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

96 Citations (Scopus)

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)
JournalCirculation
Volume122
Issue number11 SUPPL. 1
DOIs
StatePublished - Sep 14 2010

Fingerprint

Myocardial Reperfusion Injury
Reperfusion Injury
Myocardial Ischemia
Swine
Autophagy
Microtubule-Associated Proteins
Reperfusion
chloramphenicol succinate
Light
Coronary Occlusion
Recycling
Immunoblotting
Organelles
Proteolysis
Coronary Vessels
Myocardium
Proteins
Up-Regulation
Ischemia
Animal Models

Keywords

  • autophagy
  • ischemia
  • myocardial infarction
  • reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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

Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury. / Sala-Mercado, Javier A.; Wider, Joseph; Reddy Undyala, Vishnu Vardhan; Jahania, Salik; Yoo, Wonsuk; Mentzer, Robert M.; Gottlieb, Roberta A.; Przyklenk, Karin.

In: Circulation, Vol. 122, No. 11 SUPPL. 1, 14.09.2010.

Research output: Contribution to journalArticle

Sala-Mercado, JA, Wider, J, Reddy Undyala, VV, Jahania, S, Yoo, W, Mentzer, RM, Gottlieb, RA & Przyklenk, K 2010, 'Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury', Circulation, vol. 122, no. 11 SUPPL. 1. https://doi.org/10.1161/CIRCULATIONAHA.109.928242
Sala-Mercado, Javier A. ; Wider, Joseph ; Reddy Undyala, Vishnu Vardhan ; Jahania, Salik ; Yoo, Wonsuk ; Mentzer, Robert M. ; Gottlieb, Roberta A. ; Przyklenk, Karin. / Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury. In: Circulation. 2010 ; Vol. 122, No. 11 SUPPL. 1.
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AU - Jahania, Salik

AU - Yoo, Wonsuk

AU - Mentzer, Robert M.

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