Nitric oxide synthase inhibition reduces venous return in porcine
endotoxemia.
Saetre, Torunn, Otto A. Smiseth, Tim Scholz, Hege Carlsen, Lars
Nordsletten, Elisabeth Fahlstr[stod]om, Ansgar O. Aasen.
Institute for Surgical Research and Surgical Department B, The
National Hospital, N-0027 Oslo, Norway
APStracts 3:0147H, 1996.
Mechanisms of circulatory effects induced by nitric oxide synthase
inhibition in endotoxemia were investigated in thirty- six pigs
randomized to: 1) Endotoxin infusion (1.7 [mu]g/kg/hr iv) for 7 hrs
and bolus N-nitro-L-arginine methyl ester (L-NAME) 25 mg/kg iv after
3 hrs; 2) Endotoxin infusion for 7 hrs; 3) Saline infusion for 7 hrs
and L-NAME after 3 hrs; 4) Saline infusion for 7 hrs. Results:
Fifteen min. after L-NAME injection during endotoxemia, reductions in
cardiac output (41%, p< 0.05), portal venous flow (51%, p<
0.05), and hepatic artery flow (50%, p< 0.05) were observed. SVR
increased by 82%, p< 0.05 and the portocaval (PCR) vascular
resistance by 101 %, p< 0.05. Despite marked vasoconstriction
after L-NAME, left ventricular intracavitary filling pressure,
central venous pressure and arterial pressure remained unchanged.
During endotoxemia, hematocrit increased from 38.4 +/- 1.4 to 41.9
+/- 1.2 after L-NAME, and blood volume (n=3) was reduced by an
average of 8.3 ml / kg BW. These changes probably reflect
transcapillary fluid loss as urine output was unchanged. In
conclusion, L-NAME decreased intravascular blood volume and increased
splanchnic venous resistance. These effects will tend to reduce
venous return. Combined with a marked increase in left ventricular
afterload, L-NAME may thus compromise cardiovascular function in
endotoxemia.
Received 14 December 1995; accepted in final form 2 April 1996.
APS Manuscript Number H1170-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96