Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients

• Published in: Circulation. Heart failure Vol. 8; no. 3; pp. 565 - 571
• Main Authors: Ormerod, Julian O M, Arif, Sayqa, Mukadam, Majid, Evans, Jonathan D W, Beadle, Roger, Fernandez, Bernadette O, Bonser, Robert S, Feelisch, Martin, Madhani, Melanie, Frenneaux, Michael P
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01.05.2015
• Subjects: Adult; Arterial Pressure - drug effects; Cardiac Output - drug effects; Chronic Disease; Coronary Circulation - drug effects; Drug Administration Schedule; England; Female; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Failure - physiopathology; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Male; Middle Aged; Original; Pulmonary Circulation - drug effects; Recovery of Function; Severity of Illness Index; Sodium Nitrite - administration & dosage; Sodium Nitrite - adverse effects; Time Factors; Treatment Outcome; Vascular Resistance - drug effects; Vasodilation - drug effects; Vasodilator Agents - administration & dosage; Vasodilator Agents - adverse effects; England; heart failure; nitric oxide; nitrite; hemodynamics; methemoglobinemia
• ISSN: 1941-3289; 1941-3297
• DOI: 10.1161/circheartfailure.114.001716

Nitrite exhibits hypoxia-dependent vasodilator properties, selectively dilating capacitance vessels in healthy subjects. Unlike organic nitrates, it seems not to be subject to the development of tolerance. Currently, therapeutic options for decompensated heart failure (HF) are limited. We hypothesized that by preferentially dilating systemic capacitance and pulmonary resistance vessels although only marginally dilating resistance vessels, sodium nitrite (NaNO2) infusion would increase cardiac output but reduce systemic arterial blood pressure only modestly. We therefore undertook a first-in-human HF proof of concept/safety study, evaluating the hemodynamic effects of short-term NaNO2 infusion. Twenty-five patients with severe chronic HF were recruited. Eight received short-term (5 minutes) intravenous NaNO2 at 10 μg/kg/min and 17 received 50 μg/kg/min with measurement of cardiac hemodynamics. During infusion of 50 μg/kg/min, left ventricular stroke volume increased (from 43.22±21.5 to 51.84±23.6 mL; P=0.003), with marked falls in pulmonary vascular resistance (by 29%; P=0.03) and right atrial pressure (by 40%; P=0.007), but with only modest falls in mean arterial blood pressure (by 4 mm Hg; P=0.004). The increase in stroke volume correlated with the increase in estimated trans-septal gradient (=pulmonary capillary wedge pressure-right atrial pressure; r=0.67; P=0.003), suggesting relief of diastolic ventricular interaction as a contributory mechanism. Directionally similar effects were observed for the above hemodynamic parameters with 10 μg/kg/min; this was significant only for stroke volume, not for other parameters. This first-in-human HF efficacy/safety study demonstrates an attractive profile during short-term systemic NaNO2 infusion that may be beneficial in decompensated HF and warrants further evaluation with longer infusion regimens.