Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium

M. T. Jaberansari, Gary F. Baxter, Cecile A. Muller, Sean E. Latouf, E. Röth, Lionel H. Opie, Derek M. Yellon

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

OBJECTIVES: We assessed the effect of angiotensin-converting enzyme (ACE) inhibition in combination with a subthreshold preconditioning (PC) stimulus to elicit delayed preconditioning against infarction in pig myocardium. BACKGROUND: Bradykinin triggers early PC. Angiotensin-converting enzyme inhibitors increase local bradykinin levels via inhibition of kinin breakdown and have been shown in experimental studies to augment early protection afforded by PC. A role for bradykinin in eliciting delayed PC has not so far been identified. METHODS: We used a two-day protocol. On day 1 (closed chest), pigs were either sham-operated (group 1) or preconditioned, using balloon catheter inflation of the left anterior descending (LAD) coronary artery, with either a full (4 × 5 min PC, group 2) or subthreshold PC stimulus (2 × 2 min PC, group 3). Additional groups were pre-treated with perindoprilat (0.06 mg/kg i.v.) before sham (group 4) or subthreshold PC (group 5). On day 2 (open chest), all pigs were subjected to 40 min occlusion of the LAD followed by 3 h of reperfusion. Infarct size was determined by tetrazolium staining. RESULTS: Group 1 had a mean infarct size of 42.8 ± 3.2% of the risk zone. Preconditioning with 4 × 5 min reduced the infarct size to 19.5 ± 3.9% (p < 0.05). Groups 3 and 4 had infarct sizes not statistically different from group 1. However, combining perindoprilat with subthreshold PC resulted in a significant limitation of the infarction (18.4 ± 3.1% p < 0.05), comparable with group 2. CONCLUSIONS: This is the first study to show that ACE inhibition can augment a mild ischemic stimulus to induce a protected state 24 h later.

Original languageEnglish
Pages (from-to)1996-2001
Number of pages6
JournalJournal of the American College of Cardiology
Volume37
Issue number7
DOIs
Publication statusPublished - Jun 1 2001

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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