Cardiology 2008-01-01

Nitric oxide synthase inhibitor (MTR-105) during open-heart surgery. A pilot double-blind placebo-controlled study of hemodynamic effects and safety.

Lior Sasson, Andrei Ureche, Gheorghe Manolache, Anatol Ciubotaru, Jeffrey S Borer, Arie Schachner

Index: Cardiology 111(3) , 181-7, (2008)

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Abstract

Hypotension is common immediately following cardiopulmonary bypass. Experimentally, MTR-105 (S-ethylisothiuronium diethylphosphate), a fast-acting synthetic nitric oxide synthase inhibitor, rapidly increases blood pressure. The purpose of the current study was to assess the influence of MTR-105 on hemodynamics early after cardiopulmonary bypass in patients undergoing open-heart surgery.Thirty-six patients with an ejection fraction >50% undergoing open-heart surgery were randomly assigned to either 50 microg kg(-1) min(-1) MTR-105 (M50, n = 12), 10 microg kg(-1) min(-1) MTR-105 (M10, n = 12) or buffered phosphate solution (placebo control, n = 12). Half suffered from atrial fibrillation and 75% had severe tricuspid regurgitation. Patients received the drug for 6 h after cross-clamp removal. Hemodynamic variables were measured before drug administration until 24 h after operation. Adverse events were recorded from study drug initiation through 30 days after the operation.Compared with control, both MTR-105 doses were associated with an immediate increase in systemic blood pressure (16%) and systemic vascular resistance and a decrease in cardiac index. Half-life time of MTR-105 was calculated to be 4.1 +/- 0.8 h (M10) and 4.45 +/- 0.92 h (M50). Three patients died during hospitalization, unrelated to the study medication.At the doses employed, MTR-105 appears hemodynamically active in increasing both blood pressures.Copyright 2008 S. Karger AG, Basel.