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

Javier A. Sala-Mercado, Joseph Wider, Vishnu Vardhan Reddy Undyala, Salik Jahania, Wonsuk Yoo, Robert M. Mentzer, Roberta A. Gottlieb, Karin Przyklenk

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Background-: 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. Methods and results-: 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. Conclusion-: 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.

Original languageEnglish (US)
Pages (from-to)S179-S184
JournalCirculation
Volume122
Issue number11 SUPPL. 1
DOIs
StatePublished - Sep 14 2010

Keywords

  • autophagy
  • ischemia
  • myocardial infarction
  • reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Sala-Mercado, J. A., Wider, J., Reddy Undyala, V. V., Jahania, S., Yoo, W., Mentzer, R. M., Gottlieb, R. A., & Przyklenk, K. (2010). Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury. Circulation, 122(11 SUPPL. 1), S179-S184. https://doi.org/10.1161/CIRCULATIONAHA.109.928242