Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial

Br J Anaesth. 2021 Oct;127(4):547-555. doi: 10.1016/j.bja.2021.06.046. Epub 2021 Aug 14.

Abstract

Background: Nitric oxide (NO) is an important signalling molecule in the cardiovascular system with protective properties in ischaemia-reperfusion injury. Inorganic nitrate, an oxidation product of endogenous NO production and a constituent in our diet, can be recycled back to bioactive NO. We investigated if preoperative administration of inorganic nitrate could reduce troponin T release and other plasma markers of injury to the heart, liver, kidney, and brain in patients undergoing cardiac surgery.

Methods: This single-centre, randomised, double-blind, placebo-controlled trial included 82 patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Oral sodium nitrate (700 mg×2) or placebo (NaCl) were administered before surgery. Biomarkers of ischaemia-reperfusion injury and plasma nitrate and nitrite were collected before and up to 72 h after surgery. Troponin T release was our predefined primary endpoint and biomarkers of renal, liver, and brain injury were secondary endpoints.

Results: Plasma concentrations of nitrate and nitrite were elevated in nitrate-treated patients compared with placebo. The 72-h release of troponin T did not differ between groups. Other plasma biomarkers of organ injury were also similar between groups. Blood loss was not a predefined outcome parameter, but perioperative bleeding was 18% less in nitrate-treated patients compared with controls.

Conclusion: Preoperative administration of inorganic nitrate did not influence troponin T release or other plasma biomarkers of organ injury in cardiac surgery.

Clinical trial registration: NCT01348971.

Keywords: bleeding; cardiac surgery; ischaemia-reperfusion injury; nitrate; nitric oxide; nitrite; perioperative.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Loss, Surgical
  • Cardiopulmonary Bypass / methods*
  • Coronary Artery Bypass / methods*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / therapy*
  • Nitrates / administration & dosage
  • Nitrates / pharmacology*
  • Nitric Oxide / metabolism
  • Preoperative Care / methods
  • Troponin T / blood

Substances

  • Biomarkers
  • Nitrates
  • Troponin T
  • Nitric Oxide
  • sodium nitrate

Associated data

  • ClinicalTrials.gov/NCT01348971