Optimizing probucol administration to preserve left ventricular compliance after reperfusion injury in the heterotopic rat heart isograft.
BACKGROUND
We investigated the optimal method of administering probucol to attenuate reperfusion-induced diastolic abnormalities in the left ventricle of the heterotopically transplanted rat heart isograft.


METHODS
We assigned Lewis rats (n = 84) to 7 transplant groups. We arrested 42 hearts using coronary perfusion with hypothermic University of Wisconsin (UW) solution at 60 mm Hg and abdominally isografted the hearts. Neither donors nor recipients in the control group (C-C, n = 6) received probucol. Oral probucol (1% by weight in chow) was fed for 1 month before surgery to the donors only (OP-C, n = 6), the recipients only (C-OP, n = 6), or both (OP-OP, n = 6). We administered an intraperitoneal injection of probucol (300 mg/kg) in 3 ml oil 1 hour before surgery to the donors only (IP-C, n = 6), the recipients only (C-IP, n = 6), or both (IP-IP, n = 6). Transplanted hearts were reperfused for 15 minutes and re-arrested. We also arrested the control recipients' native hearts (native, n = 6). We measured post-mortem left ventricular compliance curves and myocardial water content.


RESULTS
The most compliant grafts were in Groups IP-IP, OP-OP, and C-IP. All isograft groups had significantly less left ventricular compliance than did native hearts. Myocardial water content was significantly greater in controls than in natives, OP-OP, and OP-C.


CONCLUSIONS
Pre-treatment with intraperitoneal probucol in cardiac isograft recipients combines optimal protection with simple administration when UW solution is used for both arrest and preservation. Further studies of the protective effect of probucol against reperfusion injury in large-animal models are warranted and should use intraperitoneal or intravenous injection in recipients.
Rabkin
David G
DG
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Weinberg
Alan D
AD
Spotnitz
Henry M
HM
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D016027:Heart Transplantation; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011292:Premedication; D011341:Probucol / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic; D016277:Ventricular Function, Left / Q000187:drug effects*
D000975:Antioxidants; D011341:Probucol