Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog

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Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog

RL Engler, GW Schmid-Schonbein and RS Pavelec

After several hours of ischemia an incomplete return of blood flow has been reported in brain, kidney, skeletal muscle, and heart. The mechanisms responsible for the no-reflow phenomenon have been unclear, and perivascular edema, platelet or red cell plugs, and interstitial hemorrhage have been implicated. In the present study evidence is provided that leukocyte entrapment in capillaries might contribute to no reflow. Leukocytes are large and stiff cells, which adhere to vascular endothelium naturally and are known to alter in their adherence properties under a variety of conditions. Accordingly, 11 open-chest dogs were studied, 1-5 hours after left anterior descending coronary artery occlusion. Reperfusion (9 dogs) at 75 mm Hg arterial pressure was accomplished with Ringer's lactate and carbon suspension as a marker for capillary patency. In non-ischemic tissue, 98% of the capillaries contained carbon, rare leukocytes, and few erythrocytes, whereas tissue from the distribution of the occluded artery was heterogeneous: 60% of the capillaries had no carbon, high hematocrits, and approximately one leukocyte per unbranched capillary; 40% demonstrated reflow and no leukocytes. A significant correlation between capillaries without carbon (no reflow) and the frequency of leukocytes remaining in these capillaries indicated that leukocytes were present in obstructed capillaries. Furthermore, the frequency of leukocytes remaining after the washout with lactate was ten times greater than in normal arrested heart muscle without washout. Our results suggest that progressive leukocyte capillary plugging during myocardial ischemia contributes to preventing full restoration of capillary flow upon reperfusion.

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Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury
Ann. Thorac. Surg., December 1, 1996; 62(6): 1691 - 1696.
[Abstract] [Full Text]

T. Miura, D. P. Nelson, M. L. Schermerhorn, T. Shin'oka, G. Zund, P. R. Hickey, E. J. Neufeld, and J. E. Mayer Jr
Blockade of Selectin-Mediated Leukocyte Adhesion Improves Postischemic Function in Lamb Hearts
Ann. Thorac. Surg., November 1, 1996; 62(5): 1295 - 1300.
[Abstract] [Full Text]

K. Iwakura, H. Ito, S. Takiuchi, Y. Taniyama, Y. Nakatsuchi, S. Negoro, Y. Higashino, A. Okamura, T. Masuyama, M. Hori, et al.
Alternation in the Coronary Blood Flow Velocity Pattern in Patients With No Reflow and Reperfused Acute Myocardial Infarction
Circulation, September 15, 1996; 94(6): 1269 - 1275.
[Abstract] [Full Text]

G. Caimi, B. Canino, F. Ferrara, M. Montana, F. Meli, A. Catania, and R. Lo Presti
Leukocyte Flow Properties, Polymorphonuclear Membrane Fluidity, and Cytosolic Ca 2+ Content in Subjects with Vascular Atherosclerotic Disease with and Without Noninsulin-Dependent Diabetes Mellitus
Angiology, August 1, 1996; 47(8): 757 - 763.
[Abstract] [PDF]

G. L. Schaer, L. J. Spaccavento, K. F. Browne, K. A. Krueger, D. Krichbaum, J. M. Phelan, W. O. Fletcher, C. L. Grines, S. Edwards, M. K. Jolly, et al.
Beneficial Effects of RheothRx Injection in Patients Receiving Thrombolytic Therapy for Acute Myocardial Infarction: Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Circulation, August 1, 1996; 94(3): 298 - 307.
[Abstract] [Full Text]

G. S. Aldea, X. Zhang, S. Rivers, and R. J. Shemin
Salvage of Ischemic Myocardium With Simplified and Even Delayed Coronary Sinus Retroperfusion
Ann. Thorac. Surg., July 1, 1996; 62(1): 9 - 15.
[Abstract] [Full Text]

C. H. Tinsley, L. R. Tinsley, S. D. Nishida, S. Premaratne, and J. J. McNamara
Measurement of Oxygen Free Radicals in a Rabbit Shock Lung Model: Effect of Superoxide Dismutase and Retinol
Arch Surg, July 1, 1996; 131(7): 738 - 743.
[Abstract] [PDF]

Y. Sawa, K. Taniguchi, K. Kadoba, M. Nishimura, H. Ichikawa, A. Amemiya, T. Kuratani, and H. Matsuda
Leukocyte Depletion Attenuates Reperfusion Injury in Patients With Left Ventricular Hypertrophy
Circulation, May 1, 1996; 93(9): 1640 - 1646.
[Abstract] [Full Text]

B.C. Yang, J.C. Williams, and J.L. Mehta
Protective Effect of Elastase Inhibition Against Myocardial Dysfunction and Injury Induced by Ischemia and Reperfusion in Isolated Rat Hearts
Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1996; 1(1): 31 - 39.
[Abstract] [PDF]

Y. Sawa, Y. Shimazaki, K. Kadoba, T. Masai, H. Fukuda, T. Ohata, K. Taniguchi, and H. Matsuda
ATTENUATION OF CARDIOPULMONARY BYPASS-DERIVED INFLAMMATORY REACTIONS REDUCES MYOCARDIAL REPERFUSION INJURY IN CARDIAC OPERATIONS
J. Thorac. Cardiovasc. Surg., January 1, 1996; 111(1): 29 - 35.
[Abstract] [Full Text]

R. Pabla, A. J. Buda, D. M. Flynn, S. A. Blesse, A. M. Shin, M. J. Curtis, and D. J. Lefer
Nitric Oxide Attenuates Neutrophil-Mediated Myocardial Contractile Dysfunction After Ischemia and Reperfusion
Circ. Res., January 1, 1996; 78(1): 65 - 72.
[Abstract] [Full Text]

J. M. Forbess, T. Hiramatsu, F. Nomura, T. Miura, G. K. Farrington, K. Sokolowski, M. Bree, and J. E. Mayer Jr
Anti-CD11b Monoclonal Antibody Improves Myocardial Function After Six Hours of Hypothermic Storage
Ann. Thorac. Surg., November 1, 1995; 60(5): 1238 - 1244.
[Abstract] [Full Text]

J. P. Slater, M. M.R. Amirhamzeh, O. J. Yano, A. S. Shah, J. P. Starr, R. J. Kaplon, W. Burfeind, P. Pepino, R. E. Michler, E. A. Rose, et al.
Discriminating Between Preservation and Reperfusion Injury in Human Cardiac Allografts Using Heart Weight and Left Ventricular Mass
Circulation, November 1, 1995; 92(9): 223 - 227.
[Abstract] [Full Text]

H. Fukuda, Y. Sawa, K. Kadoba, K. Taniguchi, Y. Shimazaki, and H. Matsuda
Supplement of Nitric Oxide Attenuates Neutrophil-Mediated Reperfusion Injury
Circulation, November 1, 1995; 92(9): 413 - 416.
[Abstract] [Full Text]

M. C. Oz, H. Liao, Y. Naka, A. Seldomridge, D. N. Becker, R. E. Michler, C. R. Smith, E. A. Rose, D. M. Stern, and D. J. Pinsky
Ischemia-Induced Interleukin-8 Release After Human Heart Transplantation : A Potential Role for Endothelial Cells
Circulation, November 1, 1995; 92(9): 428 - 432.
[Abstract] [Full Text]

K. Kaikita, H. Ogawa, H. Yasue, T. Sakamoto, H. Suefuji, H. Sumida, and K. Okumura
Soluble P-Selectin Is Released Into the Coronary Circulation After Coronary Spasm
Circulation, October 1, 1995; 92(7): 1726 - 1730.
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F.-J. Neumann, I. Ott, M. Gawaz, G. Richardt, H. Holzapfel, M. Jochum, and A. Schomig
Cardiac Release of Cytokines and Inflammatory Responses in Acute Myocardial Infarction
Circulation, August 15, 1995; 92(4): 748 - 755.
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R. W. Smalling, S. Feld, N. Ramanna, J. Amirian, P. Felli, W. K. Vaughn, C. Swenson, and A. Janoff
Infarct Salvage With Liposomal Prostaglandin E1 Administered by Intravenous Bolus Immediately Before Reperfusion in a Canine Infarction-Reperfusion Model
Circulation, August 15, 1995; 92(4): 935 - 943.
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M. J. Silver, J. M. Sutton, S. Hook, P. Lee, J. L. Malycky, M. L. Phillips, S. G. Ellis, E. J. Topol, and F. A. Nicolini
Adjunctive Selectin Blockade Successfully Reduces Infarct Size Beyond Thrombolysis in the Electrolytic Canine Coronary Artery Model
Circulation, August 1, 1995; 92(3): 492 - 499.
[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]

				M. O'Donoghue, D. A. Morrow, C. P. Cannon, W. Guo, S. A. Murphy, C. M. Gibson, and M. S. Sabatine Association between baseline neutrophil count, clopidogrel therapy, and clinical and angiographic outcomes in patients with ST-elevation myocardial infarction receiving fibrinolytic therapy Eur. Heart J., April 2, 2008; 29(8): 984 - 991. [Abstract] [Full Text] [PDF]

				J. W. Calvert, S. Gundewar, M. Yamakuchi, P. C. Park, W. M. Baldwin III, D. J. Lefer, and C. J. Lowenstein Inhibition of N-Ethylmaleimide Sensitive Factor Protects Against Myocardial Ischemia/Reperfusion Injury Circ. Res., December 7, 2007; 101(12): 1247 - 1254. [Abstract] [Full Text] [PDF]

				S. Gundewar, J. W. Calvert, J. W. Elrod, and D. J. Lefer Cytoprotective effects of N,N,N-trimethylsphingosine during ischemia- reperfusion injury are lost in the setting of obesity and diabetes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2462 - H2471. [Abstract] [Full Text] [PDF]

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				M. Sezer, I. Okcular, T. Goren, H. Oflaz, Y. Nisanci, B. Umman, F. Mercanoglu, A. K Bilge, M. Meric, and S. Umman Association of haematological indices with the degree of microvascular injury in patients with acute anterior wall myocardial infarction treated with primary percutaneous coronary intervention Heart, March 1, 2007; 93(3): 313 - 318. [Abstract] [Full Text] [PDF]

				J. Tobis, B. Azarbal, and L. Slavin Assessment of Intermediate Severity Coronary Lesions in the Catheterization Laboratory J. Am. Coll. Cardiol., February 27, 2007; 49(8): 839 - 848. [Abstract] [Full Text] [PDF]

				W. J Vermeijden, H. de Vries, J. Kieboom, and T. Waterbolk Leucocyte depletion in a drowning victim during rewarming with extracorporeal circulation may limit pulmonary oedema Perfusion, September 1, 2006; 21(5): 305 - 308. [Abstract] [PDF]

				D. Lewis, H. Goldztein, and D. Deschler Use of hyperbaric oxygen to enhance auricular composite graft survival in the rabbit model. Arch Facial Plast Surg, September 1, 2006; 8(5): 310 - 313. [Abstract] [Full Text] [PDF]

				C.-L. Hang, C.-P. Wang, H.-K. Yip, C.-H. Yang, G. B.-F. Guo, C.-J. Wu, and S.-M. Chen Early Administration of Intracoronary Verapamil Improves Myocardial Perfusion During Percutaneous Coronary Interventions for Acute Myocardial Infarction Chest, October 1, 2005; 128(4): 2593 - 2598. [Abstract] [Full Text] [PDF]

				Y. Koyama, H. Matsuoka, T. Mochizuki, H. Higashino, H. Kawakami, S. Nakata, J. Aono, T. Ito, M. Naka, Y. Ohashi, et al. Assessment of Reperfused Acute Myocardial Infarction with Two-Phase Contrast-enhanced Helical CT: Prediction of Left Ventricular Function and Wall Thickness Radiology, June 1, 2005; 235(3): 804 - 811. [Abstract] [Full Text] [PDF]

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				B. S. Coller Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality: Is It Time to Intervene? Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 658 - 670. [Abstract] [Full Text] [PDF]

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				Y. Onai, J.-i. Suzuki, T. Kakuta, Y. Maejima, G. Haraguchi, H. Fukasawa, S. Muto, A. Itai, and M. Isobe Inhibition of I{kappa}B phosphorylation in cardiomyocytes attenuates myocardial ischemia/reperfusion injury Cardiovasc Res, July 1, 2004; 63(1): 51 - 59. [Abstract] [Full Text] [PDF]

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				T Hozumi, Y Kanzaki, Y Ueda, A Yamamuro, T Takagi, T Akasaka, S Homma, K Yoshida, and J Yoshikawa Coronary flow velocity analysis during short term follow up after coronary reperfusion: use of transthoracic Doppler echocardiography to predict regional wall motion recovery in patients with acute myocardial infarction Heart, October 1, 2003; 89(10): 1163 - 1168. [Abstract] [Full Text] [PDF]

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