Effect of lazaroid U-74389G on pulmonary ischemia-reperfusion injury in dogs.

Lipid peroxidation induced by oxygen free radicals is a contributing factor in ischemia-reperfusion injury. Lazaroid U-74389G (LAZ-G) is a group of new synthetic 21-aminosteroids and inhibits irondependent lipid peroxidation. We investigated the effects of LAZ-G on pulmonary ischemia-reperfusion injury in dogs. Twenty dogs were divided into three groups. In the LAZ-G group (n = 6), LAZ-G was administered 15 min before ischemia. In the St group (n = 5), methylprednisolone was injected 15 min before ischemia and 15 min before reperfusion. In the control group (n = 9), the vehicle of Lazaroid was injected 15 min before ischemia. Warm ischemia was induced for 3 h by clamping the pulmonary artery and veins. Arterial oxygen saturation (SaO2), cardiac output (CO), left pulmonary vascular resistance (L-PVR), and blood levels of interleukin-1beta mRNA were measured. The lung specimen was harvested for histologic study and polymorphonuclear neutrophils (PMNs) counting. SaO2 levels at 30 min and 2 h after reperfusion were significantly higher in the LAZ-G group than in the control group. After 30 min of reperfusion, CO was significantly better in the LAZ-G group than in the St and control groups, and the L-PVR level was significantly lower in the LAZ-G group than in the control group. Survival rates were significantly better in the LAZ-G group than in the control group. Histological damages and PMNs infiltration were more severe in the control group than in the LAZ-G group. Interleukin-1beta mRNA levels were lower in the LAZ-G group than in the control group. Lazaroid U-74389G appears to generate a protective effect against ischemia-reperfusion injury of the lung.