MYOCARDIAL INFARCT SIZE IS SMALLER IN DOGS WITH PACING-INDUCED HEART-FAILURE

Objective: Determine if ischemic tolerance is reduced in the setting o f experimental heart failure (HF). Methods: Dogs were paced fur 3 week s at 240 BPM to induce heart failure which was confirmed with hemodyna mic and echocardiographic measurements. The pacemaker was turned off 3 0 min prior to the ischemia study. Normal (n = 9) and KF dogs (n = 12) were anesthetized with sodium pentobarbital, instrumented for cardiov ascular assessment through a left lateral thoracotomy, and myocardial blood flow was measured with radioactive microspheres. The left circum flex (LCX) artery was occluded for 90 min followed by 3 h of reperfusi on. Infarct size was determined with triphenyl tetrazolium chloride st aining. Result: Two-dimensional echocardiograms were obtained before a nd after 3 weeks of pacing in the HF group. Ejection fraction was redu ced from 67 +/- 1 to 32 +/- 2% (P < 0.001) and left ventricular end-di astolic volume (LVEDV) increased from 29 +/- 4 ml before pacing to 47 +/- 5 ml (P < 0.001). HF dugs were characterized by a smaller peak pos itive dP/dt (1110 +/- 72 vs. 2546 +/- 411 mmHg/s, P < 0.01), a greater LV end-diastolic pressure (31 +/- 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 fr om ventricular fibrillation (4/12) than control dogs (1/9), but this d ifference was not statistically significant (P > 0.2). The LCX occlusi on 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 perc entage 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 does with simil ar RAR sizes (35 +/- 2% vs. 37 +/- 2%) was performed and it also demon strated that infarct size in HF dogs was smaller than in control does (19 +/- 5 vs. 40 +/- 4%, P < 0.01), suggesting that disparities in ris k region size did not explain the differences in infarct size. Conclus ion: Infarct size produced by a standardized ischemia-reperfusion prot ocol 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 dog s were dilated, LV systolic blood pressure and the strength of contrac tion were lower than controls potentially reducing myocardial oxygen d emand and explaining the smaller infarct size in HF dogs. Other mechan isms, however, cannot be discounted. Thus, ischemic tolerance is. not reduced and may be augmented in dogs with pacing-induced heart failure .