RSS-Feed abonnieren
DOI: 10.1055/s-0037-1615139
Platelet Activation and Cytokine Production during Hypothermic Cardiopulmonary Bypass – A Possible Correlation?
Publikationsverlauf
Received
03. Juni 1997
Accepted after resubmission
09. März 1998
Publikationsdatum:
08. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199801/lookinside/thumbnails/10-1055-s-0037-1615139-1.jpg)
Summary
Cardiopulmonary bypass (CPB) is associated with impaired platelet function and a systemic inflammatory response. The present study was designed to evaluate whether any correlation between platelet activation and inflammatory response during CPB exists. The results obtained from 8 patients undergoing hypothermic CPB for cardiac surgery showed the occurrence of a moderate degree of platelet activation during CPB, demonstrated by an increase of platelet CD62P expression in correlation with an increase of β-thromboglobulin levels, with a concomitant decrease of in vitro platelet response. Plasma IL-1β levels significantly increased during CPB, with a peak between 1 and 4 h after CPB. Similarly, IL-6 levels were elevated 30 min from CPB starting, peaked at 4 h, and remained elevated after 24 h. A direct correlation was found between plasma IL-1β and IL-6 levels. A significant correlation between plasma IL-1β and β-thromboglobulin levels was also found. In turn, plasma β-thromboglobulin levels correlated with CD62P expression on activated platelets. An inverse correlation was found between in vitro platelet aggregation and plasma IL-1β or IL-6 levels. From the present results it may be speculated that platelet activation during CPB may contribute, through the release of IL-1β, to activation of endothelial cells and subsequent release of other cytokines with chemotactic and pro-inflammatory properties, thus playing an important role in the inflammatory response associated with CPB.
-
References
- 1 Harker LA, Malpass TW, Branson HE, Hessel EA II, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release.. Blood 1980; 56: 824-34.
- 2 Bick RL. Hemostasis defects associated with cardiac surgery, prosthetic devices, and other extracorporeal circuits.. Semin Thromb Hemost 1985; 11: 249-80.
- 3 Woodman RC, Harker LA. Bleeding complications associated with cardio-pulmonary bypass.. Blood 1990; 76: 1680-97.
- 4 Khuri SF, Wolfe JA, Josa M, Axford TC, Szymanski I, Assousa S, Ragno G, Patel M, Silverman A, Park M, Valeri R. Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and non surgical blood loss.. J Thorac Cardiovasc Surg 1992; 104: 94-107.
- 5 Menichetti A, Tritapepe L, Ruvolo G, Speziale G, Cogliati A, Di Giovanni C, Pacilli M, Criniti A. Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: aprotinin vs. tranexanic acid vs. epsilon aminocaproic acid.. J Cardiovasc Surg 1996; 37: 401-7.
- 6 Rinder CS, Mathew JP, Rinder HM, Bonan J, Ault KA, Smith BR. Modulation of platelet surface adhesion receptors during cardiopulmonary bypass.. Anesthesiology 1991; 75: 563-70.
- 7 Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault KA, Hillmann R. Platelet activation and aggregation during cardiopulmonary bypass.. Anesthesiology 1991; 75: 388-93.
- 8 Komai H, Haworth SG. Effect of cardiopulmonary bypass on the circulating level of soluble GMP-140.. Ann Thorac Surg 1994; 58: 478-82.
- 9 Mazer CD, Hornstein A, Freedman J. Platelet activation in warm and cold heart surgery.. Ann Thorac Surg 1995; 59: 1481-6.
- 10 Ferraris VA, Rodriguez E, Ferraris SP, Huang M, Gupta A, Bennet JA, Andersen TA, Dunn H, Fenton II JW, Smith B. Platelet aggregation abnormalities after cardiopulmonary bypass (Letter).. Blood 1994; 83: 299-300.
- 11 Boldt J, Knothe C, Welters I, Dapper FL, Hempelmann G. Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?. Ann Thorac Surg 1996; 62: 130-5.
- 12 Kestin AS, Valeri CR, Khuri SF, Loscalzo J, Ellis PA, MacGregor H, Birjiniuk V, Ouimet H, Pasche B, Nelson MJ, Benoit SE, Rodino LJ, Barnard MR, Michelson AD. The platelet function defect of cardiopulmo-nary bypass.. Blood 1993; 82: 107-17.
- 13 Markewitz A, Faist E, Lang S, Endres S, Hultner L, Reichart B. Regulation of acute phase response after cardiopulmonary bypass by immunomodulation.. Ann Thorac Surg 1993; 55: 389-94.
- 14 Casey LC. Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure.. Ann Thorac Surg 1993; 56: S92-6.
- 15 Frering B, Philip I, Dehoux M, Rolland C, Langlois JM, Desmonts JM. Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass.. J Thorac Cardiovasc Surg 1994; 108: 636-41.
- 16 Menasche P, Haydar S, Peynet J, Du Buit C, Merval R, Bloch G, Piwnica A, Tedgui A. A potential mechanism of vasodilatation after warm heart surgery. The temperature-dependent release of cytokines.. J Thorac Cardiovasc Surg 1994; 107: 293-9.
- 17 Saatvedt K, Lindberg H, Geiran OR, Michelsen S, Aasen AO Pedersen T, Mollnes TE. Complement activation and release of tumor necrosis factor alpha, interleukin-2, interleukin-6 and soluble tumor necrosis factor and interleukin-2 receptors during and after cardiopulmonary bypass in children.. Scand J Clin Lab Invest 1995; 55: 79-86.
- 18 Marti F, Munoz J, Peiro M, Bertran E, Ferran C, Octavio C, Garcia J, Rueda F. Higher cytotoxic activity and increased levels of IL-1 beta and TNF-alpha in patients undergoing cardiopulmonary bypass.. Am J Hematol 1995; 49: 237-9.
- 19 Deng MC, Wiedner M, Erren M, Mollhoff T, Assmann G, Scheld HH. Arterial and venous cytokine response to cardiopulmonary bypass for low risk CABG and relation to hemodynamics.. Eur J Cardiothorac Surg 1995; 9: 22-9.
- 20 Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliott M. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass.. J Thorac Cardiovasc Surg 1993; 105: 234-41.
- 21 Jorens PG, De Jongh R, Backer W, Van Damme J, Van Overveld F, Bossaert L, Walter P, Herman AG, Rampart M. Interleukin-8 production in patients undergoing cardiopulmonary bypass. The influence of pretreatment with methylprednisolone.. Am Rev Respir Dis 1993; 148: 890-5.
- 22 Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, Leung JM, Mangano DT, Greenfield LJ, Rankin JS. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization.. J Thorac Cardiovasc Surg 1994; 108: 626-36.
- 23 Kishimoto T. The biology of interleukin-6.. Blood 1989; 74: 1-10.
- 24 Smyth MJ, Ortaldo RJ. Comparison of the effect of interleukin-2 and inter-leukin-6 on lytic activity of purified human peripheral blood large granular lymphocytes.. J Immunol 1990; 146: 1380-4.
- 25 Van Snick J. Interleukin-6: an overview.. Ann Rev Immunol 1990; 8: 253-78.
- 26 Burstein SA. Effects of interleukin-6 on megakaryocytes and on canine platelet function.. Stem Cells Dayt 1994; 12: 386-93.
- 27 Oleksowicz L, Mrowiec Z, Zuckerman D, Isaacs R, Dutcher J, Puszkin E. Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism.. Thromb Haemost 1994; 72: 302-8.
- 28 Hawrylowicz CM, Santoro SA, Platt FM, Unanue ER. Activated platelets express IL-1 activity.. J Immunol 1989; 143: 4015-8.
- 29 Sedlmayr P, Blaschitz A, Wilders-Truschnig M, Tiran A, Dohr G. Platelets contain interleukin-1 alpha and beta which are detectable on the cell surface after activation.. Scand J Immunol 1995; 42: 209-14.
- 30 Hawrylowicz CM, Howells GL, Feldmann M. Platelet-derived inter-leukin-1 induces human endothelial adhesion molecule expression and cytokine production.. J Exp Med 1991; 174: 785-90.
- 31 Kaplanski G, Porat R, Aiura K, Erban JK, Gelfand JA, Dinarello CA. Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event.. Blood 1993; 10: 2492-5.
- 32 Ferroni P, Gazzaniga PP. Evaluation of the clinical utility of platelet aggregation studies in the long-term follow-up of patients with atherosclerotic vascular disease.. J Clin Lab Analysis 1992; 6: 257-63.
- 33 Thavasu PW, Longhurst S, Joel SP, Slevin ML, and Balkwill FR. Measuring cytokine levels in blood. Importance of anticoagulants, processing, and storage conditions.. J Immunol Methods 1992; 153: 115-24.
- 34 Ruvolo G, Greco E, Speziale G, Tritapepe L, Marino B, Mollace V, Nisticò G. Nitric oxide formation during cardiopulmonary bypass.. Ann Thorac Surg 1994; 57: 1055-7.
- 35 Ruvolo G, Speziale G, Greco E, Tritapepe L, Mollace V, Nisticò G, Marino B. Nitric oxide release during hypothermic vs normothermic cardiopulmo-nary bypass.. Eur J Cardiothorac Surg 1995; 9: 651-4.
- 36 Speziale G, Ruvolo G, Marino B. A role for nitric oxide in the vasoplegic syndrome.. J Cardiovasc Surg 1996; 37: 301-3.
- 37 Edmunds Jr LH, Ellison N, Colman RW, Niewiarowski S, Rao AK, Addonizio Jr VP, Stephenson LW, Edie RN. Platelet function during open heart surgery: comparison of membrane and bubble oxygenators.. J Thorac Cardiovasc Surg 1982; 83: 805-12.
- 38 Packham MA, Evan G, Glynn MG, Mustard TF. The effect of plasma proteins in the interaction of platelets with glass surfaces.. J Lab Clin Med 1969; 73: 686-97.
- 39 Vroman L, Adams AL, Fischer GC, Munoz PC. Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces.. Blood 1980; 55: 156-9.
- 40 Gillinov AM, Bator JM, Zehr KJ, Redmond JM, Burch RM, Ko C, Winkelstein JA, Stuart RS, Baumgartner WA, Cameron DE. Neutrophil adhesion expression during cardiopulmonary bypass with bubble and membrane oxygenator.. Ann Thorac Surg 1993; 56: 847-53.
- 41 Valeri CR, Khabbaz K, Khuri SF, Marquardt C, Ragno G, Feingold H, Gray AD, Axford C. Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass.. J Thorac Cardiovasc Surg 1992; 104: 108-16.
- 42 Wengert RK, Lukasiewicz H, Mikuta BS, Niewiarowski S, Edmunds LH. Loss of platelet fibrinogen receptors during clinical cardiopulmonary bypass.. J Thorac Cardiovasc Surg 1989; 97: 235-9.
- 43 Gluszko P, Rucinski B, Musial J, Wegner RK, Schmaier AH, Colman RW, Edmunds Jr LH, Niewiarowski S. Fibrinogen receptors in platelet adhesion to surfaces of extracorporeal circuits.. Am J Physiol 1987; 252: H615-H21.
- 44 Ellison N, Edmunds Jr LH, Colman RW. Platelet aggregation following heparin and protamine administration.. Anesthesiology 1978; 48: 65-8.
- 45 Kennedy PS, Solis RT, Storey Jr SS, Viancos JG, DeBakey ME. Cardiopulmonary bypass surgery. Platelet aggregation during induction of anesthesia and following heparinization of patients.. Arch Surg 1978; 113: 1429-32.
- 46 Dunlop LC, Skinner MP, Bendall LJ, Favaloro EJ, Castaldi PA, Gorman JJ, Gamble JR, Vadas MA, Berndt MC. Characterization of GMP-140 (P-selectin) as a circulating plasma protein.. J Exp Med 1992; 175: 1147-50.
- 47 Jilma B, Eichler HG, Vondrovec B, Breiteneder H, Kyrle PA, Kitzweger E, Kapiotis S, Speiser W. Effects of desmopressin on circulating P-selectin.. Br J Haematol 1996; 93: 432-6.
- 48 Castell JV, Gomez-Lechon MJ, David M, Andus T, Geiger T, Trullenque R, Fabra R, Heinrich PC. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes.. FEBS Letters 1989; 242: 237-9.
- 49 Zhang Z, Fuentes NL, Fuller GM. Characterization of the IL-6 responsive elements in the gamma fibrinogen gene promoter.. J Biol Chem 1995; 270: 24287-91.
- 50 Ferroni P, Basili S, Alessandri C, Vieri M, Martini F, Belogi A, Pulcinelli FM, Cordova C, Gazzaniga PP. Proinflammatory cytokines and haemostatic system in patients with chronic obstructive pulmonary disease.. Platelets 1997; 8: 255-9.