STEROID PRETREATMENT IMPROVES GRAFT RECOVERY IN A SHEEP ORTHOTOPIC HEART-TRANSPLANTATION MODEL

Background: Previous reports provide conflicting evidence concerning e ffects of steroids on recovery of cardiac function during procedures i nvolving cardiopulmonary bypass. This study was designed to test the h ypothesis that pretreatment of animals with steroids before heart tran splantation improves graft hemodynamic function. Methods: Four groups of sheep were studied: CON, nonsteroid-treated nontransplanted control s (n = 8); CON-S, steroid-treated nontransplanted controls (n = 5); TX , nonsteroid-treated transplanted animals (n = 5); and TX-S, steroid-t reated transplanted animals (n = 5). Steroid-treated animals were give n methylprednisolone 30 mg/kg immediately before surgery. Procedures f or harvest and orthotopic transplantation were similar to those used c linically. Contractile function, left ventricular diameter, and cardia c output of control and transplanted hearts were measured for 6 hours. A 2 x 2 factorial repeated measures analysis of variance was used to determine statistical significance (p < 0.05). Results: Steroid pretre atment produced significantly higher function in controls and transpla nted animals compared with nonsteroid-treated animals. On average over 6 hours, significant steroid effects were observed for left Ventricul ar peak systolic pressure, mm Hg (CON, 85 +/- 2; CON-S, 98 +/- 3; TX, 74 +/- 3; TX-S, 91 +/- 2); global stroke work, mJoule x cm(-2) (CON, 4 .69 +/- 0.21; CON-S, 5.88 +/- 0.32; TX, 2.27 +/- 0.17; TX-S, 4.23 +/- 0.16); and peak rate of pressure relaxation (-dP/dt(max)), mm Hg/msec (CON, 1.23 +/- 0.05; CON-S, 1.44 +/- 0.08; TX, 0.60 +/- 0.03; TX-S, 2. 04 +/- 0.13). Steroid pretreatment produced more stable recovery for t ransplanted animals. All five TX-S animals could be removed from inotr opic support and had stable function for 6 hours. In contrast, 1 of 5 TX animals could not be removed from inotropic support, and 1 of 5 TX hearts failed 3 hours after transplant. Arterial blood po, values were significantly higher in steroid-treated animals than in nonsteroid tr eated animals. Blood systemic lactate, which was elevated after transp lantation, returned to control level by 6 hours in the steroid-treated group but not in the nonsteroid-treated group. Conclusion: Steroid pr etreatment of heart donors and recipients improved systolic and diasto lic function and hemodynamic stability after transplantation. In addit ion, steroid pretreatment improved pulmonary gas exchange of control a nd transplanted animals.