An experimental model of chronic myocardial hibernation

Background. Hibernating myocardium describes persistently impaired ventricu lar function at rest caused by reduced coronary blood flow. However, a real istic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernati on could be produced in swine. Methods. Miniswine underwent 90% stenosis of the left circumflex coronary a rtery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chlorid e assessed percent infarction. Electron microscopy was used to identify cel lular changes characteristic of hibernating myocardium. Results. Positron emission tomography (N-13-labeled-ammonia) 3 days after o cclusion demonstrated a significant reduction in myocardial blood flow in t he left circumflex distribution. This reduced flow was accompanied by incre ased glucose use (F-18-fluorodeoxyglucose), which is consistent with hibern ating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left ci rcumflex distribution. Dobutamine stress echocardiography 3 days after occl usion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride stai ning (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at-risk lo calized to the endocardial surface. Electron microscopy (n = 4) 14 days aft er occlusion demonstrated loss of contractile elements and large areas of g lycogen accumulation within viable cardiomyocytes, also characteristic of h ibernating myocardium. Conclusions. Chronic low-now myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the u se of therapies designed to improve blood flow to the heart. (C) 2000 by The Society of Thoracic Surgeons.