(Circulation. 1997;95:701-708.)
© 1997 American Heart Association, Inc.
Articles |
Intracoronary Application of C1 Esterase Inhibitor Improves Cardiac Function and Reduces Myocardial Necrosis in an Experimental Model of Ischemia and Reperfusion
the Johannes Gutenberg-University Mainz, Second Medical Clinic (G.H., O.B., P.B., P.B., H.D., H.J.R., J.M.); the Institute for Neurosurgical Pathophysiology (A.H., O.K.); the Institute for Microbiology and Hygiene (M.L., S.B.); the Institute for Clinical Chemistry (G.H.); and Georg-August-University Gottingen, Department of Immunology (O.G.), Germany.
Correspondence to Dr Georg Horstick, Johannes Gutenberg-University Mainz, Second Medical Clinic, Langenbeckstraße 1, 55101 Mainz, Germany.
Background Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events, including complement activation, leukocyte adhesion, and infiltration and release of diverse mediators, probably play important roles. The present study addresses the possibility of reducing reperfusion damage by the application of C1 esterase inhibitor (C1-INH).
Methods and Results Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1-INH was administered during the first 5 minutes of coronary reperfusion. Compared with the NaCl controls, C1-INH reduced myocardial injury (48.8±7.8% versus 73.4±4.0% necrosis of area at risk, P
.018). C1-INH treatment significantly reduced circulating C3a and slightly attenuated C5a plasma concentrations. Myocardial protection was accompanied by reduced plasma concentration of creatine kinase and troponin-T. C1-INH had no effect on global hemodynamic parameters, but local myocardial contractility was markedly improved in the ischemic zone. In the short-axis view, 137° of the anteroseptal region showed significantly improved wall motion at early and 29° at late reperfusion with C1-INH treatment.
Conclusions C1-INH significantly protects ischemic tissue from reperfusion damage, reduces myocardial necrosis, and improves local cardiac function.
Key Words: myocardial infarction • ischemia • reperfusion • immune system • contractility
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