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Aminoethyl-isothiourea, a nitric oxide synthase inhibitor and oxygen radical scavenger, improves survival and counteracts hemodynamic deterioration in a porcine model of streptococcal shock
- Source :
- Critical Care Medicine. 28:2697-2706
- Publication Year :
- 2000
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2000.
-
Abstract
- To test the effect of a continuous infusion of the nitric oxide (NO) synthase (S) inhibitor aminoethyl-isothiourea (AE-ITU) on survival time, hemodynamics, and oxygen transport in a porcine model of live group A streptococcal (GAS) sepsis. Furthermore, to examine the role of endothelin-1, histamine, and reactive oxygen species (ROS) in streptococcal shock.Prospective, randomized trial.Laboratory at a university hospital.Twenty-eight pigs with an average weight of 25 kg.Sixteen animals received a continuous infusion of live Streptococcus pyogenes 1.3 x 10(10) colony forming units/hr: eight received fluids only, and the other eight received an intravenous infusion of AE-ITU 10 mg/kg/hr starting 30 mins before the GAS challenge. Six control pigs received AE-ITU 10 mg/kg/hr iv for 5 hrs. Another six animals received half the dose of GAS over 5 hrs.GAS infusion caused a rapid increase in pulmonary, hepatic, and systemic vascular resistance, followed by hypotension with a 90% lethality at 4 hrs. Treatment with AE-ITU increased 4-hr survival in septic animals from 1/8 to 8/8 and 5-hr survival from 0/8 to 5/8, prevented hypotension, and increased urine output. AE-ITU attenuated the decrease in cardiac output, liver blood flow, and oxygen delivery, and hepatic arterial blood flow as a fraction of cardiac output increased (all p.05). Plasma nitrate/nitrite levels decreased in all animals. Inducible NOS and endothelial constitutive NOS activities in liver, gut, and lung were not increased during sepsis, nor were they decreased after AE-ITU. Plasma levels of endothelin-1 and methylhistamine increased in all septic animals and were not modified by AE-ITU. AE-ITU prevented the increase in monocyte ROS production caused by GAS. In control animals, AE-ITU caused an increase in mean arterial pressure, liver blood flow, and oxygen delivery.In this model of porcine GAS-induced septic shock, which was not associated with enhanced NO production, infusion of the NOS inhibitor AE-ITU prolonged survival, prevented hypotension, and improved cardiac contractility, organ perfusion, and tissue oxygenation. These beneficial effects of AE-ITU might be a result of the combined effect of ROS scavenging and modulation of local NO production, thus improving the balance of vasodilator and vasoconstrictor forces and reducing oxidative stress.
- Subjects :
- Male
Streptococcus pyogenes
Swine
Radical
Pharmacology
Nitric Oxide
Critical Care and Intensive Care Medicine
medicine.disease_cause
Nitric oxide
Sepsis
Random Allocation
chemistry.chemical_compound
Streptococcal Infections
Animals
Medicine
biology
business.industry
Hemodynamics
Thiourea
Oxygen transport
medicine.disease
Shock, Septic
Survival Rate
Nitric oxide synthase
Disease Models, Animal
Biochemistry
chemistry
Enzyme inhibitor
Shock (circulatory)
biology.protein
Female
medicine.symptom
business
Isothiuronium
Subjects
Details
- ISSN :
- 00903493
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....098e65824446971269c8e2575c62fcf7