Endocardial and epicardial infarct size after preconditioning by a partial coronary artery occlusion without intervening reperfusion. Importance of the degree and duration of flow reduction

OBJECTIVE: Recently, we reported that a partial coronary artery occlusion immediately preceding a sustained coronary artery occlusion limited infarct size. We now investigated whether the protection by partial coronary artery occlusions (i) depends on the severity and(or) duration of the flow reduction and (ii) varies in the different myocardial layers. METHODS: In 71 open-chest pigs (eight groups) left ventricular area at risk (AR) and infarct area (IA) were determined for the endocardial (IAendo and ARendo) and epicardial halves (IAepi and ARepi). RESULTS: In control animals (60 min total coronary artery occlusion (TCO) followed by 120 min reperfusion (Rep)) there were highly linear relations between IA and AR in the endocardium (r = 0.98, P < 0.01) and epicardium (r = 0.97, P < 0.01), which could be described by IAendo = 1.01 ARendo - 4.5 and by IAepi = 0.88ARepi - 3.6, respectively. In animals that underwent a 10 min TCO + 15 min Rep prior to the 60 min TCO + 120 min Rep, IA in both myocardial layers were again highly linearly related with AR, with less steep slopes for both the endocardium (0.63) and epicardium (0.57) (both P < 0.01). Two groups of pigs were subjected to either a 30 or 90 min 70% reduction in coronary blood flow (FR) immediately preceding the 60 min TCO + 120 min Rep, without intervening reperfusion. A 30 min 70% FR decreased IA to the same degree in the endo- and epicardial half. A 90 min 70% FR resulted in protection in the epicardium (P < 0.01) but not in the endocardium, most likely because 90 min 70% FR without 60 min TCO already caused infarction which was more severe in the endo- than in the epicardium (P < 0.01). Endocardial and epicardial IA after either a 30 or 90 min 30% FR prior to the 60 min TCO was not different from that in the control group, indicating that this mild flow reduction failed to limit irreversible damage. CONCLUSIONS: Thirty or ninety min of severe (70%) but not mild (30%) coronary flow reductions protected against myocardial infarction. The protection by a 70% FR was influenced by the duration of FR as a 30 min 70% FR similarly decreased IA in the endocardial and epicardial halves, while 90 min 70% FR preferentially limited IA in the epicardial half. These findings suggest that perfusion abnormalities immediately preceding an infarction could be an important source of infarct size variability in patients.