Abstract
Objective: Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathophysiology of septic shock. This study was designed to see whether S-methylisothiourea sulfate (SMT), a selective inhibitor for iNOS, prevents cardiovascular changes and multiple organ damage in the canine endotoxic shock model.¶Design: Prospective, comparable, experimental study.¶Setting: Laboratory at a university hospital.¶Subjects: Twenty male mongrel dogs were studied under pentobarbital anesthesia.¶Interventions: Dogs were divided into three groups: bacterial lipopolysaccharide (LPS) group (n = 7) receiving continuous infusion of LPS (2 mg/kg/h for 1 h); LPS plus SMT group (n = 7) receiving LPS and SMT (1 mg/kg, bolus i. v., followed by continuous infusion of 1 mg/kg/h for 1 h); and vehicle plus SMT group (n = 6).¶Measurements and results: Hemodynamics, blood gas parameters, and urine output were measured during 6 h observation periods. Serum levels of lactate, transaminases, and bilirubin were measured at baseline, 1 and 6 h. Creatinine and free water clearance, urine sodium excretion and fractional excretion of sodium were calculated. LPS caused a profound hypotension associated with decreases in cardiac output and oxygen delivery, lactic acidosis, renal and liver dysfunction, and thrombocytopenia. SMT prevented the LPS-induced hypotension and renal dysfunction, whereas it did not affect the LPS-induced decreases in cardiac output or oxygen delivery, hyperlactatemia, liver dysfunction, or thrombocytopenia. SMT alone had no appreciable effects on hemodynamics, blood gases, liver or renal functions.¶Conclusions: These findings show that SMT improves renal, but not hepatic dysfunction, in dogs with endotoxic shock, suggesting that iNOS-derived NO plays differential roles in sepsis-associated multiple organ dysfunction.
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Received: 16 May 1999 Final revision received: 13 September 1999 Accepted: 15 November 1999
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Mitaka, C., Hirata, Y., Masaki, Y. et al. S-Methylisothiourea sulfate improves renal, but not hepatic dysfunction in canine endotoxic shock model. Intensive Care Med 26, 117–124 (2000). https://doi.org/10.1007/s001340050023
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DOI: https://doi.org/10.1007/s001340050023