Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock

Amos Vromen, Csaba Szabo, Garry J. Southan, Andrew L. Salzman

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

We characterized the response to intravenous S-isopropyl isothiourea (IPTU), a novel potent nitric oxide synthase (NOS) inhibitor, in rodent and porcine models of hemorrhagic shock (HS). IPTU (at 300 μg/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 1 mg · kg-1 · h-1) increased MAP and systemic vascular resistance. IPTU did not alter the cardiac index, renal blood flow, arterial and portal oxygen content, or splanchnic oxygen consumption or extraction. In contrast, infusion of norepinephrine (100 μg · kg-1 · h-1) 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 altering cardiac output and splanchnic and renal perfusion.

Original languageEnglish (US)
Pages (from-to)707-715
Number of pages9
JournalJournal of Applied Physiology
Volume81
Issue number2
StatePublished - Aug 1996
Externally publishedYes

Fingerprint

Hemorrhagic Shock
Nitric Oxide Synthase
Arterial Pressure
Swine
Viscera
Nitric Oxide Synthase Type III
Renal Circulation
Tachycardia
Oxygen Consumption
Cardiac Output
Vascular Resistance
Rodentia
Norepinephrine
Perfusion

Keywords

  • cardiac output
  • constitutive endothelial nitric oxide synthase
  • contraction
  • perfusion
  • survival

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock. / Vromen, Amos; Szabo, Csaba; Southan, Garry J.; Salzman, Andrew L.

In: Journal of Applied Physiology, Vol. 81, No. 2, 08.1996, p. 707-715.

Research output: Contribution to journalArticle

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