Literature DB >> 17459901

Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction: a phase II dose-ranging study.

Vladimir Dzavík1, Gad Cotter, Harmony R Reynolds, John H Alexander, Krishnan Ramanathan, Amanda L Stebbins, David Hathaway, Michael E Farkouh, E Magnus Ohman, David A Baran, Roland Prondzinsky, Julio A Panza, Warren J Cantor, Zvi Vered, Christopher E Buller, Neal S Kleiman, John G Webb, David R Holmes, Joseph E Parrillo, Stanley L Hazen, Steven S Gross, Robert A Harrington, Judith S Hochman.   

Abstract

AIMS: Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery. METHODS AND
RESULTS: Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS).
CONCLUSION: l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h.

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Year:  2007        PMID: 17459901     DOI: 10.1093/eurheartj/ehm075

Source DB:  PubMed          Journal:  Eur Heart J        ISSN: 0195-668X            Impact factor:   29.983


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