Effects of selective nitric oxide synthase inhibitor in sheep with endotoxic shock

OBJECTIVE: To investigate the effects of S-methylisothiourea sulfate (SMT), a selective inducible nitric oxide synthase (iNOS) inhibitor, on hyperdynamic endotoxic shock sheep. METHODS: Endotoxic shock was induced by Escherichia coli endotoxin in both control (n = 8) and SMT groups (n = 8). SMT was given intravenously. Hemodynamic data, oxygen delivery derived parameters and intramucosal pH (pHi) were measured. RESULTS: The control group had a hyperdynamic state, similar to that of human septic shock. In the SMT group, blood pressure was maintained at baseline, and cardiac index (CI) was lower than that in the control group (P < 0.05). Oxygen extraction ratio (O2 ext) was increased up to 40% +/- 5% and was much higher than that of the control group (P < 0.01). Pulmonary artery pressure (PAP) was higher than that of the control group (P < 0.01), and pHi decreased gradually similarly to the control group. CONCLUSION: SMT restored the blood pressure and increased O2 extespecially in the gut, but decreased CI and oxygen delivery and increased PAP. So over inhibition of iNOS should be cautiously considered.