Nitrite therapy is neuroprotective and safe in cardiac arrest survivors

Cameron Dezfulian, Aleksey Alekseyenko, Kunjan R Dave, Ami Raval, Rose Do, Francis Kim, Miguel Perez-Pinzon

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Cardiac arrest results in significant mortality after initial resuscitation due in most cases to ischemia-reperfusion induced brain injury and to a lesser degree myocardial dysfunction. Nitrite has previously been shown to protect against reperfusion injury in animal models of focal cerebral and heart ischemia. Nitrite therapy after murine cardiac arrest improved 22 h survival through improvements in myocardial contractility. These improvements accompanied transient mitochondrial inhibition which reduced oxidative injury to the heart. Based on preliminary evidence that nitrite may also protect against ischemic brain injury, we sought to test this hypothesis in a rat model of asphyxia cardiac arrest with prolonged survival (7 d). Cardiac arrest resulted in hippocampal CA1 delayed neuronal death well characterized in this and other cardiac arrest models. Nitrite therapy did not alter post-arrest hemodynamics but did result in significant (75%) increases in CA1 neuron survival. This was associated with increases in hippocampal nitrite and S-nitrosothiol levels but not cGMP shortly after therapy. Mitochondrial function 1 h after resuscitation trended towards improvement with nitrite therapy. Based on promising preclinical data, the first ever phase I trial of nitrite infusions in human cardiac arrest survivors has been undertaken. We present preliminary data showing low dose nitrite infusion did not result in hypotension or cause methemoglobinemia. Nitrite thus appears safe and effective for clinical translation as a promising therapy against cardiac arrest mediated heart and brain injury.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Volume26
Issue number4
DOIs
StatePublished - May 15 2012

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Keywords

  • Brain ischemia
  • Cardiac arrest
  • Ischemia
  • Nitric oxide
  • Nitrite
  • Reperfusion injury

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cancer Research
  • Physiology

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