Nitric oxide synthase inhibition partially prevents decreased left
ventricular contractility during endotoxemia.
Herbertson, Michael J., Heinrich A. Werner, Keith R. Walley.
Pulmonary Research Laboratory, St. Paul's Hospital, University of
British Columbia, Vancouver, Canada, V6Z 1Y6
APStracts 2:0518H, 1995.
Decreased contractility of myocytes after cytokine exposure can be
prevented by nitric oxide synthase inhibition. Whether this is true
in an intact animal model of sepsis is unknown. Anesthetized pigs
were pretreated with saline or a nitric oxide synthase inhibitor, Nw
-Nitro-L-arginine, and then treated with saline or endotoxin. We
measured hemodynamics and left ventricular pressures (Millar
catheter) and volumes (conductance catheter). Left ventricular
contractility was assessed using the slope, Emax, of the end-systolic
pressure-volume relationship. Four hours after endotoxin infusion
Emax had decreased by 44 +/- 5% (p < 0.05) and mean arterial
pressure had decreased by 30 +/- 10% (p < 0.05). Pretreatment
with Nw-Nitro-L-arginine significantly reduced the decrease in Emax
to 28 +/- 3% (p < 0.05) and prevented the decrease in mean
arterial pressure. However, it also raised pulmonary artery pressure.
We conclude that nitric oxide contributes to the early decrease in
left ventricular contractility after endotoxin in the intact animal.
However, the vascular effects of nitric oxide synthase inhibition
increase right and left ventricular afterloads which were detrimental
to cardiac function.
Received 23 December 1994; accepted in final form 7 November
1995.
APS Manuscript Number H1128-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95