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

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

Methods and results: twenty-five patients with severe chronic HF were recruited. Eight received short-term (5 minutes) intravenous NaNO2 at 10 ?g/kg/min and 17 received 50 ?g/kg/min with measurement of cardiac hemodynamics. During infusion of 50 ?g/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 ?g/kg/min; this was significant only for stroke volume, not for other parameters.

Conclusions: 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
heart failure, hemodynamics, methemoglobinemia, nitric oxide, nitrite
1941-3297
565-571
Ormerod, Julian O.M.
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Arif, Sayqa
ed43541d-4eaf-4397-9028-88b9571effff
Mukadam, Majid
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Evans, Jonathan D.W.
15536695-38f8-4678-a90c-9b20079c05d9
Beadle, Roger
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Fernandez, Bernadette O.
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Bonser, Robert S.
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Feelisch, Martin
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Madhani, Melanie
63a48cca-67b7-41ae-bc79-0f4a166f0750
Frenneaux, Michael P.
82824b6d-51f1-4b31-9f7a-5b4746d59833
Ormerod, Julian O.M.
0c5adcde-df48-48ef-bbad-d40e53fd77fe
Arif, Sayqa
ed43541d-4eaf-4397-9028-88b9571effff
Mukadam, Majid
f529efd3-9971-43a9-b4fc-8ae43f828650
Evans, Jonathan D.W.
15536695-38f8-4678-a90c-9b20079c05d9
Beadle, Roger
8d15e7b4-5ca6-450f-a4e3-70d6545dc134
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Bonser, Robert S.
a9b2ab67-2e16-4fae-a264-d0ac2167806d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Madhani, Melanie
63a48cca-67b7-41ae-bc79-0f4a166f0750
Frenneaux, Michael P.
82824b6d-51f1-4b31-9f7a-5b4746d59833

Ormerod, Julian O.M., Arif, Sayqa, Mukadam, Majid, Evans, Jonathan D.W., Beadle, Roger, Fernandez, Bernadette O., Bonser, Robert S., Feelisch, Martin, Madhani, Melanie and Frenneaux, Michael P. (2015) Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients. Circulation: Heart failure, 8 (3), 565-571. (doi:10.1161/CIRCHEARTFAILURE.114.001716). (PMID:25838311)

Record type: Article

Abstract

Background: 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.

Methods and results: twenty-five patients with severe chronic HF were recruited. Eight received short-term (5 minutes) intravenous NaNO2 at 10 ?g/kg/min and 17 received 50 ?g/kg/min with measurement of cardiac hemodynamics. During infusion of 50 ?g/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 ?g/kg/min; this was significant only for stroke volume, not for other parameters.

Conclusions: 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

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Published date: 19 May 2015
Keywords: heart failure, hemodynamics, methemoglobinemia, nitric oxide, nitrite
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 378740
URI: https://eprints.soton.ac.uk/id/eprint/378740
ISSN: 1941-3297
PURE UUID: 16732c34-7397-4bf4-afe3-7019a43943fd
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 09 Jul 2015 12:47
Last modified: 17 Jul 2019 20:26

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Contributors

Author: Julian O.M. Ormerod
Author: Sayqa Arif
Author: Majid Mukadam
Author: Jonathan D.W. Evans
Author: Roger Beadle
Author: Bernadette O. Fernandez
Author: Robert S. Bonser
Author: Martin Feelisch ORCID iD
Author: Melanie Madhani
Author: Michael P. Frenneaux

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