Attenuation of reperfusion injury with probucol in the heterotopic rat cardiac isograft

Background: We tested the hypothesis that pretreatment with the antioxidant probucol attenuates reperfusion-induced diastolic abnormalities in the het erotopic rat cardiac isograft. Methods: American Cancer Institute rats (n = 48) were divided into 6 groups . Hearts were arrested by coronary perfusion with 3 ml 4 degrees C Universi ty of Wisconsin solution at 60 mmHg. Eighteen donor hearts were divided int o 3 groups of 6 and arrested either 1 hour after intraperitoneal injection of 3 mi oil with (Prob Tx) or without (Oil Tx) probucol (300 mg/kg) or with out injection (Ctrl Tx). After a 90 minute storage period, abdominal isogra fting was performed with a total ischemic time of 2 hours. Following 15 min utes of blood reperfusion, donor hearts were rearrested and excised. Recipi ents' native hearts (NH, n = 18) were also arrested. Two additional groups with (Prob NR, n = 6) and without (Ctrl NR, n = 6) probucol pretreatment we re arrested and subjected to 2 hours of ischemia without reperfusion. Postm ortem LV pressure-volume curves and myocardial water content (MWC) were mea sured. Results: At each pressure interval normalized LV volume (LW) was significan tly greater for Prob Tx than Oil Tx or Ctrl Tx. Al isograft groups had sign ificantly lower LW at all pressure intervals and higher MWC than non-transp lanted hearts. Conclusions: Pretreatment with probucol attenuates reperfusion-induced decr eases in LVV in the heterotopic rat heart isograft model. Probucol, which i s orally active in humans, merits further study for its potential to improv e myocardial protection during cardiac surgery.