Effects of N-Acetyl-L-Cysteine on Regional Blood Flow during Endotoxic Shock

Abstract

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 PvO₂ 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 group at the end of the study. We conclude that NAC can increase blood flow in the mesenteric, renal and femoral beds in endotoxic shock and this may be associated with a higher oxygen availability in the tissues.

Influence of N-acetylcysteine treatment on endotoxin-induced microcirculatory disturbances

“…Although we only investigated blood flow in a single postcapillary venule, our results suggest that NAC has beneficial effects on tissue perfusion during endotoxemia. Similar results were reported by other authors [13,14]. The way in which NAC augments tissue perfusion during endotoxemia or sepsis is still unclear.…”

“…Further measurements were conducted at 60, 90, and 120 min. The dosage of NAC was determined from the studies of other authors investigating the beneficial effects of NAC during endotoxemia or sepsis [13,14]. After the end of the observation period, the animal was sacrificed with an overdose of pentobarbital.…”

Pathophysiology of contrast-induced nephropathy

“…1). The renal protective effects of NAC may also be contributed to its vasodilatation properties evident by higher renal blood flow in dogs during endotoxin-induced shock with NAC infusion than those without [66]. NAC-infused animals also had higher GFR at 1 day and 7 days after induction of ischemia in addition to improved histological appearances of the kidneys 7 days after reperfusion compared with the control ones, although the mechanism by which NAC ameliorated the loss of renal function was unknown [67].…”

N-Acetylcysteine in the Prevention of Radiocontrast-Induced Nephropathy: Clinical Trials and End Points

“…The findings of Heyman et al [34] in rats suggest that NAC-related protective properties during the evolution of acute renal failure may be mediated in part by dilation of the constricted renal vasculature. Previous studies already have described vasodilatory properties of NAC [34,35].…”