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Cardioprotective effect of δ-opioid receptor agonist vs mild therapeutic hypothermia in a rat model of cardiac arrest with extracorporeal life support.
MedLine Citation:
PMID:  22771872     Owner:  NLM     Status:  Publisher    
BACKGROUND: To compare the effect of δ-opioid receptor agonist, d-Ala2-d-Leu5 enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function in a model of extracorporeal life support (ECLS). METHODS: Ventricular fibrillation (VF) was induced in male Wistar rats. After 10min of untreated VF, venoarterial ECLS was instituted for 60min. At the beginning of ECLS animals were randomized to three groups of ten: normothermia, hypothermia (32°C) and DADLE intravenous infusion (1mg/kg/h). Cooling to 32°C or normothermia or drug infusion lasted for the entire ECLS. Plasma samples and myocardial biopsies were obtained and left-ventricular (LV) function was assessed by a conductance catheter at baseline and after weaning from ECLS. RESULTS: DADLE administration resulted in a significantly enhanced recovery of LV systolic function expressed by slope of the LV end-systolic pressure volume relationship (Ees) and Preload recruitable stroke work (PRSW) than hypothermia and normothermia. LV stiffness indicated by end-diastolic pressure volume relationship (EDPVR) was significantly lower after DADLE administration (P< 0.01). LV relaxation described by Tau was preserved after DADLE treatment but not after normothermia or mild hypothermia (P< 0.01). Plasma lactate concentrations were lower in DADLE group (P< 0.05). DADLE and not conventional hypothermia significantly increased phosphorylation of the kinases ERK1 and 2 (3.9±0.3 and 3.1±0.5 vs 0.4±0.1 and 0.3±0.1-fold of baseline levels) (P< 0.001). Both DADLE and hypothermia but not normothermia increase phosphorylation of Akt. CONCLUSIONS: DADLE was more effective than mild therapeutic hypothermia in recovering myocardial function and activation of the pro-survival kinases Akt and ERK after ECLS.
Alessio Rungatscher; Daniele Linardi; Alice Giacomazzi; Maddalena Tessari; Tiziano Menon; Alessandro Mazzucco; Giuseppe Faggian
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-5
Journal Detail:
Title:  Resuscitation     Volume:  -     ISSN:  1873-1570     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0332173     Medline TA:  Resuscitation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Department of Surgery, Division of Cardiac Surgery, University of Verona, Verona, Italy.
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