Summary
Although removal of neutrophils from the arterial blood by mechanical filtration has been reported to prevent or reduce the severity of myocardial stunning caused by a 15 minute coronary artery occlusion in the dog, neutrophil filtration does not protect against myocardial dysfunction following a 10-minute occlusion. Nonfilter methods to reduce neutrophil numbers or effectiveness with anti-neutrophil serum, monoclonal anti-CD11b antibodies, or the lipoxygenase inhibitor nafazatrom fail to modify myocardial dysfunction after brief ischemia, even though they effectively reduce infarct size after more prolonged ischemia. The brief durations of ischemia required to produce myocardial stunning but to avoid necrosis are insufficient to produce local activation of complement, formation of chemotactic factors, or activation or infiltration of neutrophils. Microvascular plugging with neutrophils cannot be demonstrated in stunned myocardium, and abnormalities of microvascular function can be dissociated from impaired postischemic myocardial function. Based on the weight of accumulated evidence, neutrophils appear to have no important role in the production of stunned myocardium.
Similar content being viewed by others
References
Bolli R, Patel BS, Jeroudi MO, et al. Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap α-phenyl N-tert-butyl nitrone. J Clin Invest 1988;82:476–485.
Zweier JL, Kuppusamy P, Williams R, et al. Measurement and characterization of postischemic free radical generation in the isolated perfused heart. J Biol Chem 1989;264:18890–18895.
Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocasrdial “stunning” is a manifestation of reperfusion injury. Circ Res 1989;65:607–622.
Hope EJ, Finney RS, Kuppusamy P, et al. In-vivo measurement of free radical mediated reperfusion injury after hypothermic ischemic arrest (Abstr). Circulation 1989;(Suppl)80 II:II295.
Bolli R, Zhu WX, Hartley CJ, et al. Attenuation of dysfunction in the postischemic “stunned” myocardium by dimethylthiourea. Circulation 1987;76:458–468.
Bolli R, Patel BS, Zhu WX, et al. The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction. Am J Physiol 253:H1372–H1380.
Charlat ML, O'Neill PG, Egan JM, et al. Evidence for a pathogenetic role of xanthine oxidase in the “stunned” myocardium. Am J Physiol 1987;252:H566-H577.
Gross GJ, Farber NE, Hardman HF, Warltier DG. Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs. Am J Physiol 1986;250:H372-H377.
Myers ML, Bolli R, Lekich RF, et al. Enhancement of recovery of myocardial function by oxygen free radical scavengers after reversible regional ischemia. Circulation 1985;72:915–921.
Przyklenk K, Kloner RA. Superoxide dismutase plus catalase improves contractile function in the canine model of the “stunned myocardium”. Circ Res 1986;58:148–156.
Romson JL, Hook BG, Kunkel SL, et al. Reduction in the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation 1983;67:1016–1023.
Lucchesi BR, Mullane KM. Leukocytes and ischemiainduced myocardial injury. Annu Rev Pharmacol Toxicol 1986;26:201–224.
Forman MB, Puett DW, Virmani R. Endothelial and myocardial injury during ischemia and reperfusion: Pathogenesis and therapeutic implications. J Am Coll Cardiol 1989;13:450–459.
Litt MR, Jeremy RW, Weisman HF, et al. Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophilmediated reperfusion injury. Circulation 1989;80:1816–1827.
Engler RL, Schmid-Schonbein GW, Pavalel RS. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 1983;111:98–111.
Hori M, Inone M, Kitakazi M, et al. Role of adenosine in hyperemic response of coronary blood flow in microembolization. Am J Physiol 1986;250:H509–518.
Engler R, Covell JW. Granulocytes cause reperfusion ventricular dysfunction after 15 minute ischemia in the dog. Circ Res 1987;61:20–28.
Westlin W, Mullane KM. Alleviation of myocardial stunning by leukocyte and platelet depletion. Circulation 1989;80: 1828–1836.
Jeremy RW, Becker LC. Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion. J Am Coll Cardiol 1989;13:1155–1163.
Kitakaze M, Takashima S, Sato H. Stimulations of adenosine A1 and A2 receptors prevent myocardial stunning (Abstr). Circulation 1990;82: (Suppl III)III37.
O'Neill PG, Charlat ML, Michael LH, et al. Influence of neutrophil depletion on myocardial function and flow after reversible ischemia. Am J Physiol 1989;256:H341-H351.
Mullane KM, Read N, Salmon JA, Moncada S. Role of leukocytes in acute myocardial infarction in anesthetized dogs: Relationship to myocardial salvage by anti-inflammatory drugs. J Pharmacol Exp Ther 1984;228:510–522.
Schott RJ, Nao BS, McClanahan TB, et al. F (ab')2 fragments of anti-Mol (904) monoclonal antibodies do not prevent myocardial stunning. Circ Res 1989;65:1112–1124.
Dana N, Styrt B, Griffin JD, et al. Two functional domains in the phagocyte membrane glycoprotein Mol identified with monoclonal antibodies. J Immunol 1986;137:3259–3263.
Simpson PJ, Todd RFIII, Fantone JC, et al. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest 1988;81:624–629.
O'Neill PG, Charlat ML, Kim H-S, et al. The lipoxygenase inhibitor nafazatrom fails to attenuate postischemic ventricular dysfunction. Cadiovasc Res 1987;21:755–760.
Bednar M, Smith B, Pinto A, Mullane KM. Nafazatrom induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function. Circ Res 1985;57:131–141.
Shea MJ, Murtagh JJ, Jolly SR, et al. Beneficial effects of nafazatrom on ischemic reperfused myocardium. Eur J Pharmacol 1984;102:63–70.
Rossen RD, Swain JL, Michael LH, et al. Selective accumulation of the first component of complement and leukocytes in ischemic canine heart muscle. A possible initiator of an extramyocardial mechanism of ischemic injury. Circ Res 1985;57:119–130.
Rossen RD, Michael LH, Kagiyama A, et al. Mechanism of complement activation after coronary artery occlusion: Evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo. Circ Res 1988;62:572–584.
Go LO, Murry CE, Richard VJ, et al. Myocardial neutrophil accumulation during reperfusion after reversible or irreversible ischemic injury. Am J Physiol 1988;255:H1188-H1198.
Dreyer WJ, Smith CW, Michael LH, et al. Canine neutrophil activation by cardiac lymph obtained during reperfusion of ischemic myocardium. Circ Res 1989;65:1751–1762.
Nicklas JM, Gips SJ. Decreased coronary flow reserve after transient myocardial ischemia in dogs. J Am Coll Cardiol 1989;13:195–199.
Bolli R, Triana JF, Jeroudi MO. Prolonged impairment of coronary vasodilation after reversible ischemia. Evidence for microvascular “stunning”. Circ Res 1990;67:332–343.
Stahl LD, Weiss HR, Becker LC. Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 1988;77:865–872.
Laxson DD, Homans DC, Dai X-Z, et al. Oxygen consumption and coronary reactivity in postischemic myocardium. Circ Res 1989;64:9–20.
Jeremy RW, Stahl L, Gillinov M, et al. Preservation of coronary flow reserve in stunned myocardium. Am J Physiol 1989;256:H1303-H1310.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Becker, L.C. Do neutrophils contribute to myocardial stunning?. Cardiovasc Drug Ther 5, 909–913 (1991). https://doi.org/10.1007/BF00053552
Issue Date:
DOI: https://doi.org/10.1007/BF00053552