Steroid pretreatment improves graft recovery in a sheep orthotopic heart transplantation model.
BACKGROUND
Previous reports provide conflicting evidence concerning effects of steroids on recovery of cardiac function during procedures involving cardiopulmonary bypass. This study was designed to test the hypothesis that pretreatment of animals with steroids before heart transplantation improves graft hemodynamic function.


METHODS
Four groups of sheep were studied: CON, nonsteroid-treated nontransplanted controls (n = 8); CON-S, steroid-treated nontransplanted controls (n = 5); TX, nonsteroid-treated transplanted animals (n = 5); and TX-S, steroid-treated transplanted animals (n = 5). Steroid-treated animals were given methylprednisolone 30 mg/kg immediately before surgery. Procedures for harvest and orthotopic transplantation were similar to those used clinically. Contractile function, left ventricular diameter, and cardiac 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 pretreatment produced significantly higher function in controls and transplanted animals compared with nonsteroid-treated animals. On average over 6 hours, significant steroid effects were observed for left ventricular 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 transplanted animals. All five TX-S animals could be removed from inotropic 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 PO2 values were significantly higher in steroid-treated animals than in nonsteroid treated animals. Blood systemic lactate, which was elevated after transplantation, returned to control level by 6 hours in the steroid-treated group but not in the nonsteroid-treated group.


CONCLUSIONS
Steroid pretreatment of heart donors and recipients improved systolic and diastolic function and hemodynamic stability after transplantation. In addition, steroid pretreatment improved pulmonary gas exchange of control and transplanted animals.
Segel
L D
LD
Division of Cardiothoracic Surgery, University of California School of Medicine, Davis 95616-8606, USA.
Follette
D M
DM
Castellanos
L M
LM
Hayes
R
R
Baker
J M
JM
Smolens
I V
IV
D000818:Animals; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D009200:Myocardial Contraction / Q000187:drug effects / Q000276:immunology; D011292:Premedication; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects / Q000276:immunology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000276:immunology
D008775:Methylprednisolone