Sodium–hydrogen inhibitor cariporide (HOE 642) improves in situ protection of hearts from non–heart-beating donors

Reperfusion injury is a vital problem in non–heart-beating donor (NHBD) organs. The sodium–hydrogen inhibitor cariporide is thought to improve cellular integrity after ischemia and reperfusion. Recently, we demonstrated the possibility of preserving hearts with in situ perfusion after circulatory death. The purpose of this study was to determine whether cariporide improves in situ heart protection. We studied 20 pigs (18 ± 2 kg). Hearts in the conventional group (CON, n = 6) underwent cardioplegic arrest with University of Wisconsin solution and then were explanted and stored for 150 minutes on ice. In the other groups, a catheter was placed in each ascending aorta and right atrium. After disconnecting the ventilator, hypoxia caused circulatory arrest within 7 ± 2 minutes. The aorta was endoclamped, and continuous in situ perfusion of the aortic root was maintained for 60 minutes with University of Wisconsin solution (UW, n = 7) or with UW solution and cariporide (CAR, n = 7). After explantation, the hearts were stored on ice for 90 minutes. In all groups, hearts were reperfused with homologous, whole pig blood in an isolated working heart model for 45 minutes. We monitored stroke-work index on-line, intermittently measured troponin I and malondialdehyde, and compared light microscopic examinations among the groups. Stroke-work index was higher in the CAR group compared with the UW group during the last 20 minutes of reperfusion (10 3dynes × cm × beats -1× gm -1, 6.6 ± 1.4 vs 4.5 ± 2.0, p < 0.05), troponin I was lower in the CAR group compared with the UW group (161 ± 32 ng/ml vs 277 ± 35 ng/ml, p < 0.05). Results of malondialdehyde and light microscopic examinations were slightly better in the CAR group, without reaching statistical significance. Cariporide as an additive to UW solution improves functional recovery and decreases myocardial damage in hearts from NHBDs protected with an in situ perfusion technique.