This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ohnishi, Y. Articles by Goldstein, J. A. Search for Related Content PubMed PubMed Citation Articles by Ohnishi, Y. Articles by Goldstein, J. A.

(Circulation. 1995;92:500-510.)
© 1995 American Heart Association, Inc.

Articles

Deleterious Effects of a Systemic Lytic State on Reperfused Myocardium

Minimization of Reperfusion Injury and Enhanced Recovery of Myocardial Function by Direct Angioplasty

Presented in part in abstract form at the American Heart Association Scientific Sessions, Dallas, Tex, 1994, and at the American College of Cardiology Scientific Session, New Orleans, La, 1995.

Yoshio Ohnishi, MD; Michelle C. Butterfield, PhD; Jeffrey E. Saffitz, MD, PhD; Burton E. Sobel, MD; Peter B. Corr, PhD; James A. Goldstein, MD

From the Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Mo.

Background The beneficial effects of flow restoration and the deleterious impact of reperfusion injury on ischemic myocardium are well known. However, most experimental studies have induced reperfusion by mechanical release of nonthrombotic occlusions, only occasionally in the presence of a systemic lytic state. Conditions differ markedly in patients undergoing pharmacological or mechanical recanalization of thrombotically occluded coronary arteries. Accordingly, this study was designed to determine whether the method of coronary occlusion and mode of recanalization influence the response of the heart to reperfusion.

Methods and Results The acute effects of reperfusion on right ventricular (RV) function and histology were studied in open-chest dogs subjected to right coronary artery (RCA) balloon occlusion and deflation alone (group 1), pharmacological lysis of thrombotic occlusions (group 2), balloon occlusion with reperfusion induced by balloon deflation in the presence of a systemic lytic state (group 3), and recanalization of thrombotically occluded vessels by direct angioplasty (group 4). In all groups, 1 hour of RCA occlusion led to RV free wall (FW) dyskinesis. In group 1, reperfusion promptly improved RVFW function, with normal RVFW thickness and only minimal edema by microscopy. In contrast, in group 2, clot lysis led to acute RVFW swelling and impaired recovery of RVFW contraction associated with striking interstitial edema, contraction band necrosis, and hemorrhage by microscopy. In group 3, balloon deflation in the presence of a lytic state led to a similar but less severe pattern of abrupt RVFW swelling and impaired recovery of RVFW function but lesser histological alterations than in group 2. However, mechanical recanalization of thrombotically occluded vessels (group 4) led to prompt recovery of RVFW function without significant RVFW swelling or histological abnormalities.

Conclusions Our observations indicate that the responses of ischemic myocardium to reperfusion are influenced by factors beyond those effects attributable to ischemia and reperfusion per se. Pharmacological lysis of coronary thrombi results in alterations characteristic of reperfusion injury and associated with impaired functional recovery. Such changes are also evident, although to a lesser extent, when reperfusion of nonthrombotic occlusions is induced by mechanical recanalization in the presence of a systemic lytic state but not in its absence. However, such effects were not seen with direct mechanical recanalization of thrombotically occluded vessels. In aggregate, these findings indicate that induction of a systemic lytic state, together with products released by lysis of intracoronary thrombi, generates an injurious milieu that exerts adverse effects on reperfused myocardium.

Key Words: reperfusion • thrombolysis • angioplasty • myocardium

This article has been cited by other articles:

				G. W. Stone Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part I: Primary Percutaneous Coronary Intervention Circulation, July 29, 2008; 118(5): 538 - 551. [Full Text] [PDF]

				G. W. Stone Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part II: Intervention After Fibrinolytic Therapy, Integrated Treatment Recommendations, and Future Directions Circulation, July 29, 2008; 118(5): 552 - 566. [Full Text] [PDF]

				T. R. Bowers, W. W. O'Neill, C. Grines, M. C. Pica, R. D. Safian, and J. A. Goldstein Effect of Reperfusion on Biventricular Function and Survival after Right Ventricular Infarction N. Engl. J. Med., April 2, 1998; 338(14): 933 - 940. [Abstract] [Full Text] [PDF]

				S. V. Pislaru, L. Barrios, T. Stassen, L. Jun, C. Pislaru, and F. Van de Werf Infarct Size, Myocardial Hemorrhage, and Recovery of Function After Mechanical Versus Pharmacological Reperfusion : Effects of Lytic State and Occlusion Time Circulation, July 15, 1997; 96(2): 659 - 666. [Abstract] [Full Text]