lodoxamide-tromethamine and Ischemia

Intravascular complement activation with either zymosan or cobra venom factor (CVF) impairs hepatic blood flow. Oxygen radical scavengers given at the time of complement activation attenuate the resulting hepatic ischemia. It is not clear whether complement-stimulated phagocytes or transiently ischemic then reperfused endothelial and parenchymal cells generated the toxic oxygen radicals. In this study, a group of rats were given allopurinol (50 mg/kg/day postoperatively X 3 days plus 100 mg/kg iv at t = 0), a specific inhibitor of xanthine oxidase, prior to complement activation with CVF (20 units/kg iv at t = 30 and 60 min) to determine whether xanthine oxidase-derived oxygen radicals contributed significantly to the hepatic perfusion abnormalities. Additional rats received lodoxamide tromethamine (10 mg/kg iv bolus at t = 0 followed by 20 mg/kg/hr iv infusion), a novel and potent inhibitor of mast cell release and inhibitor of xanthine oxidase, prior to the same CVF challenge to determine whether mast cell mediators were involved in the flow disturbance. Thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, and effective hepatic blood flow (EHBF) by galactose clearance were determined at t = 2 hr. The percentage change in total hemolytic complement activity (% delta CH50) was determined between serum obtained prior to sacrifice and at t = 0. Systemic hemodynamics and HCT were for the most part unaffected regardless of pretreatment group or challenge with CVF or saline. CVF challenge produced a 25% reduction (P less than 0.05) in EHBF in vehicle-pretreated rats compared to saline challenge. Neither allopurinol nor lodoxamide tromethamine significantly improved EHBF when given prior to CVF challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allopurinol; Amino Acids; Animals; Complement Activation; Complement System Proteins; Elapid Venoms; Hemodynamics; Ischemia; Liver Circulation; Nitriles; Oxamic Acid; Tromethamine

The antioxidant lodoxamide tromethamine was assessed for effects on experimental spinal cord ischemia in the rabbit. Lodoxamide (20 mg/kg/hr) or 0.9% sodium chloride was infused beginning 15 minutes before infrarenal aortic occlusion and continuing for 105 minutes. With an occlusion time of 20 minutes, eight of eight lodoxamide-treated animals and five of eight saline-treated animals regained function after reperfusion. However, by 48 hours after occlusion, seven of eight saline-treated animals were completely paralyzed, whereas only two of eight lodoxamide-treated animals were paralyzed. An ischemia time of 30 minutes exceeded the protective capacity of this treatment. These results suggest lodoxamide may be useful in alleviating ischemic damage to the spinal cord.

Topics: Amino Acids; Animals; Antioxidants; Aorta, Abdominal; Constriction; Ischemia; Male; Nitriles; Oxamic Acid; Paraplegia; Rabbits; Spinal Cord; Tromethamine