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 ne w synthetic 21-aminosteroids and inhibits iron-dependent lipid peroxidation . We investigated the effects of LAZ-G on pulmonary ischemia-reperfusion in jury in dogs. Twenty dogs were divided into three groups. In the LAZ-G grou p (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 b efore reperfusion. In the control group (n = 9), the vehicle of Lazaroid wa s injected 15 min before ischemia. Warm ischemia was induced for 3 h by cla mping the pulmonary artery and veins. Arterial oxygen saturation (SaO(2)), cardiac output (CO), left pulmonary vascular resistance (L-PVR), and blood levels of interleukin-1 beta mRNA were measured. The lung specimen was harv ested for histologic study and polymorphonuclear neutrophils (PMNs) countin g. SaO(2) levels at 30 min and 2 h after reperfusion were significantly hig her in the LAZ-G group than in the control group. After 30 min of reperfusi on, CO was significantly better in the LAZ-G group than in the St and contr ol groups, and the L-PVR level was significantly lower in the LAZ-G group t han in the control group. Survival rates were significantly better in the L AZ-G group than in the control group. Histological damages and PMNs infiltr ation were more severe in the control group than in the LAZ-G group. Interl eukin-1 beta mRNA levels were lower in the LAZ-G group than in the control group. Lazaroid U-74389G appears to generate a protective effect against is chemia-reperfusion injury of the lung.