TY - JOUR
T1 - Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction
T2 - A phase II dose-ranging study
AU - Džavík, Vladimir
AU - Cotter, Gad
AU - Reynolds, Harmony R.
AU - Alexander, John H.
AU - Ramanathan, Krishnan
AU - Stebbins, Amanda L.
AU - Hathaway, David
AU - Farkouh, Michael E.
AU - Ohman, E. Magnus
AU - Baran, David A.
AU - Prondzinsky, Roland
AU - Panza, Julio A.
AU - Cantor, Warren J.
AU - Vered, Zvi
AU - Buller, Christopher E.
AU - Kleiman, Neal S.
AU - Webb, John G.
AU - Holmes, David R.
AU - Parrillo, Joseph E.
AU - Hazen, Stanley L.
AU - Gross, Steven S.
AU - Harrington, Robert A.
AU - Hochman, Judith S.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Acute myocardial infarction
KW - Cardiogenic shock
KW - Inflammation
KW - L-N-monomethyl-arginine (L-NMMA)
KW - Nitric oxide synthase
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U2 - 10.1093/eurheartj/ehm075
DO - 10.1093/eurheartj/ehm075
M3 - Article
C2 - 17459901
AN - SCOPUS:34548301578
SN - 0195-668X
VL - 28
SP - 1109
EP - 1116
JO - European heart journal
JF - European heart journal
IS - 9
ER -