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N-Acetylcysteine–Enhanced Contrast Provides Cardiorenal Protection

Division of Cardiology, University of Vermont College of Medicine, Burlington, Vermont

^_* Reprint requests and correspondence: Dr. Markus Meyer, University of Vermont College of Medicine, Fletcher Allen Health Care, McClure 1, Cardiology, 111 Colchester Avenue, Burlington, Vermont 05401 (Email: markus.meyer{at}vtmednet.org).

Objectives: We sought to evaluate the cardiac and renal effects of an N-acetylcysteine (NAC)-enhanced intracoronary radiographic contrast agent.

Background: Recent studies suggest that high-dose NAC provides better protection from contrast-induced nephropathy, and the antioxidant properties of NAC may also provide cardiac protection. The use of angiographic contrast agents as a drug delivery vehicle for cardiorenal protection effects has not been investigated.

Methods: In a pig model of prolonged cardiac ischemia-reperfusion, NAC-enhanced contrast medium was tested and compared with iopamidol contrast only. Myocardium and renal function were assessed after 24 h.

Results: There was no significant difference in the area-at-risk for myocardial infarction (MI) between contrast only and NAC-enhanced contrast medium. In contrast, MI size was about 40% smaller in NAC-enhanced contrast medium–treated animals. These findings were associated with a significant difference in MI morphology. MIs in the NAC-enhanced contrast medium group had a mottled appearance, whereas in the contrast only group they were homogeneous and had a discrete border zone. These differences could explain a higher incidence of periprocedural ventricular arrhythmias in the NAC-enhanced contrast medium group. Histopathological analysis of the myocardium revealed a reduction in programmed cell death by NAC-enhanced contrast medium that may explain the increase in ischemia tolerance. Last, NAC-enhanced contrast medium administration blunted the rise in serum creatinine levels by about 60% and protected from renotubular apotosis.

Conclusions: NAC-enhanced contrast medium reduces MI size and protects renal function in a pig model of ischemia and reperfusion.

Key Words: contrast medium • ischemia • reperfusion • antioxidants

Abbreviations and Acronyms   CIN = contrast-induced nephropathy   DAPI = 4',6-diamidino-2-phenylindole   DCCV = direct countercurrent cardioversion   LAD = left anterior descending artery   NAC = N-acetylcysteine   TTC = (2,3,5)-triphenyltetrazolium chloride   TUNEL = terminal uridine deoxynucleotidyl transferase dUTP nick end labeling

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