title: Pulmonary hypertension and reduced cardiac output during inhibition of nitric oxide synthesis in human septic shock.
abstract: It has been suggested that inhibitors of nitric oxide synthesis are of value in the treatment of hypotension during sepsis. In this pilot study, we examined the effects of inhibition of nitric oxide synthesis by continuous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME) at 1.5 mg/kg/h in a patient with severe septic shock. L-NAME produced a rise in mean arterial blood pressure and systemic vascular resistance; catecholamine infusion could be reduced. Parallel to these findings, there was a 50% reduction in cardiac output and a 5-fold rise in pulmonary vascular resistance, which resulted in severe pulmonary hypertension after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following the termination of L-NAME infusion, pulmonary artery pressure and blood pressure returned to baseline values, although pulmonary and systemic vascular resistance remained elevated for several hours. We conclude that nitric oxide appears to play a role in the cardiovascular derangements during human sepsis. Inhibition of nitric oxide synthesis with L-NAME can increase blood pressure and systemic vascular resistance. However, reduced cardiac output and pulmonary hypertension are possible side effects of continuous NO synthase inhibition. These side effects necessitate careful monitoring and may hinder the clinical application of NO synthase inhibitors.
authors.affiliation: Department of Surgery, University Hospital Rotterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Avontuur
authors.forename: M
authors.initials: M
authors.lastname: Biewenga
authors.forename: S L
authors.initials: SL
authors.lastname: Buijk
authors.forename: K J
authors.initials: KJ
authors.lastname: Kanhai
authors.forename: H A
authors.initials: HA
authors.lastname: Bruining
mesh_terms: D000368:Aged; D002302:Cardiac Output; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D010865:Pilot Projects; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester