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High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

Abstract
We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.
AuthorsMarkus Meyer, Stephen P Bell, Zengyi Chen, Iwan Nyotowidjojo, Richard R Lachapelle, Timothy F Christian, Pamela C Gibson, Friederike F Keating, Harold L Dauerman, Martin M LeWinter
JournalJournal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 36 Issue 4 Pg. 433-41 (Nov 2013) ISSN: 1573-742X [Electronic] Netherlands
PMID23423816 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Contrast Media
  • Free Radical Scavengers
  • Iopamidol
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology)
  • Animals
  • Contrast Media (pharmacology)
  • Coronary Angiography
  • Disease Models, Animal
  • Female
  • Free Radical Scavengers (pharmacology)
  • Iopamidol (pharmacology)
  • Myocardial Infarction (diagnostic imaging, drug therapy)
  • Myocardial Reperfusion Injury (diagnostic imaging, drug therapy)
  • Swine

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