title: Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients.
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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Julian O M
authors.initials: JO
authors.lastname: Ormerod
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Sayqa
authors.initials: S
authors.lastname: Arif
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Majid
authors.initials: M
authors.lastname: Mukadam
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Jonathan D W
authors.initials: JD
authors.lastname: Evans
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Roger
authors.initials: R
authors.lastname: Beadle
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Bernadette O
authors.initials: BO
authors.lastname: Fernandez
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bonser
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Madhani
authors.affiliation: From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.). m.frenneaux@uea.ac.uk.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Frenneaux
mesh_terms: D000328:Adult; D062186:Arterial Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects*; D004334:Drug Administration Schedule; D004739:England; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects*; D020127:Recovery of Function; D012720:Severity of Illness Index; D012977:Sodium Nitrite / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014665:Vasodilator Agents; D012977:Sodium Nitrite
keywords: heart failure; hemodynamics; methemoglobinemia; nitric oxide; nitrite
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