José Manoel Tannus FilhoI; João José CarneiroI; Carlos Eli PiccinatoI; Walter Villela Andrade VicenteI; Alfredo José RodriguesI; Solange BassetoI; Albert Amin SaderI
RESUMOPentoxifilina (Trental®), vasodilatador com ação reológica, foi administrada a valvopatas adquiridos (7 pacientes - 2 reoperações), antes (1.200mg v.o./dia/3 dias) e durante a operação (1 mg/kg/90 min e.v.) a fim de avaliar seus efeitos sobre as plaquetas e hemodinâmica (grupo pentoxifilina - GP) Oxigenadores de bolhas, hipotermia moderada e cardioplegia sangüínea, fria, intermitente foram usados. Hematócrito, hemoglobina, número de plaquetas e índice de agregados plaquetários circulantes, perdas sangüíneas, volume de transfusões e débito cardíaco, entre outras variáveis, foram seguidos até a 12º hora do p.o.. Os resultados foram comparados com os de um grupo controle (GC) (6 pacientes -1 reoperação) através de testes não paramétricos de Wilcoxon e Mann Whytnei). A pentoxifilina, protegendo as plaquetas, determinou melhores condições de coagulação e menor sangramento p.o. Entretanto, seu efeito vasodilatador foi reduzido ou nulo, sem nenhum benefício para a circulação periférica, resistência vascular sistêmica e débito cardíaco.
ABSTRACTPentoxifylline (Trental ®), vasodilator with rheologic action, was administered to patients with acquired valvopathies (7 pt - 2 reoperations) before (1,200 mg p/day/3 days) and during the surgery (1 mg/kg/90 min, i.v.) to evaluate its effects on the platelets and hemodynamic. Bubble oxygenators, moderate hypothermia and intermittent cold blood cardioplegia were used. Hematocrit, hemoglobin, circulating platelets and aggregate platelets index, blood loss and transfusion and cardiac output were followed among other variables till the 12th post-op. hour. They were compared with a control group (6 pt - 1 reoperation) by non parametric tests of Wilcoxon and Mann Whitney. Pentoxifylline, protecting the platelets, has determined better conditions of coagulation and small post-op bleeding. However, its vasodilator effect was reduced or absent, without any benefit on the periferic circulation, systemic vascular resistance and cardiac output.
1. Blomback M. Noren I, Senning A - Coagulation disturbances during extracorporeal circulation and the post-operative period. Acta Chir Scand 1964; 127: 433-9
2. Bick R L - Alterations of hemostasis associated with cardiopulmonary bypass: pathophysiology, prevention, diagnosis and management. Semin Thromb Hemost 1976; 3: 59-82. [MedLine]
3. Dietzman R H. Ersek R A, Lillehei C W, Castaneda A R, Lillehei R C - Low output syndrome: recognition and treatment. J Thorac Cardiovasc Surg 1969; 57: 138-50. [MedLine]
4. Matthews H R. Meade J B, Evans C C - Significance of prolonged peripheral vasoconstriction after open-heart surgery. Thorax 1974; 29: 343-8. [MedLine]
5. Friedemberg W R, Myers W O. Beathard J, Kummer D J, Sautter R D - Platelet dysfunction associated with cardiopulmonary bypass. Ann Thorac Surg 1978; 25: 298-305. [MedLine]
6. Harker L A, Malpass T E, Bronson H E, Hessel E, Slicheter S J - Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective granule release. Blood 1980; 56: 824-34. [MedLine]
7. Dutton R C, Edmunds Junior L H, Hutchinson J C, Roe B B - Platelet aggregate emboli produced in patient during cardiopulmonary bypass with membrane and bubble oxygenators. J Thorac Cardiovasc Surg 1974; 67: 258-65. [MedLine]
8. De Leval M R, Hill J D, Mielke C H, Macur M F, Gerbode F - Blood platelets and extracorporeal circulation: kinetic studies on dogs on cardiopulmonary bypass. J Thorac Cardiovasc Surg 1975; 69: 144-50.
9. Gomes M M & Mc Goon D C - Bleeding patterns after open-heart surgery. J Thorac Cardiovasc Surg 1970; 60: 87-97. [MedLine]
10. Sanger P W, Robicsek F, Taylor F, Rees T T, Stan R E - Vasomotor regulation during extracorporeal circulation and open-heart surgery. J Thorac Cardiovasc Surg 1960; 40: 355-71.
11. Gordon R J, Ravin M, Daicoff G R - Changes in arterial pressure, viscosity and resistance during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1975; 69: 552-61. [MedLine]
12. Stinson E B, Holloway E L, Derby G C, Copeland J G, Beulher D L, Griepp B R - Control of myocardial performance early after open-heart operations by vasodilator treatment. J Thorac Cardiovasc Surg 1977; 73: 523-59.
13. Nuutinen L S, Pihlajaniemi R, Saarela E, Karkola P, Hollmen A - The effect of dipyridamole on the thrombocyte count and bleeding tendency in open-heart surgery. J Thorac Cardiovasc Surg 1977; 74: 295-301.
14. Kevin H T, Christakis G T, Weisel R D et al. - Dipyridamole preserved platelets and reduced blood after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1988; 96: 332-41. [MedLine]
15. Aren C, Pedersen K, Radegran K - Effects of prostacyclin on platelet activation and postoperative blood loss in coronary bypass. Ann Thorac Surg 1983; 36: 49-54. [MedLine]
16. Brecher G & Cronkite E - Morphology and enumeration of blood platelets, J Appl Physiol 1950; 3: 365-77. [MedLine]
17. Wu K K & Hoak J C A - A new method for the quantitative detection of platelets aggregates in the patients with arterial insufficiency. Lancet 1974; 19: 924-6.
18. Duke W W - The relation of blood platelets to hemorrhagic disease: description of a method for determining the bleeding time and coagulation time and a report of three cases of hemorhagic disease relieved by transfusion. JAMA 1910; 14: 1185-9.
19. Gans W & Swan H J - Measurement of blood by thermodilution. Am J Cardiol 1972; 29: 241 -6. [MedLine]
20. Müller R & Lehrach F - Haemorrheological and cerebrovascular disease: multifunctional approach with pentoxifylline. Current Med Res Opin 1981; 7:253-63.
21. Nishio T, Toshima Y, Matsumo Y - Effects of pentoxifylline on cell shape, ATP content and deformability in rabbit erythrocytes under hyperosmolar conditions. Int J Biochem 1982; 14: 915-20. [MedLine]
22. Schneider R, Schmid-Schoenbeiw H, Kieseweitter H - The reological efficiency of parenteral pentoxifylline (T R) in patients with ischemic brain lesion. Eur Neurol 1983; 22: (Suppl.1) 98-104. [MedLine]
23. Nenci G G - Effect of pentoxifylline on platelet aggregation. Pharmatherapeutica 1981; 2: 532-8. [MedLine]
24. Ekeström S, Liljeqvist L, Nordhus O - Central haemodynamics and coronary arterial blood flow after administration of pentoxifylline to patients with coronary artery disease. Methods Clin Pharmacol 1978; 3: 233-8.
25. Nordhus O, Ekeström S, Liljeqvist L - Effects of pentoxifylline on central hemodynamics in patients with congestive heart failure. Scand J Thorac Cardiovasc Surg 1986; 20: 217-20. [MedLine]
26. Oropello J M, Amin D, Klapholtz A et al. - Effects of pentoxifylline on hemodynamics, oxygen transport, and tissue metabolism in experimental severe hemorrhagic shock. Crit Care Med 1991; 19: 1540-4. [MedLine]
27. Suren A, Bauer F R, Rosekranz B, Bircher J - Effect of pentoxifylline on liver plasma flow in normal man. J Clin Pharmacol 1991; 41: 233-7.
28. Sakurai M L & Komarek J - Comparative studies of 3,7 dimethyl-1-(5-oxo-hexyl) xantine and theophylline on cardiac function. Arch Int Pharmacodyn Ther 1974; 209: 342-8. [MedLine]
29. Watanabe H, Furukawa Y, Chiba S - Cardiovascular effects of aminophylline and pentoxifylline on intact dogs and isolated dog atria. Jap Heart J 1982; 23: 235-43.
30. Zuhdi N, Carey J, Greer A E - Hemodilution and coagulation factors in extracorporeal circulation. J Thorac Cardiovasc Surg 1962; 43: 816-21.
31. Bachmann F, Mc Kenna R, Cole E R, Najafi H - The hemostatic mechanism after open-heart surgery: I. Studies on plasma factors and fibrinolysis in 512 patients after extracorporeal circulation. J Thorac Cardiovasc Surg 1975; 70: 76-82.
32. Mohr R, Golan M, Rosner E, Goor D, Ramot B - Effect of cardiac on pletelets. J Thorac Cardiovasc Surg 1968; 92: 715-59.
33. Mezzano D, Habash J, Aranda E et al. - Thrombocytopenia and platelet dysfunction during and after surgery with extracorporeal circulation. Sangre 1986; 31: 425-34. [MedLine]
34. Perkins H, Osborn J J, Gerbode F - Management of abnormal bleeding following extracorporeal circulation. Ann Intern Med 1959; 51: 658-67. [MedLine]
35. Gibbon Junior J H & Camishion R C - Problems in hemostasis associated with extracorporeal circulation. Ann New York Acad Sci 1964; 115: 195-8.
36. Garcia J B, Pakrashi B C, Mary D A, Tandon R K, lonescu M I - Postoperative blood loss after extracorporeal circulation for heart valve surgery. J Thorac Cardiovasc Surg 1973; 65: 487-95.
37. Zucker M B & Borelli J - Viscous metamorphosis produced by chilling and by clotting. Failure to find specific defect of viscous metamorphosis in PTA sydrome. Thromb Diath Haemorhagy 1960; 4: 425-32.
38. Heidrich H, Paeprer M, Barcow D, Schartl M - The effect of pentoxifylline on central and peripheral haemodynamic: an experimental study. Z Kardiol 1976; 65: 385-91. [MedLine]
39. Kouchoukos N T, Sheppard L C, Kirklin J W - Effect of alterations in arterial pressure on cardiac performance early after open intracardiac operations. J Thorac Cardiovasc Surg 1972; 64: 563-9.
40. Matthews H R, Meade J B, Evans C C - Peripheral vasoconstriction after open-heart sugery. Thorax 1974; 29: 338-42. [MedLine]