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.
OBJECTIVE
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.


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).


CONCLUSIONS
l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h.
Dzavík
Vladimir
V
University Health Network, Toronto General Hospital, 6-246, 200 Elizabeth Street, Toronto M5G 2C4, Ontario, Canada. vlad.dzavik@uhn.on.ca
Cotter
Gad
G
Reynolds
Harmony R
HR
Alexander
John H
JH
Ramanathan
Krishnan
K
Stebbins
Amanda L
AL
Hathaway
David
D
Farkouh
Michael E
ME
Ohman
E Magnus
EM
Baran
David A
DA
Prondzinsky
Roland
R
Panza
Julio A
JA
Cantor
Warren J
WJ
Vered
Zvi
Z
Buller
Christopher E
CE
Kleiman
Neal S
NS
Webb
John G
JG
Holmes
David R
DR
Parrillo
Joseph E
JE
Hazen
Stanley L
SL
Gross
Steven S
SS
Harrington
Robert A
RA
Hochman
Judith S
JS
D000368:Aged; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012770:Shock, Cardiogenic / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase