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 during endotoxic shock when blood flow is progressively reduced. In the present study, we investigated whether the protective effects of NAC are related to an improvement in regional blood flow following endotoxemia. Fourteen anesthetized, saline-infused and ventilated dogs were divided 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-matching group. Thirty minutes later all the dogs received Escherichia coli 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 by 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 blood flow increased but only femoral blood flow returned to baseline levels. In the NAC group, cardiac index and left ventricular stroke work 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 admixture was associated with a higher cardiac index and a lower pulmonary vascular resistance in the NAC group, Oxygen delivery and oxygen uptake were higher in the NAC-treated than in the control animals throughout the study, Oxygen extraction ratio was higher in the NAC Oxygen extraction group at the end of the study. We conclude that NAC can increase blood Oxygen free radicals flow in the mesenteric, renal and femoral beds in endotoxic shock and this may be associated with a higher oxygen availability in the tissues.