title: Hemorrhage induces acute cardioadaptation to ischemia-reperfusion by an alpha1-adrenoceptor-mediated, protein synthesis-independent mechanism.
abstract: 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.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: J C
authors.initials: JC
authors.lastname: Cleveland
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: B C
authors.initials: BC
authors.lastname: Sheridan
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation; D003513:Cycloheximide / Q000494:pharmacology; D003971:Diastole; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D011224:Prazosin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013997:Time Factors
chemical_list: D000317:Adrenergic alpha-Antagonists; D011500:Protein Synthesis Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D003513:Cycloheximide; D011224:Prazosin