Profound Cardioprotection With Chloramphenicol Succinate in the Swine Model of Myocardial Ischemia-Reperfusion Injury

• DOI: 10.1161/circulationaha.109.928242
• Publication Date: 2010-09-13T21:03:47Z
• Authors: Javier A. Sala-Me...; Joseph Wider; Vishnu Vardhan Re...; Salik Jahania; Wonsuk Yoo; Robert M. Mentzer; Roberta A. Gottlieb; Karin Przyklenk
• Keywords: Cardioprotection

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