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In cardiac allograft rejection, histopathologic changes suggesting that myocardial ischemia is a component of the rejection process have been documented. To further define the coronary vascular reactivity of human heart transplant, coronary sinus blood flow and coronary resistance were measured before and after intravenous dipyridamole within the first year after transplantation in 8 patients without rejection (group II) and in 5 patients with rejection (group III). All had normal coronary arteriograms. Results were compared to those of 8 control subjects (group I). After dipyridamole, coronary sinus blood flow was increased in groups I, II and III by 303, 212 (p [is than]0.01 vs group I) and 45%, respectively (p [is less than]0.001 vs groups I and II). Coronary resistance was reduced by 77, 73 (not significant vs goup I) and 36%, respectively (p [is less than]0.001 vs groups I and II). Concomitantly, coronary sinus blood oxygen content was increased by 172, 145 (not significant vs group I) and 78%, respectively (p [is less than]0.001 vs group I, not significant vs group II). Thus, the coronary flow reserve evaluated by the dipyridamole/basal coronary sinus blood flow ratio and the coronary resistance reserve evaluated by the basal/dipyridamole coronary resistance ratio were dramatically impaired in group III (1.56 [+ or -] 0.09 and 1.6 [+ or -] 0.30, respectively, p [is less than]0.001 vs groups I and II). In contrast, they were almost normal in group II (3.11 [+ or -] 0.42 vs. 4.03 [+ or -] 0.52 in group I, p [is less than ]0.02, and 3.83 [+ or -] 0.78 vs. 4.45 [+ or -] 0.81 in group I, difference not significant). Thus, the impairment of coronary reserve during heart rejection should be linked to abnormalities of the coronary microvasculature. This emphasizes the important involvement of the coronary circulation in the rejection process., Coronary circulation, which nourishes the heart muscle, is known to play an important role in the success of a heart transplant. For example, it is thought that the organ rejection process is related to myocardial ischemia (MI; heart attack caused by inadequate oxygen supply to the heart usually due to a blockage in a coronary artery). Changes in heart tissues which were influential in coronary blood flow and coronary resistance were examined in 19 subjects. Three groups were identified; group I consisted of eight normal individuals without symptoms of heart disease, group II was made up of eight patients who recently had a heart transplant and showed no histologic (cellular) symptoms of rejection, and group III was comprised of five recent heart transplant patients who were exhibiting histologic signs of rejection. Baseline measurements of all subjects were taken before and after the administration of dipyridamole, a vasodilator i.e., an agent which causes the relaxation of the blood vessels. All measurements were taken within one year of heart transplantation. Coronary blood flow and coronary resistance were recorded and quantitatively analyzed in all three groups. No significant differences were observed between the normal group and the asymptomatic transplant group. However, the transplant group which showed with histological irregularities had dramatically impaired capacities when blood flow ratios and coronary resistance ratios were calculated. The results of this study emphasized the importance of coronary circulation as a factor in rejection. Further research in this area is considered to be important because of the potential reversibility of these conditions via treatments which may aid in reducing heart transplant rejections.