Comparison of myocardial oxygen consumption using C-11 acetate positron emission tomography scanning in a working and non-working heart transplant model

Objective: In acute cardiac rejection, changes in myocardial oxygen consump tion occur; non-invasive detection of these metabolic changes would have ob vious clinical utility. In the classic cervical, heterotopic, canine, trans plant model, the heart is non-working. It has a low myocardial oxygen consu mption. Creation of a working model with normal myocardial oxygen consumpti on would enhance validity of non-human studies, Methods: Clearance of C-11 acetate was determined by positron emission tomography (PET) scanning and c ompared with myocardial oxygen consumption in normal and transplanted canin e hearts. Donor hearts from mongrel dogs (2.5-3 kg; n = 4) were transplante d into the neck of adult beagles (12-15 kg; n = 4), no immunosuppression wa s given. Two non-working hearts were modified to eject only coronary flow v ia the right ventricle. In two hearts, a novel working model was created wi th aortic regurgitation to load the left ventricle. Working and non-working hearts underwent PET scanning on post-operative days 2 and 4. Normal dog h earts (n = 2) and native hearts of transplanted dogs (n = 3) were used to v alidate the scanning technique. Coronary sinus and aortic oxygen saturation data along with myocardial blood flow (radiolabeled microspheres) confirme d that clearance of C-11 acetate in normal and transplanted hearts followed a biexponential model. Results: Myocardial oxygen consumption was correlat ed with the rate constant of C-11 acetate rapid phase clearance (r = 0.91) in normal and transplanted hearts. The working hearts had increased myocard ial oxygen consumption compared to non-working hearts. Conclusions: This st udy (1) introduces a model of a working heterotopic cardiac transplantation with near-normal oxygen consumption; and (2) demonstrates that regional my ocardial oxygen consumption in transplanted hearts can be detected by C-11 acetate PET. (C) 2001 Elsevier Science B.V. All rights reserved.