F-18 2-DEOXYGLUCOSE DEPOSITION AND REGIONAL FLOW IN PIGS WITH CHRONICALLY DYSFUNCTIONAL MYOCARDIUM - EVIDENCE FOR TRANSMURAL VARIATIONS IN CHRONIC HIBERNATING MYOCARDIUM

Background Hibernating myocardium in patients with collateral-dependen t myocardium is characterized by relative reductions in resting flow a nd increases in the uptake of F-18-2-deoxyglucose (FDG) in the fasting state. We performed the present study to examine whether these key ph ysiological alterations could be produced in a porcine model of chroni c coronary occlusion and to assess whether the adaptations consistent with hibernation varied across the myocardial wall. Methods and Result s We chronically instrumented pigs (n=18) with a fixed occluder on the proximal left anterior descending coronary artery (LAD). Three months later, ventricular function, regional myocardial perfusion, and FDG d eposition (by excised tissue counting or positron emission tomography) were assessed in pigs after an overnight fast in the closed-chest ane sthetized state. Total LAD occlusion with angiographic collaterals was present in the majority of animals, Left ventriculography showed seve re anterior hypokinesis, and resting perfusion was significantly reduc ed in the hibernating LAD region in comparison with the normal remote regions (subendocardium: 0.80+/-0.06 versus 1.07+/-0.06 mL . min(-1) . g(-1), P<.001; full-thickness: 0.87 +/- 0.04 versus 0.99 +/- 0.06 mL . min(-1) . g(-1), P<.01). There was a twofold increase in full-thickn ess fasting FDG uptake in the dysfunctional LAD region (1.8+/-0.2 by p ositron emission tomography versus 1.9+/-0.1 by ex vivo counting). Ex vivo tissue counting revealed a pronounced transmural variation in FDG uptake In the hibernating region (LAD/ normal), which averaged 2.5+/- 0.2 in the subendocardium, 1.9+/-0.2 in the midmyocardium, and 1.4+/-0 .1 in the subepicardium. Conclusions These results demonstrate that pi gs instrumented with a proximal LAD stenosis develop hibernating myoca rdium characterized by relative reductions in resting function and per fusion in association with increased uptake of FDG in the fasting stat e. The transmural variations in relative resting flow and FDG uptake s uggest that myocardial adaptations consistent with hibernation are mos t pronounced in the subendocardial layers and vary in relation to loca l coronary flow reserve.