Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Inhalation of prostacyclin (PGI2) for 8 hours does not produce signs of acute pulmonary toxicity in healty lambs

  • 41 Accesses

  • 31 Citations

Abstract

Objective

To study the potential side effects and toxicity of inhaling prostacyclin (PGI2) aerosol for 8 h.

Design

In a prospective, randomized study 14 healthy lambs received either PGI2 (n=7) or 0.9% NaCl (n=7) as an aerosol for 8 h.

Setting

Institute for Surgical Research of the Ludwig-Maximilians-University of Munich.

Interventions

All animals were studied under general anesthesia in a prone position. They were first intubated endotracheally and later tracheotomized. PGI2 solution (median dose 28 ng/kg per min) or 0.9% NaCl was administered with a jet nebulizer (delivery rate 4–10 ml/h; mass median diameter of aerosol particles 3.1 μm). Bronchoalveolar lavage was performed before and after the inhalation period to collect epithelial lining fluid of alveoli.

Measurements and results

Hemodynamic and respiratory parameters, systemic resorption (plasma levels of 6-keto-prostaglandin-F1α), in vitro bleeding time, collagen-induced platelet aggregation and global biochemical and cellular composition of the epithelial lining fluid were examined in order to assess the sie effects and signs of acute pulmonary toxicity induced by inhaled PGI2. No statistically significant differences were found between the PGI2 and the control groups for any of the parameters examined.

Conclusion

Inhalation of PGI2 (28 ng/kg per min) over a period of 8 h in healthy lambs does not produce major side effects or acute pulmonary toxicity.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Radermacher P, Santak B (1991) Vasodilating agents in ARDS. In: Vincent JL (ed) Update in intensive care and emergency medicine. Springer, Berlin Heidelberg New York, pp 307–309

  2. 2.

    Sibbald WJ, Driedger AA, Myers ML, Short AI, Wells GA (1983) Biventricular function in the adult respiratory distress syndrome. Chest 84: 126–134

  3. 3.

    Prielipp RC, McLean R, Rosenthal MH, Pearl RG (1991) Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in experimental porcine pulmonary hypertension. Crit Care Med 19:60–67

  4. 4.

    Radermacher P, Santak B, Wust HJ, Tarnow J, Falke KJ (1990) Prostacyclin for the treatment of pulmonary hypertension in the adult respiratory distress syndrome: effects on pulmonary capillary pressure and ventilation-perfusion distributions. Anesthesiology 72: 238–244

  5. 5.

    Welte M, Zwissler B, Habazettl H, Messmer K (1993) PGI2 aerosol versus nitric oxide for selective pulmonary vasodilation in hypoxic pulmonary vasoconstriction. Eur Surg Res 25: 329–340

  6. 6.

    Walmrath D, Schneider T, Pilch J, Grimminger F, Seeger W (1993) Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet 342:961–962

  7. 7.

    Bein T, Pfeifer M, Riegger G, Taeger K (1994) Continuous intraarterial measurements of oxygenation during aerosolized prostacyclin administration in severe respiratory failure (correspondence). N Engl J Med 331:335–336

  8. 8.

    Marggraf G, Balzerreit A, Schönfelder B, Doetsch N, Zerkowski HR, Reidemeister JC (1994) Hamodynamische Effekte von Epoprostenol als Aerosol zur selektiven pulmonalen Vasodilatation versus intravenöse Applikation nach kardiochirurgischer Intervention. Anaesthesist 43 [Suppl 1]:S209

  9. 9.

    Walmrath D, Grimminger F, Schneider T, Pilch J, Seeger W (1994) Effects of aerosolized PGI2 on gas exchange and pulmonary hemodynamics in patients with acute respiratory failure. Intensive Care Med 20 [Suppl 2]:S 58

  10. 10.

    Bindl L, Fahnenstich H, Peukert U (1994) Aerosolised prostacyclin for pulmonary hypertension in neonates. Arch Dis Child Fetal Neonatal 71: F214-F216

  11. 11.

    Santak B, Schreiber M, Kuen P, Lang D, Radermacher P, (1995) Prostacyclin aerosol in an infant with pulmonary hypertension. Eur J Pediatr 154:233–235

  12. 12.

    Walmrath D, Schneider T, Pilch J, Schermuly R, Grimminger F, Seeger W (1995) Effects of aerosolized prostacyclin in severe pneumonia. Am J Respir Crit Care Med 151:724–730

  13. 13.

    Zwissler B, Rank N, Jaenicke U, Schürle B, Welte M, Reichart B, Netz H, Messmer K, Peter K (1995) Selective pulmonary vasodilation by inhaled prostacyclin in a newborn with congenital heart disease and cardiopulmonary bypass. Anesthesiology 82:1512–1516

  14. 14.

    Pappert D, Busch T, Gerlach H, Lewandowski K, Radermacher P, Rossaint R (1995) Aerosolized prostacyclin versus inhaled nitric oxide in children with severe acute respiratory distress syndrome. Anesthesiology 82:1507–1511

  15. 15.

    Burghuber OC, Silberbauer K, Haber P, Sinzinger H, Elliott M, Leithner C (1984) Pulmonary and antiaggregatory effects of prostacyclin after inhalation and intravenous infusion. Respiration 45:450–455

  16. 16.

    Szczeklick A, Gryglewski RJ, Nizankowska E, Nizankowska R, Musial J (1978) Pulmonary and anti-platelet effects of intravenous and inhaled prostacyclin in man. Prostaglandins 16: 651–660

  17. 17.

    Parsargiklian M, Bianco S (1980) Ventilatory and cardiovascular effects of prostacyclin and 6-oxo-PGF1 alpha by inhalation. Adv Prost Thromb Res 7: 943–951

  18. 18.

    Hardy CC, Bradding P, Robinson C, Holgate ST (1988) Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma. J Appl Physiol 64:1567–1574

  19. 19.

    Holt JP, Rhode EA, Kines H (1968) Ventricular volumes and body weight in mammals. Am J Physiol 215:704–715

  20. 20.

    Kelman GR (1966) Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol 21:1375–1376

  21. 21.

    Rennard SI, Basset G, Lecossier D, O'Donnell K, Pinkston P, Martin P, Crystal R (1986) Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol 60:532–538

  22. 22.

    Ludbrook J (1994) Repeated measurements and multiple comparisons in cardiovascular research. Cardiovasc Res 28:303–311

  23. 23.

    Bahkle YS, Ferreira SH (1985) Lung metabolism of eicosanoids: prostaglanddins, prostacylin, thromboxane, and leukotrienes. In: Fishman AP, Fisher AB (eds) Handbbok of physiology, sect. 3: the respiratory system, American Physiological Society, Bethesda, MD, pp 365–386

  24. 24.

    Roberts AM, Schultz HD, Green JF, Armstrong DJ, Kaufman MP, Coleridge HM, Coleridge JCG (1985) Reflex tracheal contraction evoked in dogs by bronchodilator prostaglandins E2 and I2. J Appl Physiol 58:1823–1831

  25. 25.

    Henderson RF, Rebar AH, Pickrell JA, Newton GJ (1979) Early damage indicators in the lung. III. Biochemical and cytological response of the lung to inhaled metal salts. Toxicol Appl Pharmacol 50:123–136

  26. 26.

    Beck BD, Brain JD, Bohannon DE (1982) An in vivo hamster bioassay to assess the toxicity of particulates for the lungs. Toxicol Appl Pharmacol 66: 9–29

  27. 27.

    Hubbard GB, Langlinais PC, Shimazu T, Okerberg CV, Mason AD, Pruitt BA (1991) The morphology of smoke inhalation injury in sheep. J Trauma 31: 1477–1486

  28. 28.

    Henderson RF (1988) Use of bronchoalveolar lavage to detect lung damage. In: Gardner DE, Crapo JD, Massaro EJ (eds) Toxicology of the lung. Raven Press, New York, pp 239–268

  29. 29.

    Taylor AE, Guyton AC, Bishop VS (1965) Permeability of the alveolar membrane to solutes. Circ Res 16: 353–362

  30. 30.

    Adams FH, Moss AJ, Fagan L (1963) The tracheal fluid in the fetal lamb. Biol Neonat 5:151–158

  31. 31.

    Brain JD, Beck BD (1985) Bronchoalveolar lavage. In: Witschi HP, Brain JD (eds) Toxicology of inhaled materials. Springer, Berlin Heidelberg New York, pp 203–226

  32. 32.

    Von Essen SG, Robbins RA, Spurzem JR, Thompson AB, mcGranaghan S, Rennard SI (1991) Bronchoscopy with bronchoalveolar lavage causes neutrophil recruitment in the lower respiratory tract. Am Rev Respir Dis 144:848–854

Download references

Author information

Correspondence to O. Habler.

Additional information

PGI2 (Flolan) was supplied by Wellcome, London, UK

The study was supported, in part, by the Deutsche Forschungsgemeinschaft, grant zw 37/4-1

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Habler, O., Kleen, M., Zwissler, B. et al. Inhalation of prostacyclin (PGI2) for 8 hours does not produce signs of acute pulmonary toxicity in healty lambs. Intensive Care Med 22, 426–433 (1996). https://doi.org/10.1007/BF01712159

Download citation

Key words

  • Aerosols
  • Epoprostenol
  • Toxicity
  • Lung