TESTOSTERONE RECEPTOR BLOCKADE AFTER TRAUMA-HEMORRHAGE IMPROVES CARDIAC AND HEPATIC FUNCTIONS IN MALES

Although studies have shown that testosterone receptor blockade with f lutamide after hemorrhage restores the depressed immune function, it r emains unknown whether administration of flutamide following trauma an d hemorrhage and resuscitation has any salutary effects on the depress ed cardiovascular and hepatocellular functions. To study this, male ra ts underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the ani mals could not maintain this pressure. Ringer lactate was given to mai ntain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitate d with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle pr opanediol was injected subcutaneously 15 min before the end of resusci tation. Various in vivo heart performance parameters (e.g., maximal ra te of the pressure increase or decrease), cardiac output, and hepatoce llular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resusci tation. Additionally, hepatic microvascular blood flow (HMBF) was dete rmined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular fun ction decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone rece ptor blocker flutamide, however, significantly improved cardiac perfor mance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocel lular functions in males following trauma and hemorrhagic shock.