Table 1 Non-clinical and clinical trials investigating the effects of nitric oxide synthase inhibitors or nitric oxide donors during endotoxemia/sepsis
From: Differentiated control of deranged nitric oxide metabolism: a therapeutic option in sepsis?
Design | Intervention (NOS inhibitor or NO donor) | Effect |
|---|---|---|
Non-clinical trials | Â | Â |
Pseudomonas aeruginosa instilled into airways of sheep after inhalation of cotton smoke [18] | BBS-2 (highly selective iNOS inhibitor) | Pulmonary gas exchange improved and airway obstruction was partially reduced. |
Intravenous infusion of P. aeruginosa in pigs [19] | Combined L-NIL (selective iNOS inhibitor) and Tempol (superoxide scavenger) | Promoted protection against cardiovascular, hepatosplanchnic metabolic, renal, and coagulation abnormalities |
Intravenous infusion of P. aeruginosa in pigs [20] | L-NIL (selective iNOS inhibitor) | Protective effect on, for example, ileal mucosal microcirculation |
LPS-induced endotoxemia in rats [26] | Sodium nitroprusside (NO donor) | Inhibition of increase of non-perfused sinusoids |
LPS-induced endotoxic shock in dogs [27] | SIN-1 (NO donor) | Low and moderate doses increased mesenteric blood flow. |
Clinical trials | Â | Â |
Humans with septic shock [21] | 546C88 (non-selective NOS inhibitor) | Increased mortality |
Patients with septic shock [28] | Nitroglycerin (NO donor) | Temporary decrease of MAP and central venous pressure but also strong increase in microvascular flow after 2 minutes |
Patients with severe sepsis [29] | Nitroglycerin (NO donor) | No improvement of the microcirculation compared with control group after 24 hours; higher mortality in the nitroglycerin group |