Abstract
Platelet-activating factor (PAF) is released in numerous clinical situations. PAF primes or directly activates polymorphonuclear (PMN) leukocytes, which results in release of oxyradicals (O −2 , H2O2, .OH) and hypochlorous acid (HOCl). The authors investigated the effects of PAF (1 µg/kg IV) in the absence and in the presence of antioxidants (superoxide dismutase [SOD], catalase [CAT], dimethylthiourea [DMTU]) and methionine, a quencher of HOCl, on cardiac function and contractility; blood lactate, gases, and pH levels; serum creatine kinase activity (CK); chemiluminescent activity of PMN leukocytes; and cardiac tissue malondialdehyde (MDA) in anesthetized dogs. Hemodynamic measurements and collection of blood samples for various biochemical measurements were made before and at various intervals up to two hours after PAF administration in the presence and absence of various antioxidants.
PAF produced a decrease in indices of cardiac function and contractility and an increase in systemic and pulmonary vascular resistance. There were decreases in the blood pH and PMN leukocyte chemiluminescence and increases in blood lactate, serum CK activity, and tissue MDA content. SOD plus catalase or DMTU plus methionine reduced the effects of PAF on cardiac function and contractility, blood lactate and pH, serum CK, and cardiac tissue MDA. The antioxidants only partially antagonized the deleterious effects of PAF. The combination of SOD + CAT was superior to that of DMTU + methionine in reducing the deleterious effects of PAF.
These results suggest that PAF-induced depression of cardiac function and contractility, and the increase in systemic and pulmonary vascular resistance, may be partly mediated by the release of oxyradicals and HOCl from PMN leukocytes. Antioxidants may be beneficial in reducing the deleterious effects of PAF on the cardiovascular system.
Similar content being viewed by others
References
Allrich JM, McCarthy CA, Hurst JK (1981) Biological reactivity of hypochlorous acid: Implications for microlucidal mechanisms of leukocyte myeloperoxidase. Proc Natl Acad Sci USA 78:21–214.
Aratani H, Nishida Y, Terasawa M, et al. (1988) Effect of etizolam (Depas) on production of superoxide anion by platelet-activating factor and N-formiyl-methionyl-leucylphenylalanine-stimulated guinea pig polymorphonuclear leukocytes. Jpn J Pharmacol 47: 200–203.
Babior BM (1984) The respiratory burst of phagocytes. J Clin Invest 73:599–601.
Berti F, Magni F, Rossoni G, et al. (1990) Production and biologic interactions of prostacyclin and platelet-activating factor in acute myocardial ischemia in the perfused rabbit heart. J Cardiovasc Pharmacol 16:727–732.
Bessin P, Bonnet J, Apffel P, et al. (1983) Acute circulatory collapse caused by platelet-activating factor (PAF-acether) in dogs. Eur J Pharmacol 86:403–413.
Boli R, Zhu WX, Harley CJ, et al. (1987) Attenuation of dysfunction in postischemic “stunned” myocardium by dimethylthiourea. Circulation 76:458–468.
Braquet P, Paubert-Braquet M, Vangaffig BB (1987) Platelet-activating factor, a potential mediator of shock. In: Advances in Prostaglandin, Thromboxane and Leukotriene Research, Samuelsson B, et al. (eds). Raven Press: New York, pp 818–823.
Burton KP, McCord JM, Ghai G (1984) Myocardial alterations due to free radical generation. Am J Physiol 246:H776-H783.
Campbell AK, Holt ME, Patel A (1984) Chemiluminescence in medical biochemistry. In: Recent Advances in Clinical Chemistry, Albertin GMM and Price CP (eds). Churchill Livingstone: Edinburgh, pp 1–30.
Camussi G, Aglietta M, Malavas F, et al. (1983a) The release of platelet-activating factor from human endothelial cells in culture. J Immunol 131:2397–2403.
Camussi G, Bussolino F, Tetta C, et al. (1983b) Biosynthesis and release of platelet-activating factor from human monocytes. Int Arch Allergy Appl Immunol 70:245–251.
Chignard M, LeCouedic JP, Tencé M, et al. (1979) Role of platelet-activating factor in platelet aggregation. Nature 275:799–800.
Chignard M, LeCouedic JP, Vargaftig BB, et al. (1980) Platelet-activating factor (PAF-acether) secretion from platelets: Effect of aggregating agents. Br J Haematol 46:455–464.
Chung KF, Barnes PJ (1988) PAF antagonists. Their potential therapeutic role in asthma. Drugs 35:93–103.
Daniel WW (1978) Biostatistics: A foundation for analysis in the health sciences. John Wiley & Sons: New York, p 219.
Dochher TW, Wu MS, Robbins JC, et al. (1985) Platelet-activating factor (PAF) involvement in endotoxin-induced hypotension in rats: Studies with PAF-receptor antagonist kadsurenone. Biochem Biophys Res Commun 127:799–808.
Englburger W, Bitter-Suermann D, Hadding U (1987) Influence of lysophospholipids and PAF on the oxidative burst of PMNL. Int J Immuno-pharmacol 9:275–282.
Fantone JC, Ward PA (1982) Role of oxygen-derived free radicals and metabolites in leukocytes-dependent inflammatory reactions. Am J Pathol 107:397–417.
Feuerstein G, Lux WE, Synder F, et al. (1984a) Hypotension produced by platelet-activating factor is reversed by thyrotropin-releasing hormone. Circ Shock 13:255–260.
Feuerstein G, Boyd LM, Ezra D, et al. (1984b) Effect of platelet activating factor on coronary circulation of the domestic pig. Am J Physiol 246:H466-H471.
Freeman BA, Crapo JD (1982) Biology of disease. Free radicals and tissue injury. Lab Invest 47:412–426.
Gonzalez-Crussi F, Hsueh W (1983) Experimental model of ischemic bowel necrosis: The role of platelet-activating factor and endotoxin. Am J Pathol 112:127–135.
Hess HL, Okabe E, Kontos HA (1981) Proton and free oxygen radical interaction with calcium transport system of cardiac sarcoplasmic reticulum. J Mol Cell Cardiol 13:767–772.
Kenzora JL, Perez JE, Bergmann SR, et al. (1984) Effects of acetylglyceryl ether of phosphorylcholine (platelet-activating factor) on ventricular preload, afterload and contractility in dog. J Clin Invest 74:1193–1203.
Kroegel C (1988) The potential pathophysiological role of platelet-activating factor in human diseases. Klin Wochenschr 66:373–378.
Laurindo FRM, Goldstein RE, Davenport NJ, et al. (1989) Mechanism of hypotension produced by platelet-activating factor. J Appl Physiol 66:2681–2690.
Lee TC, Lenihan J, Malone B, et al. (1984) Increased biosynthesis of platelet-activating factor in activated human eosinophils. J Biol Chem 259:5526–5530.
Lefer AM, Mueller HF, Smith JB (1984) Pathophysiological mechanisms of sudden death induced by platelet-activating factor. Br J Pharmacol 83:125–130.
Lepran I, Lefer AM (1985) Ischemia-aggravating effect of platelet-activating factor in acute myocardial ischemia. Basic Res Cardiol 80:135–141.
Lindsberg PJ, Yue TL, Frerichs FW, et al. (1990) Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits. Stroke 21:1452–1457.
López-Farre A, Bernabeu F, Gomez-Garre D, et al. (1990) Platelet-activating factor antagonist treatment protects against post-ischemic acute renal failure in rats. J Pharmacol Exp Ther 253:328–333.
Ludwig JC, Hoppens CL, McManus LM, et al. (1985) Modulation of platelet-activating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMN): Role of extracellular albumin. Arch Biochem Biophys 241:337–347.
Mehta J, Wargovich T, Nichols W (1986) Biphasic effects of platelet-activating factor on coronary blood flow in anesthetized dog. Prostaglandins Leukotrienes Med 21:87–95.
Mehta JL, Nichols WW, Mehta P (1988) Neutrophils as potential participants in acute myocardial ischemia: Relevance to reperfusion. J Am Cell Cardiol 12:1309–1316.
Mencia-Huerta JM, Benveniste J (1979) Platelet-activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes. Eur J Immunol 9:409–415.
Mencia-Huerta JM, Lewis RA, Razin E, et al. (1983) Antigen—initiated release of platelet-activating factor (PAF-acether) from mouse bone marrow-derived mast cells sensitized with monoclonal IgE. Immunology 131:2958–2964.
Montrucchio G, Alloatti G, Tetta C, et al. (1985) Release of platelet-activating factor (PAF) from ischemic-reperfused rabbit heart. Am J Physiol 256:H1236-H1246.
Montrucchio G, Camussi G, Tetta C, et al. (1986) Intravascular release of platelet-activating factor during atrial pacing. Lancet 2:293.
Morley J, Page CP, Paul W (1983) Inflammatory actions of platelet-activating factor (PAF-acether) in guinea pig skin. Br J Pharmacol 80:503–509.
Piper PG, Stewart AG (1987) Antagonism of vasoconstriction induced by platelet-activating factor in guinea-pig perfused hearts by selective platelet-activating factor receptor antagonists. Br J Pharmacol 90:771–783.
Prasad K, O'Neil CL, Bharadwaj B (1984) Effects of chronic digoxin treatment on cardiac function, electrolytes, and sarcolemmal ATPase in the canine failing heart due to chronic mitral regurgitation. Am Heart J 108:1487–1494.
Prasad K, Bharadwaj B (1987) Influence of diltiazem on cardiac function at organ and molecular level during hypothermic cardiac arrest. Can J Cardiol 3:351–366.
Prasad K, Kalra J, Chan WP, et al. (1989) Effect of oxygen free radicals on cardiovascular function at organ and cellular levels. Am Heart J 117:1196–1202.
Prasad K, Kalra J, Chaudhary AK, et al. (1990) Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters. Am Heart J 119:538–550.
Prasad K, Chaudhary AK, Kalra J, et al. (1991) Oxygen-derived free radical-producing activity and survival of activated polymorpho-nuclear leukocytes. Mol Cell Biochem 103:51–62.
Prasad K, Bharadwaj B, Kalra J, et al. (1992) Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. Am Heart J 123:37–45.
Rowe GT, Manson NH, Caplan M, et al. (1983) Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Circ Res 53:584–591.
Sacks T, Moldow CF, Craddock PR, et al. (1978) Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes: An in vitro model of immune vascular damage. J Clin Invest 61:1161–1167.
Saeki S, Masugi F, Ogihara T, et al. (1985) Effects of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) on cardiac function in perfused guinea pig heart. Life Sci 37:325–329.
Shaw JOR, Pinckard SF, Ferrigni S, et al. (1981) Activation of human neutrophils with 1-0-hexadecyl/octadecyl-2-acetyl-snglyceryl-3-phosphorylcholine (platelet-activating factor). J Immunol 127:1250–1255.
Smith RJ, Bowman BJ, Iolen SS (1984) Stimulation of the human neutrophil superoxide anion-generating system with 1-0-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphoryl-choline. Biochem Pharmacol 33:973–978.
Turner-Gomes SO, Andrew M, Coles J, et al. (1992) Abnormalities in von Willebrand factor and antithrombin III after cardiopulmonary bypass operations for congenital heart disease. J Thorac Cardiovasc Surg 103:87–97.
Vanden-Bosch H (1980) Intracellular phospholipases A. Biochim Biophys Acta 604:191–246.
Vercellotti GM, Yin HQ, Gustafson KS, et al. (1988) Platelet-activating factor primes neutrophil responses to antagonists: Role in promoting neutrophil-mediating endothelial damage. Blood 71:1100–1107.
Wagner DK, Collins-Lech C, Sohnle PG (1986) Inhibition of neutrophil killing ofCandida albicans pseudohyphae by substances which quench hypochlorous acid and chloramines. Infect Immun 51:731–735.
Warren JS, Mandel DM, Johnson KJ, et al. (1989) Evidence for the role of platelet-activating factor in immune complex vasculitis in the rat. J Clin Invest 83:669–678.
Westgard JO, Lahmeyer BL, Birnbaum ML (1972) Use of the DuPont “Automatic Clinical Analyser” in direct determination of lactic acid in plasma stabilized with sodium fluoride. Clin Chem 18:1334–1338.
Whatley RE, Nelson P, Zimmerman GA, et al. (1989) Regulation of platelet-activating factor production in endothelial cells. J Biol Chem 264:6325–6333.
Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15:212–216.
Yang SS, Bentivoglio LG, Maranhao V, et al. (1972) From Cardiac Catheterization Data to Hemodynamic Parameters. FA Davis: Philadelphia, pp 157–221.
Author information
Authors and Affiliations
About this article
Cite this article
Prasad, K., Gupta, J.B. & Kalra, J. Effects of platelet-activating factor on cardiovascular function, oxygen free radical status, and blood chemistry. International Journal of Angiology 3, 1–11 (1994). https://doi.org/10.1007/BF02014905
Issue Date:
DOI: https://doi.org/10.1007/BF02014905