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 at 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.