Haematological, physiological and survival data in a porcine model of adult respiratory distress syndrome induced by endotoxaemia. Effects of treatment with N-acetylcysteine.
The effects of N-acetylcysteine (NAC)--which is supposed to act as a free radical scavenger--were evaluated on lung function, haemodynamics and oxygen transport in a porcine model of pulmonary and cardiovascular failure induced by endotoxaemia. Three pigs, serving as controls, received NAC without endotoxin (E) for 6 h, and no notable physiological changes were found. Five pigs received a continuous infusion of E alone for 6 h and displayed a 90% decrease in leukocyte count and a 66% decrease in platelet count. Physiologically a four-fold increase in venous admixture (Qva/Qt), a nearly 2-3 fold increase in mean pulmonary arterial pressure (MPAP) and a progressive decline in cardiac output (Qt) of 60% were documented. Extravascular lung water (EVLW) increased 66%, mean arterial pressure (MAP) decreased 46% and oxygen delivery decreased 52%, leading to a metabolic acidosis. Three animals died during the observation period. Contrastingly, eight pigs, pretreated with NAC 150 mg.kg-1 which was continued at 20 mg.kg-1.h-1, showed a significantly attenuated response to E. Thus, leukocyte and platelet counts decreased 70% and 48%, respectively. Physiologically Qva/Qt increased 2.5-3 fold, MPAP increased 1.3-2 fold, and Qt decreased 32%. EVLW increased 27%, MAP decreased 27% and oxygen delivery decreased only 33% which kept the pH in the normal range. All animals survived the observation period, a significant difference from the E alone group. Thus, NAC significantly attenuated all monitored haematological and pathophysiological changes in the endotoxin model of ARDS in pigs. In addition to a reported free radical scavenger effect of NAC, our results support the assumption that NAC may counteract leukocyte and platelet aggregation in the lung thereby contributing to the beneficial outcome.
Modig
J
J
Department of Anaesthesiology, University Hospital of Uppsala, Sweden.
Sandin
R
R
D000111:Acetylcysteine / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000008:administration & dosage; D004926:Escherichia coli; D005260:Female; D006400:Hematocrit; D006801:Humans; D007231:Infant, Newborn; D007958:Leukocyte Count; D008297:Male; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D010976:Platelet Count; D012127:Respiratory Distress Syndrome, Newborn / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013552:Swine
D004731:Endotoxins; D000111:Acetylcysteine