Vasodilatative Prostanoide und pulmonale Strombahn

Zusammenfassung

Die Prostanoide PGE₁ und PGl₂ besitzen eine ausgeprägte vasodilatative Potenz in der pulmonalen Zirkulation. Sie sind prinzipiell in der Lage, vasokonstriktive Stimuli mit präund/oder postkapillärer Lokalisation zu antagonisieren. Sie sind nach intravenöser Applikation jedoch nicht pulmonal selektiv, sondern biologisch wirksame Mengen gelangen auch in die systemische Zirkulation mit resultierender Abnahme des gesamtperipheren Widerstandes. Intravenös zugeführte vasodilatative Prostanoide besitzen zudem keine intrapulmonale Selektivität. Aufgrund ihres Wirkungsprofils und ihrer guten Titrierbarkeit stellen vasodilatative Prostanoide im intensivmedizinischen Bereich dennoch für ausgesuchte Patienten mit kritischer pulmonaler Hypertension und Rechtsherz-Dekompensation ein wertvolles therapeutisches Agens dar. Bei rechtskardialer Dekompensation im Rahmen der primären pulmonalen Hypertonie kann eine ambulante intravenöse Dauerinfusion von PGE₁ oder PGI₂ praktiziert werden, um eine Überbrückung zur (Herz-)Lungentransplantation zu erreichen. Bei Patienten mit ARDS und Sepsis sind vasodilatative Prostanoide mit dem Ziel eingesetzt worden, über eine Steigerung des Sauerstofftransportes und eine Beeinflussung mikrozirkulatorischer Verteilungsstörungen eine Steigerung der Sauerstoffaufnahme und somit der Reduktion der Organkomplikationen zu erreichen. Perspektivisch könnte eine Aerosolapplikation vasodilatativer Prostanoide hilfreich sein, eine pulmonale und intrapulmonale Selektivität der Vasodilatation durch diese Agenzien zu erzielen.

Schlüsselwörter

Vasodilatative Prostanoide - Prostaglandin E₁ und l₂ pulmonale Hypertonie - akutes respiratorisches Distress Syndrom (ARDS) - Sepsis

• Literatur

• 1 Adams DO, Hamilton TA. The call biology of macrophage activation. Ann Rev Immunol 1984; 02: 283-314.
• 2 Appel PL, Shoemaker WC. Hemodynamic and oxygen transport effects of prostaglandin E₁ in patients with adult respiratory distress syndrome. Crit Care Med 1984; 12: 528-9.
• 3 Bakhle YS, Moncada S, de Nucci G, Salmon JA. Differential release of eicosanoids by bradykinin and calcium ionophore A 23187 in guinea-pig isolated perfused lung. Br J Pharmacol 1985; 86: 55-62.
• 4 Barst RJ, Stalcup SA. Endothelial function in clinical pulmonary hypertension. Chest 1985; 88: 216-20.
• 5 Barst RJ. Pharmacologically-induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension. Chest 1986; 89: 497-503.
• 6 Batra AK, Segall PH, Ahmed T. Pulmonary edema with nifedipine in primary pulmonary hypertension. Respiration 1985; 47: 161-3.
• 7 Bihari D, Smithies M, Gimson A, Tinker J. The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 1987; 317: 397-403.
• 8 Bone RC, Slotman G, Maunder R, Silvermann H, Ursprung JJ. Randomized doubleblind, multicenter study of prostaglandin E₁ in patients with the adult respiratory distress syndrome. Chest 1989; 96: 114-9.
• 9 Bugiardini R, Chiercha S, Crea E. Evaluation of the effects of catheter sampling for the study of platelet behaviour in the pulmonary and coronary circulation. Am Heart J 1984; 108: 255-60.
• 10 Burghuber OC, Mathias MM, McMutry IF, Reeves JT, Voelkel NE. Lung edema due to hydrogen peroxide is independent of cyclooxygenase products. J Appl Physiol 1984; 56: 900-5.
• 11 Christman BW, McPherson CD, Newman JH, King GA, Bernard GR, Groves BM, Loyd JE. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992; 327: 70-5.
• 12 Cox JW, Andreadis NA, Bone RC, Maunder RJ, Pullen RH, Ursprung JJ, Vassar MJ. Pulmonary extraction and pharmacokinetics of prostaglandin E₁ during continuous intravenous infusion in patients with adult respiratory distress syndrome. Am Rev Respir Dis 1988; 137: 5-12.
• 13 Dawson W, Boot JR, Cockerill AF, Mallen DNB, Osborne DJ. Release of novel prostaglandins and thromboxanes after immunological challenge of guinea-pig lung. Nature 1976; 262: 699-702.
• 14 Dusting GJ, Mencada S, Vane JR. Recirculation of prostacyclin (PGI₂) in the dog. Br J Pharmacol 1978; 64: 315-20.
• 15 Falke KJ, Rossaint P, Pison U, Slama K, Lopez F, Santak B, Zapol WM. Inhaled nitric oxide selectively reduces pulmonary hypertension in severe ARDS and improves gas exchange as well as right heart ejection fraction - a case report. Am Rev Respir Dis 1991; 143: A248.
• 16 Farber HW, Karlinsky JB, Faling LJ. Fatal outcome following nifidepine in primary pulmonary hypertension. Chest 1983; 83: 708-9.
• 17 Feddersen CO, Mathias M, Murphy RC, Reeves JT, Voelkel NF. Leukotriene E4 causes pulmonary vasoconstriction, not inhibited by meclofenamate. Prostaglandins 1983; 26: 869-83.
• 18 Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilatator reversing hypoxic pulmonary vasoconstricting. Circulation 1991; 83: 2038-47.
• 19 Garrett RC, Thomas HM. Relation of prostanoids to strength of hypoxic vasoconstriction in dogs with lobar atelectasis. I Appl Physiol 1985; 59: 72-7.
• 20 Groves BM, Ditchey RV, Reeves JT, Frosolono MF, Long WA. Comparison of prostacyclin to acute and chronic diltiazem in primary pulmonary hypertension. JACC 1985; 05: 442A.
• 21 Groves BM, Rubin LJ, Reeves JT, Frosolono MF. A comparison of the acute hemodynamic effects of prostacyclin and hydralazine in primary pulmonary hypertension. Am Heart J 1985; 110: 1200-4.
• 22 Guadagni DN, Ikram H, Maslowski AH. Haemodynamic effects of prostacyclin in pulmonary hypertension. Br Heart J 1981; 45: 385-8.
• 23 Hermiller JB, Bambach D, Thompson MJ. Vasodilators and prostaglandin inhibitors in primary pulmonary hypertension. Ann Intern Med 1982; 97: 480-9.
• 24 Higgenbottam T, Wells F, Wheeldon D, Wallwork J. Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin). Lancet 1984; 02: 1046-7.
• 25 Holcroft JW, Vassar MJ, Weber CJ. Prostaglandin E₁ and Survival in Patients with the Adult Respiratory Distress Syndrome. Ann Surg 1986; 203: 371-8.
• 26 Hsueh W, Arroyave CM, Jordan RL. Identification of C3b as the major serum protein that stimulates prostaglandin and thromboxane synthesis by macrophages. Prostaglandins 1984; 28: 889-903.
• 27 Jones DK, Higenbottam T, Wallwork J. Practical experience of long term prostacyclin in patients with primary pulmonary hypertension. Am Rev Respir Dis 1985; 131: 85A.
• 28 Jones DK, Higenbottam T, Wallwork J. Pulmonary vasodilatation with prostacyclin in primary pulmonary hypertension. Chest 1989; 96: 784-9.
• 29 Jones DK, Higenbottam T, Wallwork J. Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin). Br Heart J 1987; 57: 270-8.
• 30 Leffler CW, Green RS, Jerkins RK, Horton JL, Desiderio DM, Cassin S. Arachidonic acid metabolism by neonatal lungs perfused with Krebs bicarbonate buffer. Prostagl Leukotr Med 1984; 15: 115-28.
• 31 Leffler CW, Hessler JR, Terragno NA. Ventilation-induced release of prostaglandinlike material from fetal lungs. Am J Physiol 1980; 238: H282-6.
• 32 Littner M, Kazmi G, Lott F, Golub M, Berger M. Cyclooxygenase products and cyclic nucleotid levels with infusion of arachidonic acid, PGI₂, PGE₂, PGF₂, and 6-keto-PGF₁ in an isolated dog lung. Am Rev Respir Dis 1983; 128: 868-74.
• 33 Manier G, Castaing Y, Guenard H. Determinants of hypoxemia during the acute phase of pulmonary embolism in humans. Am Rev Respir Dis 1985; 132: 332-8.
• 34 Mélot C, Lejeune PH, Leeman M, Moraine JJ, Naeije R. Prostaglandin E₁ in the adult respiratory distress syndrome. Benefit for pulmonary hypertension and cost for pulmonary gas exchange. Am Rev Respir Dis 1988; 139: 106-10.
• 35 Naeije R, Mélot C, Mols P, Hallemans R. Reduction in pulmonary hypertension by prostaglandin E₁ in decompensated chronic obstructive pulmonary disease. Am Rev Respir Dis 1982; 125: 1-5.
• 36 Naeije R, Mélot C, Mols P, Hallemans R. Reduction in pulmonary hypertension by prostaglandin E₁ in decompensated chronic obstructive pulmonary disease. Acta Ther 1980; 06: 29.
• 37 Neuhof H, Noack A, Hoffmann C, Seeger W. Thromboxane-mediated pulmonary vasoconstriction in rabbits induced by acute alveolar hypoxia. In: Prostaglandins and other Eicosanoids in the cardiovascular system. Schrör (Hrsg). Basel: Karger: 1985: 328-34.
• 38 Palavesky HI, Long W, Crow J, Fishman AP. Prostacyclin and acetylcholine as screening agents for acute pulmonary vasodilator responsiveness in primary pulmonary hypertension. Circulation 1990; 82: 2018-26.
• 39 Palavesky HI, Schloo BL, Pietra GG, Weber KT, Janicki JS, Rubin E, Fishman AP. Primary pulmonary hypertension: Vascular structure, morphometry, and responsiveness to vasodilatator agents. Circulation 1989; 76: 135-41.
• 40 Payen D, Gatecel C, Guinard N. Inhalation of low dose of NO and IV L-Arg in ARDS: effect on pulmonary hemodynamic and gaz exchange. Int Care Med 1992; 18: Alll.
• 41 Pittet JF, Lacroix JS, Gunning K, Laverriere MC, Morel DR, Suter PM. Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. Chest 1990; 98: 1467-72.
• 42 Radermacher P, Santak B, Becker H, Falke KJ. Prostaglandin E₁ and nitroglycerin reduce pulmonary capillary pressure but worsen ventilation-perfusion distributions in patients with adult respiratory distress syndrome. Anesthesiology 1989; 70: 601-6.
• 43 Radermacher P, Santak B, Wüst HJ, Tarnow J, Falke KJ. Prostacyclin and right ventricular functions in patients with pulmonary hypertension associated with ARDS. Int Care Med 1990; 16: 227-32.
• 44 Rich S, Levy PS. Characteristics of surviving and nonsurviving patients with primary pulmonary hypertension. Am J Med 1984; 76: 573.
• 45 Richardson A, Wells FC, Branthwaite MA. Use of prostacyclin and ultrafiltration in adult respiratory distress syndrome. Int Care Med 1984; 10: 107-9.
• 46 Robinson C, Hardy CC, Holgate ST. Pulmonary synthesis, release, and metabolism of prostaglandins. J Allergy Clin Immunol 1985; 76: 265-71.
• 47 Robinson C, Peers SH, Waddell KA, Blair IA, Hoult JRS. Thromboxane B₂ uptake and metabolism in isolated perfused lung. Identification and comparison with prostaglandin F_2á . Biochim Biophys Acta 1982; 712: 315-25.
• 48 Rossaint R, Falke KJ, Keitel M, Lopez F, Pison U, Slama K, Griming T, Lewandowski K, Zapol WM. Inhaled nitric oxide in severe ARDS. Int Care Med 1992; 18: A109.
• 49 Ruzkovec A, Stradling J, Minty K, Shepard G, Oakley CM. Hydralazine in pulmonary hypertension. N Engl J Med 1982; 307: 1214-5.
• 50 Rubin LJ, Groves BM, Reeves JT, Frosolono M, Handel F, Cato AE. Prostacyclininduced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation 1982; 66: 334-8.
• 51 Rubin LJ, Mendoza J, Hcod M, McGoon M, Barst R, Williams WB, Diehl JH, Crow J, Long W. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Intern Med 1990; 112: 485-91.
• 52 Russell JA, Ronco JJ, Dodek PM. Physiologic effects and side effects of prostaglandin E₁ in the adult respiratory distress syndrome. Chest 1990; 97: 684-92.
• 53 Said SI. Pulmonary metabolism of prostaglandins and vasoactive peptides. Ann Rev Physiol 1982; 44: 257-68.
• 54 Sakaguchi K, Tanaka N, Sawada N, Araki Y, Fujita K. Vasodilator therapy for right ventricular failure. Jpn Cire J 1984; 48: 357-64.
• 55 Scott WA, Rouzer CA, Cohn ZA. Leukotriene C release by macrophages. Fed Proc 1983; 42: 129-33.
• 56 Seeger W, Bauer M, Bhakdi S. Staphylococcal alpha-toxin elicits hypertension in isolated rabbit lungs. Evidence for thromboxane formation and the role of extracellular calcium. J Clin Invest 1984; 74: 849-58.
• 57 Seeger W, Birkemeyer RG, Ermert L, Suttorp N, Bhakdi S, Duncker HR. Staphylococcal á-toxin-induced vascular leakage in isolated perfused rabbit lungs. Lab Invest 1990; 63: 341-9.
• 58 Seeger W, Hartmann R, Neuhof H, Bhakdi S. Local complement activation, thromboxane-mediated vasoconstriction, and vascular leakage in isolated lungs. Am Rev Respir Dis 1989; 139: 88-99.
• 59 Seeger W, Grimminger F, Barden M, Bekker G, Lohmeyer J, Heinrich D, Lasch HG. Omega-oxidized leukotriene B₄ detected in the lavage fluid of patients with non-cardiogenic pulmonary edema, but not in those with cardiogenic edema. Int Care Med 1991; 17: 1-6.
• 60 Seeger W, Lasch HG. Septic Lung. Rev Infect Dis 1987; 21 1, 570-9.
• 61 Seeger W, Menger M, Walmrath D, Becker G, Grimminger F, Neuhof H. Arachidonic lipoxygenase pathways and increased vascular permeability in isolated rabbit lungs. Am Rev Respir Dis 1987; 136: 964-72.
• 62 Seeger W, Neuhof H. Pathophysiologie der Lungenembolie. Hämostaseologie 1984; 04: 72-82.
• 63 Seeger W, Obernitz R, Thomas M, Walmrath D, Holland IB, Grimminger F, Eberspächer B, Hugo F, Suttorp N, Bhakdi S. Lung vascular injury after administration of viable hemolysing-forming Escherichia coli in isolated rabbit lungs. Am Rev Respir Dis 1991; 143: 797-805.
• 64 Seeger W, Stöhr G, Wolf HRD, Neuhof H. Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer. J Appl Physiol 1985; 58: 326-38.
• 65 Seeger W, Suttorp N, Grimminger F, Bhakdi S. Bacterial exotoxins and vascular injury. In: Pathophysiology of shock, sepsis, and organ failure. Schlag G. (Hrsg). Berlin: Springer Verlag; 1993. im Druck.
• 66 Seeger W, Walmrath D, Menger M, Neuhof H. Increased lung vascular permeability after arachidonic acid and hydrostatic challenge. J Appl Physiol 1986; 61: 1781-9.
• 67 Seeger W, Walter H, Suttorp N, Muhly M, Bhakdi S. Thromboxane-mediated hypertension and vascular leakage evoked by low doses of Escherichia coli Hemolysin in rabbit lungs. J Clin Invest 1989; 84: 220-7.
• 68 Seeger W, Walter H, Suttorp N, Muhly M, Bhakdi S. Thromboxane-mediated hypertension and vascular leakage evoked by low doses of Escherichia coli hemolysin in rabbit lungs. J Clin Invest 1989; 84: 220-7.
• 69 Shoemaker WC, Appel PL. Effects of prostaglandin E₁ in adult respiratory distress syndrome. Surgery 1986; 99: 275-82.
• 70 Silverman HJ, Slotman G, Bone RC, Maunder R, Hyers TM, Kerstein MD, Ursprung JJ. Effects of prostaglandin E₁ on oxygen delivery and consumption in patients with the adult respiratory distress syndrome. Chest 1990; 98: 405-10.
• 71 Suttorp N, Seeger W, Dewein E, Bhakdi S, Roka L. Staphylococcal á-toxin stimulates synthesis of prostacyclin by cultured endothelial cells from pig pulmonary arteries. Am J Physiol 1985; 248: C127-35.
• 72 Todd MH, Cragg DBJ, Forrest JB. The involvement of prostaglandins and thromboxanes in the response to pulmonary embolism in anaesthetized rabbits and isolated perfused lungs. Thrombos Res 1983; 30: 81-90.
• 73 Tokioka H, Kobayashi O, Ohta Y, Wakabayashi T, Kosaka F. The acute effects of prostaglandin E₁ on the pulmonary circulation and oxygen delivery in patients with the adult respiratory distress syndrome. Int Care Med 1985; 11: 61-4.
• 74 Uotila P, Hiltunen A, Mäkilä K, Männistö J, Toivonen H, Hartiala J. The metabolism of arachidonic acid in isolated hamster, rat and guinea pig lungs. Prostagl Med 1980; 05: 149-62.
• 75 Utsunomiya T, Krausz MM, Levine L, Shepro D, Hechtmann HB. Thromboxane mediation of cardiopulmonary effects of embolism. J Clin Invest 1982; 70: 361-8.
• 76 Utsunomiya T, Krausz MM, Valeri CR, Shepro D, Hechtman B. Treatment of aspiration pneumonia with ibuprofen and prostacyclin. Surgery 1981; 90: 170-6.
• 77 Wagner PD. Ventilation-perfusion relationships. Clin Physiol 1981; 01: 437-51.
• 78 Walmrath D, Griebener M, Kolb B, Grimminger F, Bhakdi S, Galanos C, Schade U, Seeger W. Endotoxin primes rabbit lungs for enhanced pulmonary hypertension, but not vascular leakage, in response to Staphylococcal á-toxin. Eingereicht zur Publikation..
• 79 Walmrath D, König R, Ernst C, Brückner H, Grimminger F, Seeger W. Ventilationperfusion relationship in isolated blood-free perfused rabbit lungs. J Appl Physiol 1992; 72: 374-82.
• 80 Walmrath D, Pilch J, Scharmann MR, Grimminger F, Seeger W. Severe ventilation-perfusion mismatch in perfused rabbit lungs evoked by sequential intravascular challenge with endotoxin and E. coli hemolysin. Eingereicht zur Publikation..
• 81 Walmrath D, Scharmann M, König R, Pilch J, Grimminger F, Seeger W. Staphylococcal á-toxin induced ventilation-perfusion mismatch in isolated blood-free perfused rabbit lungs. J Appl Physiol. in Druck.
• 82 Watkins WD, Peterson MB, Crone RK, Shanon DC, Levine L. Prostacyclin and prostaglandin E₁ for severe idiopathic pulmonary artery hypertension. Lancet 1980; 02: 1083.
• 83 Weidener WJ. Effects of inomethacin on pulmonary hemodynamics and extravascular lung water in sheep after pulmonary microembolism. Prostaglandins Med 1979; 03: 71-80.