A Study of Platelet Activation during Human Cardiopulmonary Bypass and the Effect of S-Nitrosoglutathione

Summary

Cardiac surgery is complicated by the occurrence of post-operative bleeding due to platelet dysfunction. This is largely caused by platelet activation and consumption during cardiopulmonary bypass. Patients undergoing cardiac surgery requiring cardiopulmonary bypass were studied to determine whether early platelet changes due to bypass could be inhibited using the platelet-selective nitric oxide donor S-nitroso-glutathione (GSNO). Flow cytometry was used to measure platelet surface expression of P-selectin (an α-granule protein) and glycoproteins (GP) IIb/IIIa and Ib (mediators of aggregation and adhesion) before and 5 and 10 min after commencing cardiopulmonary bypass, in 6 controls and 6 patients receiving GSNO 50 μg/min. Platelet P-selectin expression increased during bypass both in controls and patients receiving GSNO. Glycoproteins IIb/IIIa and Ib fell during bypass in control and GSNO-treated patients. There was no difference between control and GSNO-treated groups. Thus no significant platelet inhibition by S-nitrosoglutathione was demonstrated under these conditions.

• References

• 1 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 76: 1680-1697
• 2 Harker LA, Malpass TW, Branson HE, Hessel EA, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective α-granule release. Blood 1980; 56: 824-834
• 3 Ray MJ, Hawson GA, Just SJ, McLachlan G, O’Brien M. Relationship of platelet aggregation to bleeding after cardiopulmonary bypass. Ann Thorac Surg 1994; 57: 981-986
• 4 Zilla P, Fasol R, Groscurth P, Klepetko W. Blood platelets in cardiopulmonary bypass operations. J Thorac Cardiovasc Surg 1989; 97: 379-388
• 5 Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault K, Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anaesthesiology 1991; 75: 388-393
• 6 George JN, Pickett EB, Saucerman S, McEver RP, Kunicki TJ. Platelet surface glycoproteins studies on resting and activated platelets and platelet membrane microparticles in normal subjects and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest 1986; 78: 340-348
• 7 Radomski MW, Palmer RMJ, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987; 02: 1057-1058
• 8 Radomski MW, Palmer RMJ, Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 1990; 87: 5193-5197
• 9 Radomski MW, Rees DD, Dutra A, Moncada S. S-nitrosoglutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol 1992; 107: 745-759
• 10 de Beider AJ, MacAllister R, Radomski MW, Moncada S, Vallance PJT. Effects of S-nitroso-glutathione in the human forearm circulation: evidence for selective inhibition of platelet activation. Cardiovasc Res 1994; 28: 691-694
• 11 Langford EJ, Wainwright RJ, Martin JF. Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors. Arterioscler Thromb Vasc Biol 1996; 16: 51-55
• 12 Tabuchi N, Tigchelaar I, van-Oeveren W. Shear-induced pathway of platelet function in cardiac surgery. Semin Thromb Hemost 1995; (Suppl. 21) 2: 66-70
• 13 Cramer EM, Lu H, Soria C, Bemdt MC, Tenza D. Differential redistribution of platelet glycoproteins Ib and IIb/IIIa after plasmin stimulation. Blood 1991; 77: 694-699
• 14 Hourdille P, Heilmann E, Combrie R, Winkler J, Clemetson KJ, Nurden AT. Thrombin induces a rapid redistribution of glycoprotein Ib-IX complexes within the membrane systems of activated human platelets. Blood 1990; 76: 1503-1513
• 15 Mazer CD, Homstein A, Freedman J. Platelet activation in warm and cold heart surgery. Ann Thorac Surg 1995; 59: 1481-1486
• 16 Khuri SF, Valeri CR, Loscalzo J, Weinstein MJ, Biijiniuk V, Healey NA, MacGregor H, Doursounian M, Zolkewitz MA. Heparin causes platelet dysfunction and induces fibrinolysis before cardiopulmonary bypass. Ann Thorac Surg 1995; 60: 1008-1014
• 17 Wahba A, Black G, Koksch M, Rothe G, Preuner J, Schmitz G, Bimbaum DE. Aprotinin has no effect on platelet activation and adhesion during cardiopulmonary bypass. Thromb Haemost 1996; 75: 844-848
• 18 Uthoff K, Zehr KJ, Geerling R, Herskowitz A, Cameron DE, Reitz BA. Inhibition of platelet adhesion during cardiopulmonary bypass reduces postoperative bleeding. Circulation 1994; 90 [part 2] II269-II274
• 19 Bemabei A, Gikakis N, Kowalska MA, Niewiarowski S, Edmunds LH. Iloprost and echistatin protect platelets during simulated extracorporeal circulation. Ann Thorac Surg 1995; 59: 149-153
• 20 Muikku O, Kuitunen A, Hynynen M. Effects of organic nitrate vasodilators on platelet function before and after cardiopulmonary bypass. Acta Anaesthesiol Scand 1995; 39: 618-623
• 21 Ramsey B, Radomski MW, de Beider A, Martin JF, Lopez-Jaramillo P. Systemic effects of S-nitroso-glutathione in the human following intravenous infusion. Br J Clin Pharmacol 1995; 40: 101-102
• 22 Lees C, Langford E, Brown A, de Beider A, Martin JF, Pickles A, Campbell S. The effects of S-nitrosoglutathione on platelet activation hypertension and uterine and fetal Dopplers in severe pre-eclampsia. Obstet Gynecol 1996; 88: 14-19
• 23 Malmros C, Blomquist S, Dahm P, Martensson L, Thome J. Nitric oxide inhalation decreases pulmonary platelet and neutrophil sequestration during extracorporeal circulation in the pig. Crit Care Med 1996; 24: 845-849
• 24 Sly MK, Prager MD, Eberhart RC, Jessen ME, Kulkarni PV. Inhibition of surface-induced platelet activation by nitric oxide. ASAIO-J 1995; 41: M394-M398