Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

James J. Ley, Ricardo Prado, Jianqin Wei, Nanette Bishopric, David A. Becker, Myron Ginsberg

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion. Methods and results: Physiologically controlled male Sprague-Dawley rats were anesthetized with isoflurane, paralyzed with pancuronium and mechanically ventilated. A guide wire was introduced via the femoral artery and advanced retrogradely via the aorta into the left coronary artery under fluoroscopic guidance. Rats with established coronary ischemia (85 min after occlusion) were given STAZN 3.5 mg/kg or its vehicle 5 min before and 2 h after reperfusion, and were subjected to functional and histopathologic studies at 3 days. Ischemia-associated Q wave amplitude was reduced by 73% in STAZN-treated rats (P = 0.01), while infarct-related ejection fraction, fractional shortening and severe regional wall-motion impairments were improved by 48%, 54% and 37%, respectively, relative to vehicle-treated controls (P = 0.05). Total myocardial infarct volume in STAZN-treated rats was correspondingly reduced by 43% (P < 0.05), representing a sparing of 14% of the total left ventricular myocardium. Conclusions: STAZN, a second-generation azulenyl nitrone with potent neuroprotective efficacy in brain ischemia, is also a rapidly acting and highly effective cardioprotective agent in acute coronary ischemia. Our results suggest the potential for clinical benefit in the setting of acute coronary syndromes.

Original languageEnglish
Pages (from-to)448-456
Number of pages9
JournalBiochemical Pharmacology
Volume75
Issue number2
DOIs
StatePublished - Jan 15 2008

Fingerprint

Myocardial Reperfusion Injury
Reperfusion Injury
Myocardial Ischemia
Antioxidants
Rats
Ischemia
Reperfusion
Myocardium
Myocardial Infarction
Cardiotonic Agents
Pancuronium
Free Radical Scavengers
Oxidative stress
Coronary Occlusion
Isoflurane
Femoral Artery
Acute Coronary Syndrome
Brain Ischemia
Sprague Dawley Rats
Aorta

Keywords

  • Antioxidants
  • Free radicals
  • Ischemia
  • Myocardial infarction
  • Reperfusion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury. / Ley, James J.; Prado, Ricardo; Wei, Jianqin; Bishopric, Nanette; Becker, David A.; Ginsberg, Myron.

In: Biochemical Pharmacology, Vol. 75, No. 2, 15.01.2008, p. 448-456.

Research output: Contribution to journalArticle

Ley, James J. ; Prado, Ricardo ; Wei, Jianqin ; Bishopric, Nanette ; Becker, David A. ; Ginsberg, Myron. / Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury. In: Biochemical Pharmacology. 2008 ; Vol. 75, No. 2. pp. 448-456.
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AU - Becker, David A.

AU - Ginsberg, Myron

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AB - Background: Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion. Methods and results: Physiologically controlled male Sprague-Dawley rats were anesthetized with isoflurane, paralyzed with pancuronium and mechanically ventilated. A guide wire was introduced via the femoral artery and advanced retrogradely via the aorta into the left coronary artery under fluoroscopic guidance. Rats with established coronary ischemia (85 min after occlusion) were given STAZN 3.5 mg/kg or its vehicle 5 min before and 2 h after reperfusion, and were subjected to functional and histopathologic studies at 3 days. Ischemia-associated Q wave amplitude was reduced by 73% in STAZN-treated rats (P = 0.01), while infarct-related ejection fraction, fractional shortening and severe regional wall-motion impairments were improved by 48%, 54% and 37%, respectively, relative to vehicle-treated controls (P = 0.05). Total myocardial infarct volume in STAZN-treated rats was correspondingly reduced by 43% (P < 0.05), representing a sparing of 14% of the total left ventricular myocardium. Conclusions: STAZN, a second-generation azulenyl nitrone with potent neuroprotective efficacy in brain ischemia, is also a rapidly acting and highly effective cardioprotective agent in acute coronary ischemia. Our results suggest the potential for clinical benefit in the setting of acute coronary syndromes.

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