Attenuation of vascular endothelial dysfunction by testosterone receptor blockade after trauma and hemorrhagic shock

Hypothesis: The salutary effects of the testosterone receptor antagonist fl utamide on the depressed immune and cardiovascular functions after hemorrha ge and resuscitation are related to improved endothelial cell function, whi ch can subsequently lead to an increase in organ blood flow, oxygen deliver y, and tissue oxygen consumption. Design, Interventions, and Main Outcome Measures: Male adult rats underwent a 5-cm midline laparotomy (ie, trauma) and were bled to and maintained at a mean systemic arterial pressure of 40 mm Hg until 40% maximal blood-out v olume was returned in the form of Ringer lactate). The animals were then re suscitated with 4 times the total volume of shed blood with Ringer lactate for 60 minutes. Flutamide (25 mg/kg) or an equivalent volume of the vehicle propanediol was injected subcutaneously 15 minutes before the end of resus citation. At 20 hours after resuscitation, aortic rings (approximately 2.5 mm. in length) were isolated and mounted in an organ chamber. Dose response s for an endothelium-dependent vasodilator (acetylcholine chloride) and end othelium-independent vasodilator (nitroglycerine) were determined. Organ bl ood flow was measured using strontium 85-labeled microspheres. Total hemogl obin and oxygen content in the femoral artery and portal, hepatic, and rena l veins were determined. Oxygen delivery and consumption in liver, small in testine, and kidneys were calculated. Results: Administration of flutamide after traumahemorrhage attenuated the depressed endothelial function. Furthermore, flutamide treatment restored t he reduced blood flow and oxygen delivery and consumption in all organs tes ted after trauma-hemorrhage and resuscitation. Conclusion: Flutamide appears to be a useful adjunct for improving vascular endothelial function and regional hemodynamics after trauma-hemorrhage and resuscitation.