title: Myocardial infarct size is smaller in dogs with pacing-induced heart failure.
abstract: OBJECTIVE
  Determine if ischemic tolerance is reduced in the setting of experimental heart failure (HF).
  
  
  METHODS
  Dogs were paced for 3 weeks at 240 BPM to induce heart failure which was confirmed with hemodynamic and echocardiographic measurements. The pacemaker was turned off 30 min prior to the ischemia study. Normal (n = 9) and HF dogs (n = 12) were anesthetized with sodium pentobarbital, instrumented for cardiovascular assessment through a left lateral thoracotomy, and myocardial blood flow was measured with radioactive microspheres. The left circumflex (LCX) artery was occluded for 90 min followed by 3 h of reperfusion. Infarct size was determined with triphenyl tetrazolium chloride staining.
  
  
  RESULTS
  Two-dimensional echocardiograms were obtained before and after 3 weeks of pacing in the HF group. Ejection fraction was reduced from 67 +/- 1 to 32 +/- 2% (P < 0.001) and left ventricular end-diastolic volume (LVEDV) increased from 29 +/- 4 ml before pacing to 47 +/- 5 ml (P < 0.001). HF dogs were characterized by a smaller peak positive dP/dt (1110 +/- 72 vs. 2546 +/- 41 mmHg/s, P < 0.01), a greater LV end-diastolic pressure (34 +/- 3 vs. 9 +/- 2 mmHg, P < 0.01), and lower LV end-systolic pressure (99 +/- 5 vs. 130 +/- 5 mmHg, P < 0.05) compared to control dogs. Heart rate was not significantly different between the two groups throughout the experiment. More HF dogs died from ventricular fibrillation (4/12) than control dogs (1/9), but this difference was not statistically significant (P > 0.2). The LCX occlusion produced a comparable decrease in blood flow in HF and normal dogs (0.08 +/- 0.01 vs. 0.09 +/- 0.01 ml/min/g), but infarct size as a percentage of the region at risk was smaller in HF dogs compared to normal dogs (21 +/- 4 vs. 45 +/- 4%, P < 0.01). Region at risk size was also smaller in HF versus normal dogs (29 +/- 3 vs. 40 +/- 2%, P < 0.05). Accordingly, a subgroup analysis of 6 HF and 5 control dogs with similar RAR sizes (35 +/- 2% vs. 37 +/- 2%) was performed and it also demonstrated that infarct size in HF dogs was smaller than in control dogs (19 +/- 5 vs. 40 +/- 4%, P < 0.01), suggesting that disparities in risk region size did not explain the differences in infarct size.
  
  
  CONCLUSIONS
  Infarct size produced by a standardized ischemia-reperfusion protocol was smaller in dogs with pacing-induced HF. The reduced extent of infarction could not be attributed to differences in collateral blood flow or the size of the region at risk. Although the hearts in HF dogs were dilated, LV systolic blood pressure and the strength of contraction were lower than controls potentially reducing myocardial oxygen demand and explaining the smaller infarct size in HF dogs. Other mechanisms, however, cannot be discounted. Thus, ischemic tolerance is not reduced and may be augmented in dogs with pacing-induced heart failure.
authors.affiliation: Department of Cardiovascular Therapeutics, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Hoskins
authors.forename: D P
authors.initials: DP
authors.lastname: Ignasiak
authors.forename: L J
authors.initials: LJ
authors.lastname: Saganek
authors.forename: K P
authors.initials: KP
authors.lastname: Gallagher
authors.forename: J T
authors.initials: JT
authors.lastname: Peterson
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D004285:Dogs; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*