Circulation Research, Vol 68, 1652-1659, Copyright © 1991 by American Heart Association

ARTICLES

Reduction of canine myocardial infarct size by a diffusible reactive oxygen metabolite scavenger. Efficacy of dimethylthiourea given at the onset of reperfusion

FP Carrea, EJ Lesnefsky, JE Repine, RH Shikes and LD Horwitz
University of Colorado Health Sciences Center, Denver 80262.

A number of scavengers of reactive oxygen metabolites reduce myocardial injury when given before ischemia and reperfusion, but few, if any, have proven to be effective when given near the onset of reperfusion. This is particularly true when infarct size is measured after at least 48 hours of reperfusion, when the full extent of myocardial damage has become apparent. Dimethylthiourea (DMTU) is an extremely diffusible, potent scavenger of hydroxyl radical, hydrogen peroxide, and hypochlorous acid, with a long half-life of 43 hours. Sixteen chloralose-anesthetized dogs underwent 90 minutes of left anterior descending coronary artery (LAD) occlusion followed by 48 hours of reperfusion. Collateral flow was measured by radioactive microspheres. Infarct size and risk area were measured by a postmortem dual-perfusion technique using triphenyl tetrazolium chloride and Evan's blue dye. In eight dogs, therapy with DMTU (500 mg/kg i.v.) was given during the last 15 minutes of ischemia and the first 15 minutes of reperfusion. In eight control dogs, the same volume of 0.9% saline was given during the last 15 minutes of ischemia through the first 15 minutes of reperfusion. Infarct size as a percent of risk area was reduced in the DMTU-treated group compared with the saline-treated controls (DMTU = 42 +/- 4% versus saline = 59 +/- 4%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				D.-F. Yeih, H.-I Yeh, H.-T. Hsin, L.-Y. Lin, F.-T. Chiang, C.-D. Tseng, S.-H. Chu, and Y.-Z. Tseng Dimethylthiourea normalizes velocity-dependent, but not force-dependent, index of ventricular performance in diabetic rats: role of myosin heavy chain isozyme Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1411 - H1420. [Abstract] [Full Text] [PDF]

				E. J. Lesnefsky, D. He, S. Moghaddas, and C. L. Hoppel Reversal of mitochondrial defects before ischemia protects the aged heart FASEB J, July 1, 2006; 20(9): 1543 - 1545. [Abstract] [Full Text] [PDF]

				S. P. Jones, M. R. Hoffmeyer, B. R. Sharp, Y.-S. Ho, and D. J. Lefer Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H277 - H282. [Abstract] [Full Text] [PDF]

				S. Kinugawa, H. Tsutsui, S. Hayashidani, T. Ide, N. Suematsu, S. Satoh, H. Utsumi, and A. Takeshita Treatment With Dimethylthiourea Prevents Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction in Mice : Role of Oxidative Stress Circ. Res., September 1, 2000; 87(5): 392 - 398. [Abstract] [Full Text] [PDF]

				P. Hardy, K. G. Peri, I. Lahaie, D. R. Varma, and S. Chemtob Increased Nitric Oxide Synthesis and Action Preclude Choroidal Vasoconstriction to Hyperoxia in Newborn Pigs Circ. Res., September 1, 1996; 79(3): 504 - 511. [Abstract] [Full Text]

				E. A. Gill, Y. Kong, and L. D. Horwitz An Oligosaccharide Sialyl-Lewisx Analogue Does Not Reduce Myocardial Infarct Size After Ischemia and Reperfusion in Dogs Circulation, August 1, 1996; 94(3): 542 - 546. [Abstract] [Full Text]