Cardioprotective effects of Lazaroid U-74389G on ischemia-reperfusion injury in canine hearts.
BACKGROUND
Lazaroid, an inhibitor of iron-mediated lipid peroxidation, has been shown to reduce free radical-mediated injury after ischemia and reperfusion. The effect of Lazaroid U-74389G was investigated on ischemia-reperfusion injury of the heart through preservation and transplantation (Tx) in dogs.


METHODS
Eleven pairs of adult mongrel dogs weighing 8.5 to 12 kg formed the recipient-donor combinations. Following electromechanical arrest of the heart using cardioplegia, the coronary vascular beds were washed out with a cold University of Wisconsin solution followed by 12-hour preservation and orthotopic Tx. Experimental animals were divided into 2 groups; 6 pairs formed the control group, and 5 formed the Lazaroid-treated group in which Lazaroid U-74389G at 10 mg/kg was administered intravenously 30 minutes before reperfusion of the heart. The cardiac function including cardiac output, left ventricular (LV) pressure, and LV dp/dt was assessed 2 hours after Tx by comparing it with the recovery rates (%) from cardiac function of donor dogs. Each transplanted heart was harvested for histological study.


RESULTS
The recovery of cardiac function after Tx was significantly better in the Lazaroid-treated group than in the control group. Histologically, myocardial damage, evaluated by both light and transmission electron microscopy, was less evident in the Lazaroid-treated group than in the control group.


CONCLUSIONS
Early cardiac function following Tx was significantly better and histological damage was less in the Lazaroid-treated group than in the control group, suggesting that Lazaroid U-74389G is effective in preventing ischemia-reperfusion injury after preservation and Tx.
Takahashi
T
T
Second Department of Surgery, Gunma University School of Medicine, Japan.
Takeyoshi
I
I
Hasegawa
Y
Y
Koyano
T
T
Yamagishi
T
T
Oshima
K
K
Matsumoto
K
K
Morishita
Y
Y
D000241:Adenosine / Q000627:therapeutic use; D000493:Allopurinol / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000627:therapeutic use; D004285:Dogs; D005609:Free Radicals / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D016027:Heart Transplantation; D007275:Injections, Intravenous; D007328:Insulin / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000097:blood; D008854:Microscopy, Electron; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000648:ultrastructure; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000627:therapeutic use; D011281:Pregnatrienes / Q000008:administration & dosage / Q000627:therapeutic use*; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011887:Raffinose / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000975:Antioxidants; D002314:Cardioplegic Solutions; D005609:Free Radicals; D007328:Insulin; D008054:Lipid Peroxides; D019188:Organ Preservation Solutions; D011281:Pregnatrienes; D020011:Protective Agents; C055206:University of Wisconsin-lactobionate solution; C074965:U 74389F; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose