Studies on the Coronary Circulation during Rejection of the Heterotopically Transplanted Dog Heart

Abstract

Coronary blood flow and vascular reactivity were studied at intervals after donor dog hearts were transplanted into the necks of recipient dogs. Coronary blood flow was measured with an electromagnetic flow transducer on the carotid artery of the recipient dog, and coronary vascular reactivity was assessed from the response of the coronary vessels to the vasodilator drugs, dipyridamole and adenosine. During the first 4 days after the transplant, resting coronary blood flow and vascular resistance did not change. Responses to dipyridamole and adenosine were unchanged during the first 2 days but were reduced on the third and fourth days. Increased vascular permeability to circulating Evans blue dye and deposition of colloidal carbon in venules occurred in association with small increases in left ventricular myocardial water content 3 and 4 days after the transplant. These changes indicate that an inflammatory response accompanies the onset of histological evidence of rejection at 3 and 4 days. The reduced vascular reactivity of the transplanted heart at 3 and 4 days may be related to morphological changes in arterioles rather than to gross edema formation during rejection. KEY WORDScoronary blood flow Evans blue dye coronary vascular reactivity permeability studies in the heart dipyridamole acute rejection adenosine colloidal carbon transplantation• The early phase of acute rejection of organ allografts is accompanied by evidence of increased vascular permeability (1, 2) and mononuclear cell infiltration. Similar changes are present in the early rejection of the transplanted heart (3-5), indicating alterations in the walls of the coronary blood vessels. The response of these altered vessels to coronary vasodilator drugs is not known but may be of clinical importance in the management of rejection crises associated with a reduced coronary blood flow (6). In earlier studies we have shown that the response of the coronary vasculature to vasodilator drugs is normal in the immediate posttransplantation period (7,8). In the present study, we measured the coronary blood flow in the heart from the time of the transplant until there was early histological evidence of rejection and we assessed coronary vascular reactivity by recording the increases in coronary blood flow produced by the vasodilator drugs, dipyridamole and adenosine. Changes in coronary artery reactivity were correlated with histopathological changes and permeability studies in coronary arterial and cardiac microcirculation in the early phases of rejection. Methods EXPERIMENTAL MODELThe donor dog's heart was transplanted into the neck of the recipient dog according to a modification of the technique described previously (7). All the dogs were anesthetized with sodium thiopental (20 mg/kg, iv) and maintained on a gas mixture of nitrous oxide and oxygen (2:1). The recipient dogs (20-25 kg) also received halothane (0.5-1.0%).The neck of the recipient dog was dissected to expose the carotid artery and the external jugular vein. Arterial and venous polyvi...