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Open Access 01-06-2013 | Research

Susceptibility to ventilator induced lung injury is increased in senescent rats

Authors: Florian Setzer, Karsten Oschatz, Lars Hueter, Barbara Schmidt, Konrad Schwarzkopf, Torsten Schreiber

Published in: Critical Care | Issue 3/2013

Abstract

Introduction

The principal mechanisms of ventilator induced lung injury (VILI) have been investigated in numerous animal studies. However, prospective data on the effect of old age on VILI are limited. Under the hypothesis that susceptibility to VILI is increased in old age, we investigated the pulmonary and extrapulmonary effects of mechanical ventilation with high tidal volume (VT) in old compared to young adult animals.

Interventions

Old (19.1 ± 3.0 months) and young adult (4.4 ± 1.3 months) male Wistar rats were anesthetized and mechanically ventilated (positive end-expiratory pressure 5 cmH2O, fraction of inspired oxygen 0.4, respiratory rate 40/minute) with a tidal volume (VT) of either 8, 16 or 24 ml/kg for four hours.

Respiratory and hemodynamic variables, including cardiac output, and markers of systemic inflammation were recorded throughout the ventilation period. Lung histology and wet-to-dry weight ratio, injury markers in lung lavage and respiratory system pressure-volume curves were assessed post mortem. Basic pulmonary characteristics were assessed in non-ventilated animals.

Results

Compared to young adult animals, high VT (24 ml/kg body weight) caused more lung injury in old animals as indicated by decreased oxygenation (arterial oxygen tension (PaO2): 208 ± 3 vs. 131 ± 20 mmHg; P <0.05), increased lung wet-to-dry-weight ratio (5.61 ± 0.29 vs. 7.52 ± 0.27; P <0.05), lung lavage protein (206 ± 52 mg/l vs. 1,432 ± 101; P <0.05) and cytokine (IL-6: 856 ± 448 vs. 3,283 ± 943 pg/ml; P <0.05) concentration. In addition, old animals ventilated with high VT had more systemic inflammation than young animals (IL-1β: 149 ± 44 vs. 272 ± 36 pg/ml; P <0.05 - young vs. old, respectively).

Conclusions

Ventilation with unphysiologically large tidal volumes is associated with more lung injury in old compared to young rats. Aggravated pulmonary and systemic inflammation is a key finding in old animals developing VILI.

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Slutsky AS: Lung injury caused by mechanical ventilation. Chest 1999, 116: 9S-15S. 10.1378/chest.116.suppl_1.9SCrossRefPubMed

Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P: Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med 2009, 151: 566-576. 10.7326/0003-4819-151-8-200910200-00011CrossRefPubMed

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VGM, Espósito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ: Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 2012, 308: 1651-1659. 10.1001/jama.2012.13730CrossRefPubMed

Imanaka H, Shimaoka M, Matsuura N, Nishimura M, Ohta N, Kiyono H: Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs. Anesth Analg 2001, 92: 428-436. 10.1213/00000539-200102000-00029CrossRefPubMed

Morita Y, Oda S, Sadahiro T, Nakamura M, Oshima T, Otani S, Hirasawa H: The effects of body temperature control on cytokine production in a rat model of ventilator-induced lung injury. Cytokine 2009, 47: 48-55. 10.1016/j.cyto.2009.04.004CrossRefPubMed

Copland IB, Martinez F, Kavanagh BP, Engelberts D, McKerlie C, Belik J, Post M: High tidal volume ventilation causes different inflammatory responses in newborn versus adult lung. Am J Respir Crit Care Med 2004, 169: 739-748. 10.1164/rccm.200310-1417OCCrossRefPubMed

Gomes RF, Shardonofsky F, Eidelman DH, Bates JH: Respiratory mechanics and lung development in the rat from early age to adulthood. J Appl Physiol 2001, 90: 1631-1638.PubMed

Kornecki A, Tsuchida S, Ondiveeran HK, Engelberts D, Frndova H, Tanswell AK, Post M, McKerlie C, Belik J, Fox-Robichaud A, Kavanagh BP: Lung development and susceptibility to ventilator-induced lung injury. Am J Respir Crit Care Med 2005, 171: 743-752. 10.1164/rccm.200408-1053OCCrossRefPubMed

Baati T, Bourasset F, Gharbi N, Njim L, Abderrabba M, Kerkeni A, Szwarc H, Moussa F: The prolongation of the lifespan of rats by repeated oral administration of [60]fullerene. Biomaterials 2012, 33: 4936-4946. 10.1016/j.biomaterials.2012.03.036CrossRefPubMed

10.

Altun M, Bergman E, Edström E, Johnson H, Ulfhake B: Behavioral impairments of the aging rat. Physiol Behav 2007, 92: 911-923. 10.1016/j.physbeh.2007.06.017CrossRefPubMed

11.

Wunsch H, Linde-Zwirble WT, Angus DC, Hartman ME, Milbrandt EB, Kahn JM: The epidemiology of mechanical ventilation use in the United States. Crit Care Med 2010, 38: 1947-1953.PubMed

12.

Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM: Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011, 364: 1293-1304. 10.1056/NEJMoa1011802CrossRefPubMed

13.

Ely EW, Wheeler AP, Thompson BT, Ancukiewicz M, Steinberg KP, Bernard GR: Recovery rate and prognosis in older persons who develop acute lung injury and the acute respiratory distress syndrome. Ann Intern Med 2002, 136: 25-36.PubMed

14.

Desai A, Grolleau-Julius A, Yung R: Leukocyte function in the aging immune system. J Leukoc Biol 2010, 87: 1001-1009. 10.1189/jlb.0809542PubMedCentralCrossRefPubMed

15.

Vallejo AN: Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease. Trends Mol Med 2007, 13: 94-102. 10.1016/j.molmed.2007.01.005CrossRefPubMed

16.

Esteban A, Anzueto A, Frutos-Vivar F, Alía I, Ely EW, Brochard L, Stewart TE, Apezteguía C, Tobin MJ, Nightingale P, Matamis D, Pimentel J, Abroug F: Outcome of older patients receiving mechanical ventilation. Intensive Care Med 2004, 30: 639-646. 10.1007/s00134-004-2160-5CrossRefPubMed

17.

Villar J, Pérez-Méndez L, Basaldúa S, Blanco J, Aguilar G, Toral D, Zavala E, Romera MA, González-Díaz G, Nogal FD, Santos-Bouza A, Ramos L, Macías S, Kacmarek RM: A risk tertiles model for predicting mortality in patients with acute respiratory distress syndrome: age, plateau pressure, and P(aO(2))/F(IO(2)) at ARDS onset can predict mortality. Respir Care 2011, 56: 420-428. 10.4187/respcare.00811CrossRefPubMed

18.

Chan A, Jayasuriya K, Berry L, Roth-Kleiner M, Post M, Belik J: Volutrauma activates the clotting cascade in the newborn but not adult rat. Am J Physiol Lung Cell Mol Physiol 2006, 290: L754-L760. 10.1152/ajplung.00339.2005CrossRefPubMed

19.

Calabresi C, Arosio B, Galimberti L, Scanziani E, Bergottini R, Annoni G, Vergani C: Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung. Exp Gerontol 2007, 42: 1003-1011. 10.1016/j.exger.2007.06.016CrossRefPubMed

20.

Sharma G, Goodwin J: Effect of aging on respiratory system physiology and immunology. Clin Interv Aging 2006, 1: 253-260. 10.2147/ciia.2006.1.3.253PubMedCentralCrossRefPubMed

21.

Nin N, Lorente JA, de Paula M, Fernández-Segoviano P, Peñuelas O, Sánchez-Ferrer A, Martínez-Caro L, Esteban A: Aging increases the susceptibility to injurious mechanical ventilation. Intensive Care Med 2008, 34: 923-931. 10.1007/s00134-007-0960-0CrossRefPubMed

22.

Lin C, Zhang H, Cheng K, Slutsky AS: Mechanical ventilation may increase susceptibility to the development of bacteremia. Crit Care Med 2003, 31: 1429-1434. 10.1097/01.CCM.0000063449.58029.81CrossRefPubMed

23.

Allen GB, Pavone LA, DiRocco JD, Bates JHT, Nieman GF: Pulmonary impedance and alveolar instability during injurious ventilation in rats. J Appl Physiol 2005, 99: 723-730. 10.1152/japplphysiol.01339.2004CrossRefPubMed

24.

Whitehead TC, Zhang H, Mullen B, Slutsky AS: Effect of mechanical ventilation on cytokine response to intratracheal lipopolysaccharide. Anesthesiology 2004, 101: 52-58. 10.1097/00000542-200407000-00010CrossRefPubMed

25.

Schreiber T, Hueter L, Gaser E, Schmidt B, Schwarzkopf K, Rek H, Karzai W: PEEP has beneficial effects on inflammation in the injured and no deleterious effects on the noninjured lung after unilateral lung acid instillation. Intensive Care Med 2006, 32: 740-749. 10.1007/s00134-006-0117-6CrossRefPubMed

26.

Schreiber T, Hueter L, Gaser E, Schmidt B, Schwarzkopf K, Karzai W: Effects of a catecholamine-induced increase in cardiac output on lung injury after experimental unilateral pulmonary acid instillation. Crit Care Med 2007, 35: 1741-1748. 10.1097/01.CCM.0000269374.85160.BFCrossRefPubMed

27.

Schreiber T, Hueter L, Schwarzkopf K, Hohlstein S, Schmidt B, Karzai W: Increased susceptibility to ventilator-associated lung injury persists after clinical recovery from experimental endotoxemia. Anesthesiology 2006, 104: 133-141. 10.1097/00000542-200601000-00019CrossRefPubMed

28.

Dreyfuss D, Saumon G: Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 1998, 157: 294-323. 10.1164/ajrccm.157.1.9604014CrossRefPubMed

29.

Choi W, Quinn DA, Park KM, Moufarrej RK, Jafari B, Syrkina O, Bonventre JV, Hales CA: Systemic microvascular leak in an in vivo rat model of ventilator-induced lung injury. Am J Respir Crit Care Med 2003, 167: 1627-1632. 10.1164/rccm.200210-1216OCCrossRefPubMed

30.

Hoegl S, Boost KA, Flondor M, Scheiermann P, Muhl H, Pfeilschifter J, Zwissler B, Hofstetter C: Short-term exposure to high-pressure ventilation leads to pulmonary biotrauma and systemic inflammation in the rat. Int J Mol Med 2008, 21: 513-519.PubMed

31.

Dreyfuss D, Ricard J, Saumon G: On the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury. Am J Respir Crit Care Med 2003, 167: 1467-1471. 10.1164/rccm.200206-611CPCrossRefPubMed

32.

Wilson MR, Choudhury S, Goddard ME, O'Dea KP, Nicholson AG, Takata M: High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury. J Appl Physiol 2003, 95: 1385-1393.CrossRefPubMed

33.

Zhang H, Downey GP, Suter PM, Slutsky AS, Ranieri VM: Conventional mechanical ventilation is associated with bronchoalveolar lavage-induced activation of polymorphonuclear leukocytes: a possible mechanism to explain the systemic consequences of ventilator-induced lung injury in patients with ARDS. Anesthesiology 2002, 97: 1426-1433. 10.1097/00000542-200212000-00014CrossRefPubMed

34.

Broccard AF, Vannay C, Feihl F, Schaller M: Impact of low pulmonary vascular pressure on ventilator-induced lung injury. Crit Care Med 2002, 30: 2183-2190. 10.1097/00003246-200210000-00002CrossRefPubMed

35.

Gardiner SM, Kemp PA, March JE, Woolley J, Bennett T: The influence of antibodies to TNF-alpha and IL-1beta on haemodynamic responses to the cytokines, and to lipopolysaccharide, in conscious rats. Br J Pharmacol 1998, 125: 1543-1550. 10.1038/sj.bjp.0702250PubMedCentralCrossRefPubMed

36.

Duncan DJ, Hopkins PM, Harrison SM: Negative inotropic effects of tumour necrosis factor-alpha and interleukin-1beta are ameliorated by alfentanil in rat ventricular myocytes. Br J Pharmacol 2007, 150: 720-726. 10.1038/sj.bjp.0707147PubMedCentralCrossRefPubMed

37.

Sahebjami H: Lung tissue elasticity during the lifespan of Fischer 344 rats. Exp Lung Res 1991, 17: 887-902. 10.3109/01902149109064324CrossRefPubMed

Title: Susceptibility to ventilator induced lung injury is increased in senescent rats
Authors: Florian Setzer
Karsten Oschatz
Lars Hueter
Barbara Schmidt
Konrad Schwarzkopf
Torsten Schreiber
Publication date: 01-06-2013
Publisher: BioMed Central
Published in: Critical Care / Issue 3/2013
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc12744

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Susceptibility to ventilator induced lung injury is increased in senescent rats

Abstract

Introduction

Interventions

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Interventions

Results

Conclusions

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