Studies of ischemia-reperfusion injury in skeletal muscle: Efficacy of 21-aminosteroids on microcirculation and muscle contraction after an extended period of warm ischemia

The present study was conducted to elucidate the effects of tirilazad mesylate (U-74006F), a potent inhibitor of lipid peroxidation, on vessel diameter, capillary perfusion, and contractile function of rat cremaster muscle during a 90-minute reperfusion period that followed 4 hours of warm ischemia. Two groups of 32 animals were treated with either 3 mg/kg U-74006F or the vehicle (citrate buffer) alone 30 minutes before ischemia, 90 minutes after ischemia, and immediately before reperfusion. With use of intravital videomicroscopy, the internal luminal diameters of preselected vessels were measured prior to ischemia and during reperfusion. The area that filled with fluorescein was determined at 15-minute intervals for as long as 90 minutes of reperfusion, and contractile function was examined in vitro in an organ bath Lit that point In the U-74006F group, after 90 minutes of reperfusion the vessel diameters returned completely to baseline and the diameters of all three categories of vessels at every time point from 10 to 90 minutes of reperfusion had significantly more rapid recovery than the controls. Although some evidence of more rapid fluorescence was noted in the U-74006F group, the: two groups did not differ significantly at any time period of reperfusion. In response to tetanic stimulation. the muscles treated with U-74006F had a significantly greater contractile force at all stimulation frequencies than the control muscles. Our findings indicate that pretreatment with U-74006F can effectively decrease the rise of vascular resistance and preserve the contractile function of skeletal muscle during early reperfusion, thereby attenuating ischemia-reperfusion injury.