Eight hours' inhalation of prostacyclin (PGl2) in healthy lambs: Effects on tracheal, bronchial, and alveolar morphology
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To study potential toxic effects of long-term (8 h) inhaled prostacyclin (PGI2) on respiratory tract tissues.
In a prospective, randomized order, either PGI2 (n=7) or normal saline (n=7) was aerosolized during a time period of 8 h in healthy lambs.
Institute for Surgical Research of the Ludwig-Maximilians University of Munich.
14 healthy, anesthetized, ventilated lambs.
All animals were endotracheally intubated followed by tracheotomy. PGI2 solution or normal saline was administered with a jet nebulizer (delivery rate 4–10 ml/h; mass median diameter of aerosol particles 3.1 μm).
Measurements and results
Histomorphological changes after 8-h inhalation of PGI2 solution were compared to those after 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissues were examined by light and electron microscopy in order to assess tissue damage induced by inhaled PGI2. Pathological changes were ranked by a blinded observer following a graduation system ranging from “absence of pathological changes” to “maximal pathological changes”. Abnormalities were restricted to the trachea (focal flattening of the epithelium, loss of cilia, slight inflammatory cell infiltration) and alveolar tissue (focal alveolar septal thickening with slight inflammatory cell infiltration), but no statistically significant differences between the PGI2 and control groups were encountered.
Our findings indicate the absence of PGI2 aerosol-related respiratory tissue damage after 8-h inhalation of PGI2.
- Radermacher P, Santak B (1991) Vasodilating agents in ARDS. In: Vincent JL (ed) Update in intensve care and emergency medicine, 14th edn. Springer, Berlin Heidelberg New York, pp 307–309
- Sibbald WJ, Driedger AA, Myers ML, Short AI, Wells GA (1983) Biventricular function in the adult respiratory distress syndrome. Chest 84:126–134
- 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
- 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
- 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
- Booke M, Bradford W, Prien T, Hinder F, Harp D, Traber L (1995) Inhaliertes Stickstoffmonoxid versus Prostazyklin-Aerosol: eine Effektivitäts-und Dosisvergleichsstudie (abstract). Anaesthesist 44 [Suppl 1]:S76
- Walmarath D, Schneider T, Pilch J, Grimminger F, Seeger W (1993) Aerosolised prostacyclin in adult respiratory distress syndrom. Lancet 342:961–962
- Bein T, Pfeiffer M, Riegger G, Taeger K (1994) Continuous intraarterial measurements of oxygenation during aerosolized prostacyclin administration in severe respiratory failure. N Engl J Med 331:335–336
- 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 (abstract). Anaesthesist 43 [Suppl 1]:S209
- 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 (abstract). Intensive Care Med 20 [Suppl 2]:S58
- Bindl L, Fahnenstich H, Peukert U (1994) Aerosolised prostacyclin for pulmonary hypertension in neonates. Arch Dis Child Fetal Neonatal 71: F214-F216
- 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
- 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
- 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
- Habler O, Kleen M, Zwissler B, Pusch R, Welte M, Vogelmeier C, Kempter B, Krombach F, Messmer K (1996) Inhalation of prostacyclin (PGI2) for 8 hours does not produce signs of acute pulmonary toxicity in healthy lambs. Intensive Care Med 22:426–433
- Hayatoavoudi G, Craqo JD, Miller FJ, O'Neil FJ (1980) Factors determining degree of inflation in intratracheally fixed rat lungs. J Appl Physiol 48:389–393
- Pinkerton KE, Crapo JD (1985) Morphometry of the alveolar region of the lung. In: Witschi HP, Brain JD (eds) Toxicology of inhaled materials. Springer, Berlin Heidelberg, pp 259–285
- Bastacky J, Hayes TL, von Revealed B (1983) Lung structures as revealed by microdissection: positional morphology of human lung. Am J Respir Crit Care Med 128:S7-S13
- 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
- Fuller HD, Dolovich MB, Posmituck G, Wong Pack W, Newhouse MT (1990) Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients: comparison of dose to the lungs. Am J Respir Crit Care Med 141:440–444
- Webb HH, Tierney DF (1974) Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Am J Respir Crit Care Dis 110:556–565
- John E, McDevitt M, Wilborn W, Cassady G (1982) Ultrastructure of lung after ventilation. Br J Exp Pathol 63:401–407
- Eight hours' inhalation of prostacyclin (PGl2) in healthy lambs: Effects on tracheal, bronchial, and alveolar morphology
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- 1. Institute for Surgical Research, Ludwig-Maximilians University, Marchioninistraße 15, D-81366, Munich, Germany
- 2. Institute of Anesthesiology, Ludwig-Maximilians University, Munich, Germany
- 3. Projekt Inhalation, Center for Environmental and Medical Research, Neuherberg, Germany