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 heterotopic 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 University of Wisconsin solution at 60 mmHg. Eighteen donor hearts were divided into 3 groups of 6 and arrested either 1 hour after intraperitoneal injection of 3 ml oil with (Prob Tx) or without (Oil Tx) probucol (300 mg/kg) or without injection (Ctrl Tx). After a 90 minute storage period, abdominal isografting was performed with a total ischemic time of 2 hours. Following 15 minutes of blood reperfusion, donor hearts were rearrested and excised. Recipients' native hearts (NH, n = 18) were also arrested. Two additional groups with (Prob NR, n = 6) and without (Ctrl NR, n = 6) probucol pretreatment were arrested and subjected to 2 hours of ischemia without reperfusion. Postmortem LV pressure-volume curves and myocardial water content (MWC) were measured.


RESULTS
At each pressure interval normalized LV volume (LVV) was significantly greater for Prob Tx than Oil Tx or Ctrl Tx. All isograft groups had significantly lower LVV at all pressure intervals and higher MWC than non-transplanted hearts.


CONCLUSIONS
Pretreatment with probucol attenuates reperfusion-induced decreases in LVV in the heterotopic rat heart isograft model. Probucol, which is orally active in humans, merits further study for its potential to improve myocardial protection during cardiac surgery.
Rabkin
D G
DG
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Jia
C X
CX
Spotnitz
H M
HM
D000005:Abdomen; D000241:Adenosine / Q000633:toxicity; D000493:Allopurinol / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001834:Body Water / Q000378:metabolism; D002306:Cardiac Volume; D005978:Glutathione / Q000633:toxicity; D016027:Heart Transplantation; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000633:toxicity; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D019188:Organ Preservation Solutions; D009929:Organ Size; D011341:Probucol / Q000008:administration & dosage / Q000627:therapeutic use*; D011887:Raffinose / Q000633:toxicity; D051381:Rats; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017725:Ventricular Pressure
D000975:Antioxidants; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D011341:Probucol