Improved right ventricular function after intracoronary administration of a C1 esterase inhibitor in a right heart transplantation models

Objective: Myocardial injury from ischemia can be augmented after reperfusi on due to proinflammatory events including complement activation, leukocyte adhesion, and release of various chemical mediators. It has been shown tha t intracoronary administration of a C1 esterase inhibitor (C1 INH) signific antly reduces myocardial necrosis in an experimental model of ischemia. Our study addresses the question whether the most susceptible region of the he art for ischemic injury, the right ventricle (RV), can benefit from the pro tective effects of C1 esterase inhibition after transplantation. Methods: T o precisely control RV volume in vivo an isovolumic model was used in which the RV volume was regulated using an intracavity high compliance balloon i nserted into donor hearts of domestic pigs (34 +/- 4 kg). After 4 h of isch emia, donor hearts were transplanted into recipient pigs (44 +/- 4 kg). Tre atment groups, each with six animals, consisted of C1 INH treatment or cont rol. After opening the cross clamp, the C1 INH group animals received 20 IU /kg body weight of C1 INH intracoronary over a 5 min period. The control an imals received no drug therapy. The hearts were reperfused for 60 min, and thereafter the RV balloon volume was increased in 10 ml increments until RV failure occurred. These measurements were repeated after 120 min of reperf usion. Results: There was no significant difference in maximal RV developed pressure between the two groups (after 1 h, 35.7 +/- 5.9 vs. 40.6 +/- 12.7 mmHg; after 2 h, 41.5 +/- 10.7 vs. 46.3 +/- 15.2 mmHg; for C1 INH and cont rol animals, respectively). However, the RV could be loaded with a signific antly higher volume after both 1 h (60.0 +/- 20.0 ml (C1 INH) vs. 46.7 +/- 13.7 ml (control) balloon volume, P < 0.05), and 2 h of reperfusion (70.0 /- 8.9 ml vs. 60.0 +/- 6.3 ml; C1 INH and control animals, respectively; P < 0.05). Conclusions: Intracoronary administration of a C1 INH significantl y improves right ventricular function in an experimental transplant model. Thus, inhibition of the classic complement cascade may be a promising thera peutic approach for effective protection of myocardium from reperfusion inj ury after transplantation. (C) 2000 Published by Elsevier Science B.V.