N-2-mercaptopropionylglycine improves recovery of myocardial function after reversible regional ischemia

Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties, to attenuate postischemic dysfunction in open chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. Treated animals received an infusion of N-2-mercaptopropionylglycine (50 mg/kg per h) for 4 hours starting 15 minutes before coronary occlusion. Collateral flow, as determined with radioactive microspheres after 10 minutes of ischemia, was 0.07 +/- 0.01 ml/min per g (mean +/- SE) in both control (n = 20) and treated (n = 13) groups. The occluded vascular bed, as determined by postmortem perfusion, averaged 26.1 +/- 1.2% of the weight of the left ventricle in control and 29.6 +/- 1.3% in treated animals. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs at 1 hour (44.6 versus 12.8%, p = 0.05), 2 hours (64.0 versus 31.6%, p less than 0.02), 3 hours (77.1 versus 36.7%, p less than 0.01) and 4 hours of reperfusion (75.0 versus 40.0%, p less than 0.05). Thus, N-2-mercaptopropionylglycine produced a significant and sustained improvement in recovery of contractile function after a brief episode of regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				N. Couvreur, L. Lucats, R. Tissier, A. Bize, A. Berdeaux, and B. Ghaleh Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1345 - H1350. [Abstract] [Full Text] [PDF]

				M. Morihira, N. Hasebe, E. Baljinnyam, K. Sumitomo, T. Matsusaka, K. Izawa, T. Fujino, J. Fukuzawa, and K. Kikuchi Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H577 - H583. [Abstract] [Full Text] [PDF]

				M. Canton, I. Neverova, R. Menabo, J. Van Eyk, and F. Di Lisa Evidence of myofibrillar protein oxidation induced by postischemic reperfusion in isolated rat hearts Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H870 - H877. [Abstract] [Full Text] [PDF]

				K. Tanonaka, T. Iwai, K. Motegi, and S. Takeo Effects of N-(2-mercaptopropionyl)-glycine on mitochondrial function in ischemic-reperfused heart Cardiovasc Res, February 1, 2003; 57(2): 416 - 425. [Abstract] [Full Text] [PDF]

				T. O. Nossuli, N. G. Frangogiannis, P. Knuefermann, V. Lakshminarayanan, O. Dewald, A. J. Evans, J. Peschon, D. L. Mann, L. H. Michael, and M. L. Entman Brief murine myocardial I/R induces chemokines in a TNF-alpha -independent manner: role of oxygen radicals Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2549 - H2558. [Abstract] [Full Text] [PDF]

				R. Bolli and E. Marban Molecular and Cellular Mechanisms of Myocardial Stunning Physiol Rev, April 1, 1999; 79(2): 609 - 634. [Abstract] [Full Text] [PDF]

				N. G. Perez, W. D. Gao, and E. Marban Novel Myofilament Ca2+-Sensitizing Property of Xanthine Oxidase Inhibitors Circ. Res., August 24, 1998; 83(4): 423 - 430. [Abstract] [Full Text] [PDF]

				W. D. Gao, Y. Liu, and E. Marban Selective Effects of Oxygen Free Radicals on Excitation-Contraction Coupling in Ventricular Muscle: Implications for the Mechanism of Stunned Myocardium Circulation, November 15, 1996; 94(10): 2597 - 2604. [Abstract] [Full Text]

				M. L. Hess and R. C. Kukreja Free radicals, calcium homeostasis, heat shock proteins, and myocardial stunning Ann. Thorac. Surg., September 1, 1995; 60(3): 760 - 766. [Abstract] [PDF]