EFFECTS OF N-ACETYL-L-CYSTEINE ON REGIONAL BLOOD-FLOW DURING ENDOTOXIC-SHOCK

We previously reported that N-acetyl-L-cysteine (NAC), an oxygen free radical scavenger, can incrase the oxygen extraction capabilities duri ng endotoxic shock when blood flow is progressively reduced. In the pr esent study, we investigated whether the protective effects of NAC are related to an improvement in regional blood flow following endotoxemi a. Fourteen anesthetized, saline-infused and ventilated dogs were divi ded into two groups: 7 dogs received NAC (150 mg/kg, followed by a 20 mg.kg . h infusion), and the other 7 dogs served as a control time-mat ching group. Thirty minutes later all the dogs received Escherichia co li endotoxin (2 mg/kg) i.v. A saline infusion was started 30 min after endotoxin challenge to restore pulmonary artery occlusion pressure to baseline and maintain it constant. Regional blood flow was measured b y ultrasonic volume flowmeter. In the control group, arterial pressure , left ventricular stroke work index and systemic vascular resistance remained lower than baseline. Mesenteric, renal and femoral arterial b lood flow increased but only femoral blood flow returned to baseline l evels. In the NAC group, cardiac index and left ventricular stroke wor k index remained higher and systemic and pulmonary vascular resistance were lower than in the control group. Blood flow in mesenteric, renal and especially femoral arteries was higher than in the control group. Fractional blood flow increased only in the femoral artery. PaO2 and PvO(2) had similar courses in the two groups. A higher venous admixtur e was associated with a higher cardiac index and a lower pulmonary vas cular resistance in the NAC group, Oxygen delivery and oxygen uptake w ere higher in the NAC-treated than in the control animals throughout t he study, Oxygen extraction ratio was higher in the NAC Oxygen extract ion group at the end of the study. We conclude that NAC can increase b lood Oxygen free radicals flow in the mesenteric, renal and femoral be ds in endotoxic shock and this may be associated with a higher oxygen availability in the tissues.