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  • Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury.

Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury.

Circulation (2010-09-21)
Javier A Sala-Mercado, Joseph Wider, Vishnu Vardhan Reddy Undyala, Salik Jahania, Wonsuk Yoo, Robert M Mentzer, Roberta A Gottlieb, Karin Przyklenk
ABSTRACT

Emerging evidence suggests that "adaptive" induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction. Anesthetized pigs underwent 45 minutes of coronary artery occlusion and 3 hours of reperfusion. In the first component of the study, pigs received chloramphenicol succinate (CAPS) (an agent that purportedly upregulates autophagy; 20 mg/kg) or saline at 10 minutes before ischemia. Infarct size was delineated by tetrazolium staining and expressed as a % of the at-risk myocardium. In separate animals, myocardial samples were harvested at baseline and 10 minutes following CAPS treatment and assayed (by immunoblotting) for 2 proteins involved in autophagosome formation: Beclin-1 and microtubule-associated protein light chain 3-II. To investigate whether the efficacy of CAPS was maintained with "delayed" treatment, additional pigs received CAPS (20 mg/kg) at 30 minutes after occlusion. Expression of Beclin-1 and microtubule-associated protein light chain 3-II, as well as infarct size, were assessed at end-reperfusion. CAPS was cardioprotective: infarct size was 25±5 and 41±4%, respectively, in the CAPS-pretreated and CAPS-delayed treatment groups versus 56±5% in saline controls (P<0.01 and P<0.05 versus control). Moreover, administration of CAPS was associated with increased expression of both proteins. Our results demonstrate attenuation of ischemia-reperfusion injury with CAPS and are consistent with the concept that induction of autophagy may provide a novel strategy to confer cardioprotection.

MATERIALS
Product Number
Brand
Product Description

Chloramphenicol sodium succinate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Chloramphenicol succinate sodium salt, ≥80% (HPLC)