Advertisement
Paper| Volume 48, ISSUE 5, P519-533, December 01, 1987

Effects of antiplatelet drugs on pulmonary responses to thrombin in anesthetized rabbits

DOI:https://doi.org/10.1016/0049-3848(87)90384-7
Effects of antiplatelet drugs on pulmonary responses to thrombin in anesthetized rabbits
Previous ArticleAn extract of feverfew inhibits interactions of human platelets with collagen substrates
Next ArticleImpaired thromboxane synthesis in preactivated human blood platelets: Agonist-specific, irreversible desensitization to thrombin
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Platelet aggregation and fibrin deposition in the pulmonary circulation may contribute to the pathogenesis of lung injury in the adult respiratory distress syndrome (ARDS). We evaluated the effect of two antiplatelet drugs (forskolin& dipyridamole) on pulmonary responses to intravenous infusion of 100 NIH units of thrombin per kg bw in anesthetized, and ventilated rabbits treated with fibrinolysis inhibitor. Thrombin infusion resulted in pulmonary hypertension and increased arterial C02 tension (PaCO2) and dead space ventilation (VD/VT). Arterial oxygen tension (PaO2) and numbers of circulating leukocytes and platelets dropped after thrombin infusion. These early hemodynamic changes correlated with histological evidence of entrapped leukocytes in the pulmonary microcirculation and transient alveolar edema. Microthrombi were rarely observed in animals that received thrombin. There was little evidence for endothelial damage or progressive lung water accumulation. Treatment with forskolin or dipyridamolereversed thrombin-induced changes in pulmonary artery pressure, PaC02, VD/VT and systemic oxygenation. Moreover, forskolin and dipyridamole blunted the drop in circulating leukocytes and prevented the development of alveolar edema following thrombin. The beneficial actions of these agents may be due to interference with the release of mediators from leukocytes or platelets.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Thrombosis Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Murray J.F.
        Mechanisms of acute respiratory failure.
        in: NHBLI Conference Report. Statistics, 1982 Edition. Am. Rev. Res. Dir. Dis.115. 1977: 1071-1078
        • Hill J.D.
        • Rattliff J.L.
        • Pahrott J.C.W.
        • Lamy M.
        • Fallat J.
        • Koeniger E.
        • Yaeger E.M.
        • Whitmer G.
        Pulmonary pathology in acute respiratory insufficiency.
        J. Thor. Cardiovasc. Surg. 1976; 71: 64-71
        • Blaisdel F.W.
        Pathophysiology of the respiratory distress syndrome.
        Arch. Surg. 1974; 108: 44-49
        • Greene R.
        • O'Connell R.S.
        • Snow R.
        • Snider M.
        • Zapol W.
        • Reid L.
        Bedside balloon occlusion angiography in acute respiratory failure.
        Am. Rev. Respir. Dis. 1980; 121: 143-148
        • Malik A.B.
        • Johnson A.
        • Tahamont M.V.
        Mechanisms of lung vascular injury after intravascular coagulation.
        Ann. N.Y. Acad. Sci. 1982; 385: 213-234
        • Saldeen T.
        The microembolism syndrome.
        Microvasc. Res. 1976; 11: 27-259
        • Malik A.B.
        Pulmonary microembolism.
        Physiol. Rev. 1983; 63: 1114-1207
        • Rowland F.N.
        • Donovan M.J.
        • Picciano P.T.
        • Wilner G.D.
        • Kreutzer D.L.
        Fibrin-mediated vascular injury: indentification of fibrin peptides that mediate endothelial injury.
        Am. J. Path. 1984; 117: 418-428
        • Saldeen T.
        Fibrin-derived peptides and pulmonary injury.
        Ann. N.Y. Acad Sci. 1982; 584: 319-331
        • Luterman A.
        • Manwaring D.
        • Curreri P.W.
        The role of fibrinogen degradation products in the pathogenesis of the respiratory distress syndrome.
        Surgery. 1977; 82: 703-709
        • Lindquist O.
        • Rammer L.
        • Saldeen T.
        Pulmonary insufficiency, microembolism and fibrinolysis inhibition in post-traumatic autopsy material.
        Acta Chirq. Scand. 1972; 138: 545-549
        • Lo S.K.
        • Perlman M.B.
        • Neihaus G.H.
        • Malik A.B.
        Thrombin-induced alterations in lung fluid balance in awake sheep.
        J. Appl. Physiol. 1985; 58: 1421-1427
        • Arfors K.E.
        • Busch C.
        • Jakobson S.
        • Lindquist O.
        • Malmberg P.
        • Rammer L.
        • Saldeen T.
        Intravascular infusion of thrombin and tranexamic acid in the dog.
        Acta Chira. Scand. 1972; 138: 445-452
        • Johnson A.
        • Tahamont M.V.
        • Malik A.B.
        Thrombininduced lung vascualr injury: Role of fibrinogen and fibrinolysis.
        Am. Rev. Resp. Dis. 1983; 128: 38-44
        • Hasan F.M.
        • Teplitz C.
        • Farrugia R.
        • Huan E.
        • Schwartz S.
        Lung function and structure after Escherichia coli endotoxin in rabbits: Effect of dose and rate of administration.
        Circ. Shock. 1984; 13: 1-19
      16. Dixon W.J. BMDP Statistical Software. University of California Press, Berkley CA1983
        • Gerdin B.
        • Diffang C.
        • Saldeen T.
        Pulmonary insufficiency in the rat after intravascular coagulation and inhibition of fibrinolysis.
        Europ. Surg. Res. 1981; 13: 402-413
        • Binder A.S.
        • Kageler W.
        • Perel A.
        • Flick M.R.
        • Staub N.C.
        Effect of platelet depletion on lung vascular permeability after microemboli in sheep.
        J. Appl. Physiol. 1980; 48: 414-420
        • Severinghaus J.W.
        • Stupfel M.A.
        Alveolar dead space as an index of distribution of blood flow in pulmonary capillaries.
        J. Appl. Physiol. 1957; 10: 335-348
        • Vaage J.
        Intravascular platelet aggregation and acute respiratory insufficiency.
        Circ. Shock. 1980; 4: 279-290
        • Nadel J.A.
        • Colebatch H.J.H.
        • Olsen C.R.
        Location and mechanism of airway constriction after barium sulfate microembolization.
        J. Appl. Physiol. 1965; 20: 164-167
        • De Souza N.J.
        • Dohadwalla A.N.
        • Reden J.
        Forskolin: A labdane diterpene with inotropic, platelet aggregation inhibitory and adenylate cyclase activiating properties.
        Medicinal Res. Rev. 1983; 3: 201-219
        • Agarwal K.C.
        • Parks Jr., R.E.
        Synergistic inhibition of platelet aggregation by forskolin plus PGE1 or 2-fluoroadenosine.
        Biochem. Pharmacol. 1982; 31: 3713-3716
        • Berne R.M.
        • Winn H.R.
        • Knabb R.M.
        • Ely S.W.
        • Rubio R.
        Blood flow regulation by adenosine in heart, brain and skeletal muscle.
        in: Berne R.M. Rall T.W. Rubio R. Regulatory Function of Adenosine. Martins Nijhoff Publishers, Boston1983: 347-360
        • Dawicki D.D.
        • Agarwal K.C.
        • Parks Jr., R.E.
        Role of adenosine uptake and metabolism by blood cells in the antiplatelet actions of dipyridamole, dilazep and nitrobenzylthioionosine.
        Biochem. Pharmacol. 1985; 34: 3965-3972
        • Sollevi A.
        • Ostergren J.
        • Hjemdahl P.
        • Fredholm B.
        • Fargrell B.
        The effect of dipyridamole on plasma adenosine levels and skin microcirculation in man.
        J. Clin. Chem. Clin. Biochem. 1982; 20: 420-421
        • Plow E.F.
        Leukocyte elastase release during blood coagulation.
        J. Clin. Invest. 1982; 69: 564-572
        • Lava J.S.
        • Rice C.L.
        • Levine H.A.
        • Moss G.S.
        Extravascular lung water as a function of pulmonary artery pressure in the septic pig.
        J. Surg. Res. 1982; 322: 440-448

      Article info

      Publication history

      Accepted: September 28, 1987
      Received: May 22, 1987

      Identification

      DOI: https://doi.org/10.1016/0049-3848(87)90384-7

      Copyright

      © 1987 Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX