Diastolic function in the heterotopic rat heart transplant model: Effects of edema, ischemia, and rejection

Decreased systolic ventricular function and compliance and increased left ventricular edema and mass have been demonstrated in cardiac allograft rejection. Whether decreased left ventricular compliance in rejection is caused by myocardial edema has not been examined, and compliance in the Ono-Lindsey model has not been reported. Heterotopic rat abdominal cardiac transplantation was performed in ACI isografts (n = 24) and in ACI to Lewis allografts (n = 24). Subgroups were studied on posttransplantation days O, 1, 3, and 5 (each n = 6). Both transplanted hearts and native hearts were arrested with potassium for the assessment of myocardial water content, heart weight, and the left ventricular pressure-volume relation. In transplanted hearts, myocardial water content did not change in isografts but increased on posttransplantation day 5 in allografts (81.1 % on posttransplantation day 5 versus 76.1 % on day O, 77.2 % on day 1, and 77.5 % on day 3, p < 0.05). Wet and dry heart weight also increased on posttransplantation day 5 in allografts (p < 0.05). The left ventricular pressure-volume relation in transplanted hearts shifted to the left when compared with that in native hearts in all subgroups; these volume differences were statistically significant (p < 0.01) for all pressures above 7.5 mm Hg. This pattern was similar in isografts and allografts on posttransplantation days O, 1, and 3, and no significant differences between isografts and allografts were demonstrated. On posttransplantation day 5, however, the pressure after a 0.05 ml injection in allografts was greater in transplanted hearts than in native hearts (24 ± 3 versus 3 ± 1 mm Hg, p < 0.01). The pressure difference between transplanted and native hearts was also significantly greater in allografts than in isografts (22 ± 2 versus 6 ± 1 mm Hg, p < 0.01), indicating an increase in stiffness of allografts. Thus edema and impaired diastolic properties occur concurrently with allograft rejection. Left ventricular volume is abnormal from posttransplantation days 0 to 5 in transplanted hearts but not native hearts in the Ono-Lindsey model with current methods, apparently because of ischemic injury during transplantation.