Effects of s-isopropyl-isothiourea, a potent inhibitor of
endothelial nitric oxide synthase, in rodent and porcine hemorrhagic
shock.
Vromen, Amos, Csaba Szab[acute]o, Garry J. Southan, and Andrew L.
Salzman.
Children's Hospital Medical Center, Divisions of Critical Care and
Pediatric Surgery, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA,
Tel.: (513) 559-4855, Fax: (513) 559-4267
APStracts 3:0158A, 1996.
We characterized the response to intravenous S-isopropyl-isothiourea
(IPTU), a novel potent NOS inhibitor, in rodent and porcine models of
hemorrhagic shock (HS). IPTU (at 300 [mu]g/kg, administered as 3
subsequent bolus injections), in anesthetized rats hemorrhaged to a
mean arterial blood pressure (MAP) of 35 mmHg, increased MAP and
improved survival over 120 min. In anesthetized pigs hemorrhaged to a
MAP of 45 mmHg, IPTU (0.3 mg/kg plus 1g/kg/h) increased MAP and
systemic vascular resistance. IPTU did not alter the cardiac index,
renal blood flow, arterial and portal oxygen content, splanchnic
oxygen consumption or extraction. In contrast, infusion of
norepinephrine (100 [mu]g/kg/h) did not alter MAP and increased
mortality in the rat model, whereas it caused a transient increase in
MAP and a tachycardia in the porcine model of HS, without
significantly affecting the other parameters studied. Inhibition of
the endothelial NOS in early, severe HS may have beneficial effects
on blood pressure and survival, without improving cardiac output and
splanchnic and renal perfusion.
Received 5 December 1995; accepted in final form 7 March 1996.
APS Manuscript Number A1259-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96