognized as an
exclusively destructive process which 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, [alpha]1
-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 [alpha]1-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 [alpha]1-adrenoceptors;
and 3) whether H/R induced endogenous adaptation requires de novo
protein synthesis. Rats were hemorrhaged and resuscitated (H/R+I/R),
sham operated (Sham H/R+I/R), or neither (I/R alone), with and
without prior [alpha]1-adrenoceptor or protein synthesis inhibition.
Hearts were then isolated and subjected to a second insult consisting
of global, normothermic I/R (20 min/40 min). The results show that
antecedent H/R improved post-I/R left ventricular developed pressure
(DP), compliance (EDP), coronary flow (CF), and decreased reperfusion
creatine kinase (CK) loss (P<0.05, ANOVA with Bonferroni
-Dunn). H/R induced adaptation was abolished by prior [alpha]1
-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 [alpha]1-adrenergic signalling pathway, but
does not require de novo protein synthesis.
Received 18 July 1996; accepted in final form 25 October 1996.
APS Manuscript Number R414-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996