Hemorheological Changes in Elderly Subjects-Effect of Pentosan Polysulfate and Possible Role of Leucocyte Arachidonic Acid Metabolism

Summary

The effects of pentosan polysulfate (PPS) on various hemorheological parameters were studied in a group of very elderly subjects in good general health. Alterations in blood viscosity and filterability were detected in these patients, without any concomitant changes in factors which are known to affect these parameters: notably hematocrit, fibrinogen and plasma lipid levels. The hemorheological abnormalities were considerably improved by twice daily treatment with 50 mg of PPS (i.m.).

Apart from its anticoagulant activity, PPS has been shown to have an anti-inflammatory action. We were interested to investigate its effects on metabolism of exogenous arachidonic acid (AA) by both platelets and leucocytes. It is becoming increasingly recognized that metabolites of AA via the 5 LO pathway appear to play a role in inflammatory processes. In this study, PPS was found to inhibit leucocyte 5 LO activity. Reduction in the levels of these metabolites may therefore have an effect on whole blood rheology.

Keywords

Elderly - Pentosan polysulfate - Hemorheology - Arachidonic acid - Leucotrienes - Leucocyte

• References

• 1 Ciuffetti G, Parnetti L, Senin U. Hemorheological factors in a group of elderly patients with acute mental confusion. Clin Hemorheol 1984; 4: 341-361
• 2 Joffe SN. Drug prevention of post operative deep vein thrombosis. A comparative study of calcium heparinate and sodium pentosane polysulfate. Arch Surg 1976; 111: 37-40
• 3 Reid HL, Barnes JA, Lock PJ, Dormandy JA, Dormandy TL. A simple method for measuring erythrocyte deformability. J Clin Path 1976; 26: 855-858
• 4 Fischer AM, Barrowcliffe TW, Thomas DP. A comparison of pentosan polysulfate (SP54) and heparin. Mechanism of action on blood coagulation. Thromb Haemostas 1982; 47: 104-108
• 5 Freyburger G, Vergnes C, Hourdille P, Boisseau MR, Sanchez R, Cutillas M, Perro G. Etude biologique de l’action du polysulfate de pentosane chez les brûlés graves. Ann Chir 1984; 38: 247-252
• 6 Rijken DC, Juhan-Vague I, De Cock F, Collen D. Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay. J Lab Clin Med 1983; 101: 274-284
• 7 Vanderhoeck JY, Bailey JM. Activation of a 15 Lipoxygenase/ leukotriene pathway in human polymorphonuclear leukocytes by the Anti-Inflammatory Agent Ibuprofen. J Biol Chem 1984; 259: 6752-6756
• 8 Craddock PR, Hammerschmidt D, White JG, Dalmasso AP, Jacob HS. Complement (C5a) induced granulocyte aggregation in vitro. J Clin Invest 1977; 60: 260-264
• 9 Stuart J. The acute phase reaction and hematological stress syndrome in vascular disease. Thromb Res 1980; 17: 831-840
• 10 Thomas DP, Barrowcliffe TW, Merton RE, Stocks J, Dawes J, Pepper DS. In vitro release of anti Xa clotting activity by a heparin analog. Thromb Res 1980; 17: 831-840
• 11 Ehrly AM, Muller HE. Aggregation und Desaggregation von Erythrozyten. Acta Haematol 1966; 36: 323-334
• 12 Goetzl EJ, Pickette WC. Novel structural determinants of the human neutrophil chemotactic activity of leucotriene B. J Exp Med 1981; 153: 482-487
• 13 Smith M JH, Walker JR. The effects of some antirheumatic drugs on an in vitro model of human polymorphonuclear leucocyte chemokinesis. Br J Pharmacol 1980; 69: 473-478
• 14 O’Flaherty JT, Thomas MJ, Lousart SL, Salzer WL, Mc Call CE. Neutropenia induced by systemic infusion of 5-12 dihydroxy-6-8-10-14 eicosatetraenoic acid, correlation with its in in vitro effects upon neutrophils. J Clin Invest 1982; 69: 993-998
• 15 O’Flaherty JT, Showell HJ, Becker EL, Ward PA. Neutrophil aggregation and degranulation. Am J Pathol 1979; 95: 433-444
• 16 Ford-Hutchinson AW, Bray MA, Smith M JH. The aggregation of rat neutrophils by arachidonic acid pathway: a possible bioassay for lipoxygenase activity. J Pharmacol 1979; 31: 868-869
• 17 Chien S. Electrochemical interactions between erythrocyte surfaces. Thromb Res 1976; 8: 189-202
• 18 Bruhn HD. Rheological consequences of fibrinolysis and of anticoagulation. Clin Hemorheol 1984; 4: 29-34
• 19 Laghi-Pasini F, Pasqui AL, Ceccatelli L, Capecchi L, Orrico A, Di Perri T. Heparin inhibition of polymorphonuclear leukocyte activation in vitro. A possible pharmacological approach to granulocytemediated vascular damage. Thromb Res 1984; 35: 527-537