Circulation, Vol 83, 237-247, Copyright © 1991 by American Heart Association
CJ Pitarys 2d, R Virmani, HD Vildibill Jr, EK Jackson and MB Forman
Adenosine influences the function of several cell types thought to be
involved in the pathogenesis of myocardial reperfusion injury. We have
previously demonstrated that intracoronary administration of adenosine
enhances myocardial salvage 24 hours after reperfusion. To determine if
these beneficial effects could be obtained during a prolonged period of
reperfusion using an intravenous route of administration, 22 closed- chest
dogs were subjected to 90 minutes of proximal left anterior descending
coronary artery occlusion and 72 hours of reperfusion. Animals randomly
received either intravenous adenosine (0.15 mg/kg/min) or an equal volume
of Ringer's lactate during the first 150 minutes of reperfusion. The area
at risk was defined in vivo with Monastral blue, and infarct size was
measured histologically with Mallory's trichrome stain. Serial global and
regional ventricular function were determined with contrast
ventriculography and analyzed using a computerized radial shortening
method. Biopsies were obtained from the central ischemic zone to assess
endothelial ultrastructure and capillary obstruction. No significant
effects in heart rate or blood pressure were noted during adenosine
infusion. Transmural collateral blood flow during ischemia was similar in
the groups. Infarct size expressed as a percentage of the anatomical area
at risk was significantly less in the adenosine- treated group (35.3 +/-
4.3% in controls versus 17.1 +/- 4.3% in treated animals, p less than
0.01). A progressive decrease in transmural blood flow was noted in control
animals during reperfusion, resulting in a significant reduction at 3 hours
compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline
versus 0.45 +/- 0.10 ml/min/g at 3 hours, p less than 0.05]). In contrast,
flow in adenosine animals at 3 hours was similar to baseline values (0.91
+/- 0.15 ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p =
NS) and was significantly higher (p less than 0.05) than the control group.
Radial shortening in the ischemic zone was significantly improved at 3
(-2.6 +/- 2.8% in controls versus 11.6 +/- 3.3% in treated animals, p less
than 0.01) and 72 hours (5.5 +/- 2.0% in controls versus 17.3 +/- 3.5% in
treated animals, p less than 0.01) after reperfusion in treated animals.
Electron microscopy showed reduced neutrophil and erythrocyte plugging of
capillaries with relative preservation of endothelial cell structure in the
adenosine group.(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.
This article has been cited by other articles:
 |
|
 |
|
  M. L. Fokkema, P. J. Vlaar, M. Vogelzang, Y. L. Gu, M. A. Kampinga, B. J. de Smet, G. A. Jessurun, R. L. Anthonio, A. F. van den Heuvel, E.-S. Tan, et al. Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial Circ Cardiovasc Interv, August 1, 2009; 2(4): 323 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Granfeldt, D. J. Lefer, and J. Vinten-Johansen Protective ischaemia in patients: preconditioning and postconditioning Cardiovasc Res, July 15, 2009; 83(2): 234 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Cohen and J. M. Downey Adenosine at reperfusion a conundrum ready to be resolved. J. Am. Coll. Cardiol., February 24, 2009; 53(8): 718 - 719. [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Liem, H. M. Honda, J. Zhang, D. Woo, and P. Ping Past and present course of cardioprotection against ischemia- reperfusion injury J Appl Physiol, December 1, 2007; 103(6): 2129 - 2136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Gross and G. J. Gross Ligand triggers of classical preconditioning and postconditioning Cardiovasc Res, May 1, 2006; 70(2): 212 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ross, R. J. Gibbons, G. W. Stone, R. A. Kloner, R. W. Alexander, and for the AMISTAD-II Investigators A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Adenosine as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction (AMISTAD-II) J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1775 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Glover, L. M. Riou, M. Ruiz, G. W. Sullivan, J. Linden, J. M. Rieger, T. L. Macdonald, D. D. Watson, and G. A. Beller Reduction of infarct size and postischemic inflammation from ATL-146e, a highly selective adenosine A2A receptor agonist, in reperfused canine myocardium Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1851 - H1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vinten-Johansen, Z.-Q. Zhao, J. S. Corvera, C. D. Morris, J. M. Budde, V. H. Thourani, and R. A. Guyton Adenosine in myocardial protection in on-pump and off-pump cardiac surgery Ann. Thorac. Surg., February 1, 2003; 75(2): S691 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Maddock, M. M. Mocanu, and D. M. Yellon Adenosine A3 receptor activation protects the myocardium from reperfusion/reoxygenation injury Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1307 - H1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Stangl, G. Baumann, K. Stangl, and S. B Felix Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion Cardiovasc Res, January 1, 2002; 53(1): 12 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Smolenski, O. Raisky, E. M. Slominska, H. Abunasra, K. K. Kalsi, J. Jayakumar, K. Suzuki, and M. H. Yacoub Protection From Reperfusion Injury After Cardiac Transplantation by Inhibition of Adenosine Metabolism and Nucleotide Precursor Supply Circulation, September 18, 2001; 104 (2009): I-246 - I-252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Lasley, M. S. Jahania, and R. M. Mentzer Jr. Beneficial effects of adenosine A2a agonist CGS-21680 in infarcted and stunned porcine myocardium Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1660 - H1666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M Budde, D. A Velez, Z.-Q. Zhao, K. L Clark, C. D Morris, S. Muraki, R. A Guyton, and J. Vinten-Johansen Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion Cardiovasc Res, August 1, 2000; 47(2): 294 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Forman, J. V. Vitola, C. E. Velasco, J. J. Murray, R. K. Dubey, and E. K. Jackson Sustained Reduction in Myocardial Reperfusion Injury with an Adenosine Receptor Antagonist: Possible Role of the Neutrophil Chemoattractant Response J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 929 - 938. [Abstract] [Full Text]
|
|
|
|
 |
|
 W. R. Ford, A. S. Clanachan, and B. I. Jugdutt Characterization of Cardioprotection Mediated by AT2 Receptor Antagonism After Ischemia-Reperfusion in Isolated Working Rat Hearts Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(3): 211 - 221. [Abstract] [PDF]
|
|
|
|
|
|
K. W. Mahaffey, J. A. Puma, N. A. Barbagelata, M. F. DiCarli, M. A. Leesar, K. F. Browne, P. R. Eisenberg, R. Bolli, A. C. Casas, V. Molina-Viamonte, et al. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: Results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) Trial J. Am. Coll. Cardiol., November 15, 1999; 34(6): 1711 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vinten-Johansen, V. H. Thourani, R. S. Ronson, J. E. Jordan, Z.-Q. Zhao, M. Nakamura, D. Velez, and R. A. Guyton Broad-spectrum cardioprotection with adenosine Ann. Thorac. Surg., November 1, 1999; 68(5): 1942 - 1948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Andresen, D. G. Gillespie, Z. Mi, R. K. Dubey, and E. K. Jackson Role of Adenosine A1 Receptors in Modulating Extracellular Adenosine Levels J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 76 - 80. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Wan and A. P.C. Yim Cytokines in myocardial injury: impact on cardiac surgical approach Eur. J. Cardiothorac. Surg., September 1, 1999; 16(suppl_1): S107 - S111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Jordan, Z.-Q. Zhao, and J. Vinten-Johansen The role of neutrophils in myocardial ischemia-reperfusion injury Cardiovasc Res, September 1, 1999; 43(4): 860 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matsumura, R. W. Jeremy, J. Schaper, and L. C. Becker Progression of Myocardial Necrosis During Reperfusion of Ischemic Myocardium Circulation, March 3, 1998; 97(8): 795 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Auchampach, A. Rizvi, Y. Qiu, X.-L. Tang, C. Maldonado, S. Teschner, and R. Bolli Selective Activation of A3 Adenosine Receptors With N6-(3-Iodobenzyl)Adenosine-5'-N-Methyluronamide Protects Against Myocardial Stunning and Infarction Without Hemodynamic Changes in Conscious Rabbits Circ. Res., June 19, 1997; 80(6): 800 - 809. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. L. Capecchi, F. L. Pasini, G. Cati, M. Colafati, A. Acciavatti, L. Ceccatelli, S. Petri, A. de Lalla, T. Di Perri, and P. L. Capecchi Experimental Model of Short-Time Exercise-Induced Preconditioning in POAD Patients Angiology, June 1, 1997; 48(6): 469 - 480. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Minamino, M. Kitakaze, K. Komamura, K. Node, H. Takeda, M. Inoue, M. Hori, and T. Kamada Activation of Protein Kinase C Increases Adenosine Production in the Hypoxic Canine Coronary Artery Through the Extracellular Pathway Arterioscler Thromb Vasc Biol, December 1, 1995; 15(12): 2298 - 2304. [Abstract] [Full Text]
|
|
|
|
|
|
P. R. Hansen Role of Neutrophils in Myocardial Ischemia and Reperfusion Circulation, March 15, 1995; 91(6): 1872 - 1885. [Abstract] [Full Text]
|
|
|
|
|
|
S. Sekili, M. O. Jeroudi, X.-L. Tang, M. Zughaib, J.-Z. Sun, and R. Bolli Effect of Adenosine on Myocardial `Stunning' in the Dog Circ. Res., January 1, 1995; 76(1): 82 - 94. [Abstract] [Full Text]
|
|
|
|
|
|
A. Satani, S. Kawashima, and T. Iwasaki Effects of Intracoronary Infusion of Adenosine on Cumulative Deterioration of Regional Myocardial Wall Motion Induced by Repeated Brief Periods of Coronary occlusion in Anesthetized Dogs Angiology, August 1, 1994; 45(8): 695 - 701. [Abstract] [PDF]
|
|