title: Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium.
abstract: OBJECTIVE
  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 x 5 min PC, group 2) or subthreshold PC stimulus (2 x 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 x 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.
authors.affiliation: Department of Experimental Surgery, PTE, Pécs, Hungary.
authors.forename: M T
authors.initials: MT
authors.lastname: Jaberansari
authors.forename: G F
authors.initials: GF
authors.lastname: Baxter
authors.forename: C A
authors.initials: CA
authors.lastname: Muller
authors.forename: S E
authors.initials: SE
authors.lastname: Latouf
authors.forename: E
authors.initials: E
authors.lastname: Röth
authors.forename: L H
authors.initials: LH
authors.lastname: Opie
authors.forename: D M
authors.initials: DM
authors.lastname: Yellon
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac; D005260:Female; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction; D013552:Swine; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors