Abstract
The effect of new ventilation strategies on initial pulmonary inflammatory reaction was studied in a surfactant-depleted piglet model. Sixty minutes after induction of lung injury by bronchoalveolar lavage, piglets received either aerosolized FC77 (aerosol-PFC, 10 mL/kg/h, n = 5) or partial liquid ventilation (PLV) with FC77 at functional residual capacity volume (FRC-PLV, 30 mL/kg, n = 5), or at low volume (LV-PLV, 10 mL/kg per hour, n = 5), or intermittent mandatory ventilation (control, n = 5). After 2 h, perfluorocarbon application was stopped and intermittent mandatory ventilation continued for 6 h. After a total experimental period of 8 h, animals were killed and lung tissue obtained. mRNA expression of IL-1β, IL-6, IL-8, and TGF-β in porcine lung tissue was quantified using TaqMan real-time PCR and normalized to β-actin (A) and hypoxanthine-guanine-phosphoribosyl-transferase (H). In the aerosol-PFC group, IL-1β, IL-6, IL-8, and transforming growth factor (TGF)-β mRNA expression in lung tissue was significantly lower than in the control group. Reduction was 95% for IL-1β/H (p < 0.001), 73% for IL-6/H (p < 0.05), 87% for IL-8/H (p < 0.001), and 38% for TGF-β/H (p < 0.01). A lower mRNA gene expression was also determined for IL-1β and IL-8 when the aerosol-PFC group was compared with the LV-PLV group [91% for IL-1β/H (p < 0.001), 75% for IL-8/H (p < 0.001)]. In the FRC-PLV group, mRNA expression of IL-1β was significantly lower than in the control (p < 0.05) and LV-PLV (p < 0.01) group. In a surfactant-depleted piglet model, aerosol therapy with perfluorocarbon but not LV-PLV reduces the initial pulmonary inflammatory reaction at least as potently as PLV at FRC volume.
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Abbreviations
- A:
-
β-actin
- BPD:
-
bronchopulmonary dysplasia
- Fio2:
-
inspiratory fraction of oxygen
- FRC:
-
functional residual capacity
- H:
-
hypoxanthine-guanine-phosphoribosyl-transferase
- IMV:
-
intermittent mandatory ventilation
- LV:
-
low volume
- PFC:
-
perfluorocarbon
- PLV:
-
partial liquid ventilation
- RU:
-
relative units
References
Speer CP 1999 Inflammatory mechanisms in neonatal chronic lung disease. Eur J Pediatr 158( suppl 1): 18–22
Özdemir A, Brown MA, Morgan WJ 1997 Markers and mediators of inflammation in neonatal lung disease. Pediatr Pulmonol 23: 292–306
Ogawa Y, Miyasaka, Kawano T, Imura S, Inukai K, Okuyama K, Oguchi K, Togari H, Nishida H, Mishina J 1993 A multicenter randomized trial of high frequency oscillatory ventilation as compared with conventional mechanical ventilation in preterm infants with respiratory failure. Early Hum Dev 32: 1–10
Clark RH, Gerstmann DR, Null DM, deLemos RA 1992 Prospective randomized comparison of high frequency oscillatory and conventional ventilation in respiratory distress syndrome. Pediatrics 89: 5–12
Gerstmann DR, Minton SD, Stoddard RA, Meredith KS, Monaco F, Bertrand JM, Battisti O, Langhendries JP, Francois A, Clark RH 1996 The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Pediatrics 98: 1044–1057
Demirakça S, Dötsch J, Knothe C, Magsaam J, Reiter HL, Bauer J, Kuehl PG 1996 Inhaled nitric oxide in neonatal and pediatric acute respiratory distress syndrome. Dose response, prolonged inhalation and weaning. Crit Care Med 24: 1913–1919
Houmes RJM, Verbrugge SJC, Hendrik ER, Lachmann B 1995 Hemodynamic effects of partial liquid ventilation with perfluorocarbon in acute lung injury. Intensive Care Med 21: 966–972
Lowe Leach C, Fuhrmann B, Morin FC, Rath MG 1993 Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome: a prospective, randomized, controlled study. Crit Care Med 21: 1270–1278
Overbeck MC, Pranikoff T, Yadao CM, Hirschl RB 1996 Efficacy of perfluorocarbon partial liquid ventilation in a large animal model of acute respiratory failure. Crit Care Med 24: 1208–1214
Quintel M, Heine M, Hirschl RB, Tillmanns R, Wessendorf V 1998 Effects of partial liquid ventilation on lung injury in a model of acute respiratory failure: A histologic and morphometric analysis. Crit Care Med 26: 833–843
Shaffer TH, Wolfson MR, Clark LC Jr 1992 Liquid ventilation. Pediatr Pulmonol 14: 102–109
Rotta AT, Gunnarsson B, Hernan LJ, Fuhrman BP, Steinhorn DM 1999 Partial liquid ventilation influences pulmonary histopathology in an animal model of acute lung injury. J Crit Care 14: 84–92
Croce MA, Fabian TC, Patton JH Jr, Melton SM, Moore M, Trenthem LL 1998 Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients. J Trauma 45: 273–282
Leach CL, Greenspan JS, Rubenstein SD, Shaffer TH, Wolfson MR, Jackson JC, DeLemos R, Fuhrman BP 1996 Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The LiquiVent Study Group. N Engl J Med 335: 761–767
Alliance Pharmaceutical Corp 2001 Preliminary results of LiquiVent® Phase 2–3 Clinical Study. Presented at the Annual Meeting of the American Thoracic Society, San Francisco, May 2001
Rotta AT, Steinhorn DM 1998 Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury. Crit Care Med 26: 1707–1715
Colton DM, Till GO, Johnson KJ, Dean SB, Barlett RH, Hirschl RB 1998 Neutrophil accumulation is reduced during partial liquid ventilation. Crit Care Med 26: 1716–1724
Smith TM, Steinhorn DM, Thusu K, Fuhrmann BP, Dandona P 1995 A liquid perfluorochemical decreases the in vitro production of reactive oxygen species by alveolar macrophages. Crit Care Med 23: 1533–1539
Lachmann B, Robertson B, Vogel J 1980 In vivo lung lavage as an experimental model of the respiratory distress syndrome. Acta Anaesth Scand 24: 231–236
MacIntyre N, Andjuval S, Baran G 1996 Aerosol deposition from an intra-airway aerosol. Eur Respir J 9( suppl 23): P0396
Dötsch J, Nüsken KD, Knerr I, Kirschbaum M, Repp R, Rascher W 1999 Leptin and neuropeptide Y gene-expression in human placenta: ontogeny and evidence for similarities to hypothalamic regulation. J Clin Endocrinol Metab 84: 2755–2758
Heid CA, Stevens J, Livak KJ, Williams PM 1996 Real time quantitative PCR. Genome Res 6: 986–994
Merz U, Kellinghaus M, Klosterhalfen B, Peschgens TH, Kurth A, Hörnchen H 2000 Inflammatory mediators in bronchioalveolar lavage after partial liquid ventilation (PLV) in surfactant-depleted newborn pigs. Eur J Med Res 5: 78
Wolfson MR, Kechner NE, Roache RF, DeChadarevian JP, Friss HE, Rubenstein SD, Shaffer TH 1998 Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency. J Appl Physiol 84: 624–40
Cannon ML, Cheifetz IM, Craig DM, Hubble CL, Quick G, Ungerleider RM, Smith PK, Meliones JN 1999 Optimizing liquid ventilation as a lung protection strategy for neonatal cardiopulmonary bypass: full functional residual capacity dosing is more effective than half functional residual capacity dosing. Crit Care Med 27: 1140–1146
Lim CM, Koh Y, Jung BO, Lee SD, Kim WS, Kim DS, Kim WD 2000 An optimal dose for respiratory mechanics in partial liquid ventilation for dependent lung-dominant acute lung injury. Chest 117: 199–204
Quintel M, Hirschl RB, Roth H, Loose R, van Ackern K 1998 Computer tomographic assessment of perfluorocarbon and gas distribution during partial liquid ventilation for acute respiratory failure. Am J Resp Crit Care Med 158: 249–255
Kandler MA, von der Hardt K, Schoof E, Dötsch J, Rascher W 2001 Persistent improvement of gas exchange and lung mechanics by aerosolized perfluorocarbon. Am J Resp Crit Care Med 164: 31–35
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The authors thank Sophie Brüggemeier and Julia Walther for excellent technical assistance.
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The study was supported by a grant of the IZKF (Interdisziplinäres Zentrum für Klinische Forschung), University of Erlangen-Nürnberg, Germany.
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Von Der Hardt, K., Schoof, E., Kandler, M. et al. Aerosolized Perfluorocarbon Suppresses Early Pulmonary Inflammatory Response in a Surfactant-Depleted Piglet Model. Pediatr Res 51, 177–182 (2002). https://doi.org/10.1203/00006450-200202000-00009
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DOI: https://doi.org/10.1203/00006450-200202000-00009
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