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Critical Care

, 17:R99

First Online: 27 May 2013Received: 22 November 2012Revised: 28 January 2013Accepted: 27 May 2013


IntroductionThe 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.

InterventionsOld 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.

ResultsCompared 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.

ConclusionsVentilation 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.

Keywordsventilator-induced lung injury age mechanical ventilation tidal volume volutrauma inflammation cytokines lung lavage AbbreviationsCOcardiac output

CVPcentral venous pressure

FiO2fraction of inspired oxygen

IL-1βInterleukin 1β

IL-6interleukin 6

MAPmean arterial pressure

MIP 2Macrophage inflammatory protein

MVmechanical ventilation

PaO2arterial oxygen tension

PEEPpositive end-expiratory pressure

TWBCtotal white blood cell count

VILIventilator induced lung injury

VTtidal volume

WD ratiowet-to-dry weight ratio

Electronic supplementary materialThe online version of this article doi:10.1186-cc12744 contains supplementary material, which is available to authorized users.

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Autor: Florian Setzer - Karsten Oschatz - Lars Hueter - Barbara Schmidt - Konrad Schwarzkopf - Torsten Schreiber


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