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Isograft studies were performed in the murine model of cardiac transplantation to investigate the morphologic effects of operative ischemia. Primarily vascularized CBA mouse hearts were grafted heterotopically into the recipient CBA mouse's abdomen with standard microsurgical techniques. After ischemia times of 30 and 60 minutes, histologic examination showed minimal myocardial damage, with necrosis or scarring occupying less than 5% of the cross-sectional area of hearts bisected from apex to base after grafts had been removed on the seventh day after transplantation. Maximal ischemic damage was seen at 7 days after transplantation after 120 minutes of ischemia, with more than 30% myocardial necrosis or scarring of myocardial tissue. Isografts performed with ischemia times of less than 60 minutes were followed for more than 100 days. All hearts showed a fine, generalized, perimyocytic fibrosis, which was maximal at 28 days after transplantation and did not progress thereafter. These results will serve as important control measures for future studies in this model because ischemic damage must be considered in examining histologic samples from long-surviving cardiac allografts maintained in immunosuppressed recipients.