Circulation, Vol 82, 1402-1412, Copyright © 1990 by American Heart Association
PS Tsao, N Aoki, DJ Lefer, G Johnson 3d and AM Lefer
Myocardial ischemia and reperfusion have been shown to impair coronary
vasorelaxation to endothelium-dependent vasodilators. To examine the time
course of this dysfunction, occlusion of the left anterior descending (LAD)
coronary artery (90 minutes) was followed by reperfusion for 0, 2.5, 5, 20,
180, or 270 minutes. Coronary arterial rings from the ischemic LAD and
control left circumflex (LCx) arteries were tested for responsiveness to
the endothelium-dependent receptor- mediated vasodilator, acetylcholine
(ACh), and the endothelium- dependent nonreceptor-mediated vasodilator,
A23187, as well as the endothelium-independent vasodilator, NaNO2. ACh
relaxation was not impaired after 90 minutes of ischemia without
reperfusion. However, 2.5 minutes of reperfusion resulted in depressed ACh
responses (36 +/- 10% of control) that was further reduced to 16 +/- 6% at
20 minutes, and remained comparably depressed at every time thereafter.
A23187 vasodilator responses were also attenuated after reperfusion,
although the reduced response occurred later (that is, at 20 minutes).
There was no significant decrease in response to NaNO2 in the LAD at any
time or to any vasodilator in LCx control rings. Treatment with recombinant
human superoxide dismutase (hSOD, 5 mg/kg/hr, that is, 15,545 SOD
units/kg/hr), starting 10 minutes before reperfusion, preserved the
vasodilator response to ACh (82 +/- 6%) and A23187, but treatment with the
hydroxyl ion scavenger N-(2-mercapto proprionyl)-glycine (MPG) (8 mg/kg/hr)
only protected the A23187 response. No damage to the surface of the
endothelium was observed by scanning electron microscopy at any time point.
Myocardial cell damage increased with time of reperfusion as assessed by
increasing plasma CK activities and amounts of necrotic tissue indexed to
area at risk. Significant myocardial injury occurred at 3 hours after
reperfusion. These findings suggest that endothelial dysfunction resulting
in reduced endothelium-derived relaxing factor release occurs before the
development of myocardial cell necrosis and may be due to oxygen-derived
free radicals produced rapidly on reperfusion.
ARTICLES
Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
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B. D. Spiess, C. Ley, S. C. Body, L. C. Siegel, E. P. Stover, R. Maddi, M. D'Ambra, U. Jain, F. Liu, A. Herskowitz, et al. Hematocrit value on intensive care unit entry influences thefrequency of q-wave myocardial infarction after coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., September 1, 1998; 116(3): 460 - 464. [Abstract] [Full Text]
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B. Campbell, Y. K. Shin, R. Scalia, and A. M. Lefer Beneficial effects of N,N,N-trimethylsphingosine following ischemia and reperfusion in the isolated perfused rat heart Cardiovasc Res, August 1, 1998; 39(2): 393 - 400. [Abstract] [Full Text] [PDF]
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A. Budrikis, R. Bolys, Q. Liao, R. Ingemansson, T. Sjoberg, and S. Steen Function of adult pig hearts after 2 and 12 hours of cold cardioplegic preservation Ann. Thorac. Surg., July 1, 1998; 66(1): 73 - 78. [Abstract] [Full Text] [PDF]
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M. Buerke, D. Prüfer, M. Dahm, H. Oelert, J. Meyer, and H. Darius Blocking of Classical Complement Pathway Inhibits Endothelial Adhesion Molecule Expression and Preserves Ischemic Myocardium from Reperfusion Injury J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 429 - 438. [Abstract] [Full Text]
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C. L. Schleien, J. W. Kuluz, and B. Gelman Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1378 - H1385. [Abstract] [Full Text] [PDF]
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D. S. Morse, D. Adams, and B. Magnani Platelet and Neutrophil Activation During Cardiac Surgical Procedures: Impact of Cardiopulmonary Bypass Ann. Thorac. Surg., March 1, 1998; 65(3): 691 - 695. [Abstract] [Full Text] [PDF]
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P. Liu, K. Yin, R. Nagele, and P. Y-K Wong Inhibition of Nitric Oxide Synthase Attenuates Peroxynitrite Generation, but Augments Neutrophil Accumulation in Hepatic Ischemia-Reperfusion in Rats J. Pharmacol. Exp. Ther., March 1, 1998; 284(3): 1139 - 1146. [Abstract] [Full Text]
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J. P. Donnelly, D. M. Raffel, B. L. Shulkin, J. R. Corbett, E. L. Bove, R. S. Mosca, and T. J. Kulik Resting coronary flow and coronary flow reserve in human infants after repair or palliation of congenital heart defects as measured by positron emission tomography J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 103 - 110. [Abstract] [Full Text] [PDF]
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T. Shirai, V. Rao, R. D. Weisel, J. S. Ikonomidis, R.-K. Li, L. C. Tumiati, F. Merante, and D. A. Mickle Preconditioning human cardiomyocytes and endothelial cells J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 210 - 214. [Abstract] [Full Text] [PDF]
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R. Hayward, T. O. Nossuli, and A. M. Lefer Heparinase III Exerts Endothelial and Cardioprotective Effects in Feline Myocardial Ischemia-Reperfusion Injury J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1032 - 1038. [Abstract] [Full Text]
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M. A. Banda, D. J. Lefer, and D. N. Granger Postischemic endothelium-dependent vascular reactivity is preserved in adhesion molecule-deficient mice Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2721 - H2725. [Abstract] [Full Text] [PDF]
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D. Curro, G. Bombardieri, C. Barilaro, P. Di Francesco, C. Varano, G. Possati, and C. Pragliola Time Dependence of Endothelium-Mediated Vasodilation by Intermittent Antegrade Warm Blood Cardioplegia Ann. Thorac. Surg., November 1, 1997; 64(5): 1354 - 1359. [Abstract] [Full Text]
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N. Kaeffer, V. Richard, and C. Thuillez Delayed Coronary Endothelial Protection 24 Hours After Preconditioning : Role of Free Radicals Circulation, October 7, 1997; 96(7): 2311 - 2316. [Abstract] [Full Text]
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T. O. Nossuli, R. Hayward, R. Scalia, and A. M. Lefer Peroxynitrite Reduces Myocardial Infarct Size and Preserves Coronary Endothelium After Ischemia and Reperfusion in Cats Circulation, October 7, 1997; 96(7): 2317 - 2324. [Abstract] [Full Text]
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 R. R. Giraldez, A. Panda, Y. Xia, S. P. Sanders, and J. L. Zweier Decreased Nitric-oxide Synthase Activity Causes Impaired Endothelium-dependent Relaxation in the Postischemic Heart J. Biol. Chem., August 22, 1997; 272(34): 21420 - 21426. [Abstract] [Full Text] [PDF]
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S.-J. Kim, B. Ghaleh, R. K. Kudej, C.-H. Huang, T. H. Hintze, and S. F. Vatner Delayed Enhanced Nitric Oxide–Mediated Coronary Vasodilation Following Brief Ischemia and Prolonged Reperfusion in Conscious Dogs Circ. Res., July 19, 1997; 81(1): 53 - 59. [Abstract] [Full Text]
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M. S. Bayfield, J. R. Lindner, S. Kaul, S. Ismail, M. L. K. Sheil, N. C. Goodman, R. Zacour, and W. D. Spotnitz DEOXYGENATED BLOOD MINIMIZES ADHERENCE OF SONICATED ALBUMIN MICROBUBBLES DURING CARDIOPLEGIC ARREST AND AFTER BLOOD REPERFUSION: EXPERIMENTAL AND CLINICAL OBSERVATIONS WITH MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY J. Thorac. Cardiovasc. Surg., June 1, 1997; 113(6): 1100 - 1108. [Abstract] [Full Text]
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J. Pernow and Q.-D. Wang Endothelin in myocardial ischaemia and reperfusion Cardiovasc Res, March 1, 1997; 33(3): 518 - 526. [Abstract] [PDF]
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A. M. Lefer Nitric Oxide: Nature's Naturally Occurring Leukocyte Inhibitor Circulation, February 4, 1997; 95(3): 553 - 554. [Full Text]
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G. Horstick, A. Heimann, O. Gotze, G. Hafner, O. Berg, P. Boehmer, P. Becker, H. Darius, H.-J. Rupprecht, M. Loos, et al. Intracoronary Application of C1 Esterase Inhibitor Improves Cardiac Function and Reduces Myocardial Necrosis in an Experimental Model of Ischemia and Reperfusion Circulation, February 4, 1997; 95(3): 701 - 708. [Abstract] [Full Text]
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H. Sato, Z.-Q. Zhao, J. E. Jordan, J. C. Todd, R. D. Riley, C. S. Taft, J. W. Hammon Jr., P. Li, X.-l. Ma, and J. Vinten-Johansen BASAL NITRIC OXIDE EXPRESSES ENDOGENOUS CARDIOPROTECTION DURING REPERFUSION BY INHIBITION OF NEUTROPHIL-MEDIATED DAMAGE AFTER SURGICAL REVASCULARIZATION J. Thorac. Cardiovasc. Surg., February 1, 1997; 113(2): 399 - 409. [Abstract] [Full Text]
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J. E. Jordan, Z.-Q. Zhao, H. Sato, S. Taft, and J. Vinten-Johansen Adenosine A2 Receptor Activation Attenuates Reperfusion Injury by Inhibiting Neutrophil Accumulation, Superoxide Generation and Coronary Endothelial Adherence J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 301 - 309. [Abstract] [Full Text]
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X.-F. Niu, G. Ibbotson, and P. Kubes A Balance Between Nitric Oxide and Oxidants Regulates Mast Cell–Dependent Neutrophil–Endothelial Cell Interactions Circ. Res., November 1, 1996; 79(5): 992 - 999. [Abstract] [Full Text]
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R. H. Weiss, D. J. Fretland, D. A. Baron, U. S. Ryan, and D. P. Riley Manganese-based Superoxide Dismutase Mimetics Inhibit Neutrophil Infiltration in Vivo J. Biol. Chem., October 18, 1996; 271(42): 26149 - 26156. [Abstract] [Full Text] [PDF]
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 B.C. Yang, W.W. Nichols, and J.L. Mehta Cardioprotective Effects of Red Blood Cells on Ischemia and Reperfusion Injury in Isolated Rat Heart: Release of Nitric Oxide as a Potential Mechanism Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 1996; 1(4): 297 - 306. [Abstract] [PDF]
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C. P. Tiefenbacher, W. M. Chilian, M. Mitchell, and D. V. DeFily Restoration of Endothelium-Dependent Vasodilation After Reperfusion Injury by Tetrahydrobiopterin Circulation, September 15, 1996; 94(6): 1423 - 1429. [Abstract] [Full Text]
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M. Carrier, A. Khalil, A. Tourigny, B. C. Solymoss, and L. C. Pelletier Effect of L-Arginine on Metabolic Recovery of the Ischemic Myocardium Ann. Thorac. Surg., June 1, 1996; 61(6): 1651 - 1657. [Abstract] [Full Text]
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K. Morita, K. Ihnken, G. D. Buckberg, M. P. Sherman, and L. J. Ignarro Pulmonary Vasoconstriction Due to Impaired Nitric Oxide Production After Cardiopulmonary Bypass Ann. Thorac. Surg., June 1, 1996; 61(6): 1775 - 1780. [Abstract] [Full Text]
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J. P. Gaboury, X.-F. Niu, and P. Kubes Nitric Oxide Inhibits Numerous Features of Mast Cell–Induced Inflammation Circulation, January 15, 1996; 93(2): 318 - 326. [Abstract] [Full Text]
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T. Hiramatsu, J. M. Forbess, T. Miura, and J. E. Mayer Jr Effect of L-Arginine Cardioplegia on Recovery of Neonatal Lamb Hearts After 2 Hours of Cold Ischemia Ann. Thorac. Surg., November 1, 1995; 60(5): 1187 - 1192. [Abstract] [Full Text]
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T. Murohara, S. J. Parkinson, S. A. Waldman, and A. M. Lefer Inhibition of Nitric Oxide Biosynthesis Promotes P-selectin Expression in Platelets : Role of Protein Kinase C Arterioscler Thromb Vasc Biol, November 1, 1995; 15(11): 2068 - 2075. [Abstract] [Full Text]
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