Effects of three controlled mechanical ventilation modes on rat lung hydrogen peroxide and apoptosis during hemorrhagic shock


Hemorrhagic shock causes a reduction in oxygen supply to tissues leading to increased reactive oxygen species resulting in lung injury. Often mechanical ventilation is required as supportive treatment; however, ventilation can also induce lung injury and apoptosis. The purpose of this study was to examine the effects of three modes of controlled mechanical ventilation: volume control, pressure control, and pressure regulated volume control on lung injury as measured by hydrogen peroxide and apoptosis during hemorrhagic shock. Male Sprague-Dawley rats were randomized to the three controlled mechanical ventilation groups. Hemorrhagic shock was elicited by removing approximately 40% of the blood volume over 30 minutes. The rats were treated with one of three modes of mechanical ventilation with 40% oxygen for 60 minutes. The lungs were removed and measured for hydrogen peroxide and apoptosis based on nuclear differential dye uptake. There were no significant differences in hemodynamics, arterial blood values, peak inspiratory pressures, tidal volume, respiratory rates, and intrathoracic pressures across three groups. However, lung hydrogen peroxide production and apoptosis were significantly increased in volume control and pressure control, compared to pressure-regulated volume control. In this study, early signs of ventilator induced lung injury were not detected using commonly employed clinical measurements. However, when examining lung cellular injury (hydrogen peroxide and apoptosis), we were able to measure significant lung damage in volume control and pressure control, but not pressure-regulated volume control. Thus, our results suggest that pressure-regulated volume control is the preferable mode of mechanical ventilation during hemorrhagic shock.

Share and Cite:

Thimmesch, A. , Shen, Q. , Clancy, R. and Pierce, J. (2013) Effects of three controlled mechanical ventilation modes on rat lung hydrogen peroxide and apoptosis during hemorrhagic shock. Open Journal of Molecular and Integrative Physiology, 3, 27-35. doi: 10.4236/ojmip.2013.31005.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Makley, A.T., Goodman, M.D., Friend, L.A., Deters, J.S., Johannigman, J.A., Dorlac, W.C., et al. (2010) Resuscitation with fresh whole blood ameliorates the inflammatory response after hemorrhagic shock. Journal of Trauma, 68, 305-311. doi:10.1097/TA.0b013e3181cb4472
[2] Bdeir, K., Higazi, A.A., Kulikovskaya, I., ChristofidouSolomidou, M., Vinogradov, S.A., Allen, T.C., et al. (2010) Neutrophil alpha-defensins cause lung injury by disrupting the capillary-epithelial barrier. American Journal of Respiratory and Critical Care Medicine, 181, 935946. doi:10.1164/rccm.200907-1128OC
[3] Tasoulis, M.K., Livaditi, O., Stamatakos, M., Stefanaki, C., Paneris, P., Prigouris, P., et al. (2009) High concentrations of reactive oxygen species in the BAL fluid are correlated with lung injury in rabbits after hemorrhagic shock and resuscitation. The Tohoku Journal of Experimental Medicine, 219, 193-199. doi:10.1620/tjem.219.193
[4] Lionetti, V., Recchia, F.A. and Ranieri, V.M. (2005) Overview of ventilator-induced lung injury mechanisms. Current Opinion in Critical Care, 11, 82-86. doi:10.1097/00075198-200502000-00013
[5] Yamamoto, H., Teramoto, H., Uetani, K., Igawa, K. and Shimizu, E. (2002) Cyclic stretch upregulates interleukin-8 and transforming growth factor-beta1 production through a protein kinase C-dependent pathway in alveolar epithelial cells. Respirology, 7, 103-109. doi:10.1046/j.1440-1843.2002.00377.x
[6] Bouadma, L., Dreyfuss, D., Ricard, J.D., Martet, G. and Saumon, G. (2007) Mechanical ventilation and hemorrhagic shock-resuscitation interact to increase inflammatory cytokine release in rats. Critical Care Medicine, 35, 2601-2606. doi:10.1097/01.CCM.0000286398.78243.CE
[7] Spieth, P.M., Guldner, A., Carvalho, A.R., Kasper, M., Pelosi, P., Uhlig, S., et al. (2011) Open lung approach vs acute respiratory distress syndrome network ventilation in experimental acute lung injury. British Journal of Anaesthesiology, 107, 388-397. doi:10.1093/bja/aer144
[8] Chapman, K.E., Sinclair, S.E., Zhuang, D., Hassid, A., Desai, L.P. and Waters, C.M. (2005) Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. American Journal of Physiology: Lung Cellular and Molecular Physiology, 289, L834-L841. doi:10.1152/ajplung.00069.2005
[9] Syrkina, O., Jafari, B., Hales, C.A. and Quinn, D.A. (2008) Oxidant stress mediates inflammation and apoposis in ventilator-induced lung injury. Respirology, 13, 333-340. doi:10.1111/j.1440-1843.2008.01279.x
[10] Le, A., Damico, R., Damarla, M., Boueiz, A., Pae, H.H., Skirball, J., et al. (2008) Alveolar cell apoptosis is dependent on p38 MAP kinase-mediated activation of xanthine oxidoreductase in ventilator-induced lung injury. Journal of Applied Physiology, 105, 1282-1290. doi:10.1152/japplphysiol.90689.2008
[11] Mach, W.J., Thimmesch, A.R., Slusser, J.G., Clancy, R.L. and Pierce, J.D. (2010) The effects of increased inspired oxygen with and without dopamine on lung and diaphragm hydrogen peroxide and apoptosis following hemorrhagic shock. Journal of Pre-Clinical and Clinical Research, 4, 5-10.
[12] Goodyear-Bruch, C., Simon, K., Hall, S., Mayo, M.S. and Pierce, J.D. (2005) Comparison of a visual to a computerassisted technique for detecting apoptosis. Biological Research for Nursing, 6, 180-186. doi:10.1177/1099800404271869
[13] Marcy, T.W. (1993) Barotrauma: Detection, recognition, and management. Chest, 104, 578-584. doi:10.1378/chest.104.2.578
[14] Gattinoni, L., Protti, A., Caironi, P. and Carlesso, E. (2010) Ventilator-induced lung injury: The anatomical and physiological framework. Critical Care Medicine, 38, S539-S548. doi:10.1097/CCM.0b013e3181f1fcf7
[15] Kallet, R.H., Campbell, A.R., Alonso, J.A., Morabito, D.J. and Mackersie, R.C. (2000) The effects of pressure control versus volume control assisted ventilation on patient work of breathing in acute lung injury and acute respiratory distress syndrome. Respiratory Care, 45, 1085-1096.
[16] Burns, S.M. (2008) Pressure modes of mechanical ventilation: The good, the bad, and the ugly. AACN Advanced Critical Care, 19, 399-411. doi:10.1097/01.AACN. 0000340721.78495.25
[17] Pierce, L. (2007). Management of the mechanically ventilated patient. 2nd Edition, Saunders, Maine.
[18] Crimi, E., Zhang, H., Han, R.N., Del Sorbo, L., Ranieri, V.M. and Slutsky, A.S. (2006) Ischemia and reperfusion increases susceptibility to ventilator-induced lung injury in rats. American Journal of Respiratory and Critical Care Medicine, 174, 178-186. doi:10.1164/rccm.200507-1178OC
[19] Cheifetz, I.M. (2003) Invasive and noninvasive pediatric mechanical ventilation. Respiratory Care, 48, 442-453.
[20] Dembinski, R., Henzler, D., Bensberg, R., Prusse, B., Rossaint, R. and Kuhlen, R. (2004) Ventilation-perfusion distribution related to different inspiratory flow patterns in experimental lung injury. Anesthesia and Analgesia, 98, 211-219. doi:10.1213/01.ANE.0000090319.21491.91
[21] Unzueta, M.C., Casas, J.I. and Moral, M.V. (2007) Pressure-controlled versus volume-controlled ventilation during one-lung ventilation for thoracic surgery. Anesthesia and Analgesia, 104, 1029-1033. doi:10.1213/01. ane.0000260313.63893.2f
[22] Li, L.F., Liao, S.K., Ko, Y.S., Lee, C.H. and Quinn, D.A. (2007) Hyperoxia increases ventilator-induced lung injury via mitogen-activated protein kinases: A prospective, controlled animal experiment. Critical Care, 11, R25. doi:10.1186/cc5704
[23] Tang, H., Lee, M., Budak, M.T., Pietras, N., Hittinger, S., Vu, M., et al. (2011) Intrinsic apoptosis in mechanically ventilated human diaphragm: Linkage to a novel Fos/ FoxO1/Stat3-Bim axis. The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 25, 2921-2936. doi:10.1096/fj.11-183798

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.