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Circ Cardiovasc Interv. 2016 Jan;9(1):e002547. doi: 10.1161/CIRCINTERVENTIONS.115.002547.

Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model.

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From the Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown (S.S., J.D.G., J.C.M., D.H.S., J.S.A.); Cardiac Surgery Research Laboratory, Massachusetts General Hospital, Boston, (J.L.G., J.B., J.S.A.); DecImmune Therapeutics, Cambridge, MA (M.S.H., E.M.A., F.S., R.J.P., W.N.); Program in Cellular and Molecular Medicine, Boston Children's Hospital, MA (M.C.C.); Department of Pediatrics, Harvard Medical School, Boston, MA (M.C.C.); and Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia (K.M.K.).



Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion injury. Circulating natural IgM has been shown to play a significant role in mouse models of ischemia-reperfusion injury. A highly conserved self-antigen, nonmuscle myosin heavy chain II, has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against nonmuscle myosin heavy chain II may inhibit IgM binding and reduce injury in a preclinical model of myocardial infarction. Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine myocardial infarction model.


Massachusetts General Hospital miniature swine underwent occlusion of the midleft anterior descending coronary artery for 60 minutes, followed by 1 hour, 5-day, or 21-day reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 before reperfusion resulted in a 49% reduction in infarct size (P<0.005) and a 61% reduction in troponin-T levels (P<0.05) in comparison with saline controls at 5-day reperfusion. Furthermore, m21G6-treated animals recovered 85.4% of their baseline left ventricular function as measured by 2-dimensional transthoracic echocardiography in contrast to 67.1% in controls at 21-day reperfusion (P<0.05).


Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury.


immunology; inflammation; left ventricular function; myocardial infarction; troponin T

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