(Circulation. 1995;91:2989-2994.)
© 1995 American Heart Association, Inc.
Articles |
Absence of Lethal Reperfusion Injury After 3 Hours of Reperfusion
A Study in a Single-Canine-Heart Model of Ischemia-Reperfusion
From the Division of Cardiology, Department of Medicine, and the Departments of Pathology (M.C.F.) and Cardiothoracic Surgery (A.C.), Cedars-Sinai Medical Center and the University of California School of Medicine, Los Angeles.
Correspondence to William Ganz, MD, Division of Cardiology, Room 5313, 8700 Beverly Blvd, Los Angeles, CA 90048.
Background Whether reperfusion can cause necrosis of previously viable myocytes (lethal reperfusion injury) remains controversial. Numerous studies examined the ability of various agents to prevent or limit reperfusion injury, but the results were contradictory. In a single-canine-heart model of ischemia-reperfusion, we previously demonstrated that 5 minutes of reperfusion does not increase the transmural extent of necrosis. Since the 5-minute period of reperfusion is considered by some to be too short for the full manifestation of reperfusion injury, we reexamined the issue of lethal reperfusion injury using a modification of the single-heart model of ischemia-reperfusion that allowed extending the reperfusion period to 3 hours.
Methods and Results In anesthetized, open-chest dogs, the distal half of the left anterior descending coronary artery (LAD) segment between the last diagonal branch and the apex was perfused via a shunt from the left carotid artery. The shunt was closed for periods of 90 to 180 minutes, depending on the ECG severity of ischemia, and reperfused for 3 hours. While the distal region was perfused from the carotid artery, the LAD was occluded proximal to the last diagonal branch for the same period of time as the distal region had been earlier. The time of occlusion was chosen such that the end of the occlusion period coincided with the end of the experiment. Thus, both regions of the LAD territory were subjected to identical periods of ischemia, but only the distal region was reperfused. At the end of the experiment, the boundary between the proximal (nonreperfused) and distal (reperfused) area was delineated by blue dye, and the heart was arrested, cut into slices 1 cm thick parallel to the LAD, and placed in triphenyltetrazolium chloride. The epicardial edges of necrosis in the reperfused and the nonreperfused regions were examined for any shift that might suggest a difference in the transmurality of necrosis. The areas of necrotic and viable myocardium were measured by planimetry within 1 cm on either side of the boundary. In all 14 dogs, the epicardial edges of necrosis ran as a single line across the boundary, and no shift was present. There was also no difference in the transmurality of necrosis between the reperfused and nonreperfused regions (64.9±20.7% versus 66.1±17.0% of left ventricular wall thickness, respectively; P=.32 by paired t test).
Conclusions In a single-canine-heart model of ischemia-reperfusion, there was no evidence of lethal reperfusion injury after 3 hours of reperfusion.
Key Words: myocardial infarction • ischemia • reperfusion
This article has been cited by other articles:
 |
|
 |
|
  F. Vetterlein, C. Schrader, R. Volkmann, M. Neckel, M. Ochs, G. Schmidt, and G. Hellige Extent of damage in ischemic, nonreperfused, and reperfused myocardium of anesthetized rats Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H755 - H765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Coggins, J. Sklenar, D. E. Le, K. Wei, J. R. Lindner, and S. Kaul Noninvasive Prediction of Ultimate Infarct Size at the Time of Acute Coronary Occlusion Based on the Extent and Magnitude of Collateral-Derived Myocardial Blood Flow Circulation, November 13, 2001; 104(20): 2471 - 2477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Becker, R. W. Jeremy, J. Schaper, and W. Schaper Ultrastructural assessment of myocardial necrosis occurring during ischemia and 3-h reperfusion in the dog Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H243 - H252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hattori, H. Matsui, M. Kitano, Y. Ichihara, S. Ogawa, M. Hirai, H. Hayashi, and H. Saito Staged Reperfusion Preserves the Coronary Flow Reserve, Especially in the Regions Not Severely Damaged by Ischemic Injury in the Canine Heart Angiology, December 1, 1998; 49(12): 991 - 1004. [Abstract] [PDF]
|
|
|
|
|
|
B. Ghaleh, Y.-T. Shen, and S. F. Vatner Spatial Heterogeneity of Myocardial Blood Flow Presages Salvage Versus Necrosis With Coronary Artery Reperfusion in Conscious Baboons Circulation, November 1, 1996; 94(9): 2210 - 2215. [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]
|
|