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Nitric oxide synthase inhibitor (MTR-105) during open-heart surgery. A pilot double-blind placebo-controlled study of
Lior Sasson1, Andrei Ureche, Gheorghe Manolache
1Angela and Sami Shamoon Cardiothoracic Surgery Department, Edith Wolfson Medical Center, Holon, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
At the doses employed, MTR-105 appears hemodynamically active in increasing both blood pressures.
Insights
MTR-105, a nitric oxide synthase inhibitor, effectively increased blood pressure in patients after open-heart surgery. This study investigated its hemodynamic effects in patients undergoing cardiopulmonary bypass.
Area of Science:
- Cardiovascular Pharmacology
- Anesthesiology
- Critical Care Medicine
Background:
- Post-cardiopulmonary bypass hypotension is a common clinical challenge.
- Synthetic nitric oxide synthase inhibitors, like MTR-105, show experimental promise in rapidly elevating blood pressure.
Purpose of the Study:
- To evaluate the hemodynamic impact of MTR-105 in patients immediately following cardiopulmonary bypass during open-heart surgery.
Main Methods:
- Thirty-six patients with preserved ejection fraction were randomized to receive MTR-105 (50 or 10 microg kg(-1) min(-1)) or placebo for 6 hours post-surgery.
- Hemodynamic variables were monitored for 24 hours post-operation.
- Adverse events were recorded up to 30 days.
Main Results:
- Both MTR-105 doses significantly increased systemic blood pressure (16%) and systemic vascular resistance compared to placebo.
- A decrease in cardiac index was observed with MTR-105 administration.
- The calculated half-life of MTR-105 was approximately 4.1-4.45 hours.
Conclusions:
- MTR-105 demonstrated hemodynamic activity by increasing blood pressure at the tested doses.
- Further research may explore its role in managing post-cardiopulmonary bypass hypotension.
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