In healthy humans, ventilation is propelled by the rhythmic contraction of the diaphragm, the main muscle of inspiration. In contrast, in patients admitted to the intensive care unit, ventilation is carried out by a machine - to facilitate oxygen uptake in the lungs - and the diaphragm is inactive. However, mechanical ventilation is clearly a two-edged sword: recent studies suggest that during mechanical ventilation the diaphragm rapidly weakens. Thus, prolonged mechanical ventilation may be required because of diaphragm weakness caused by the mechanical ventilation itself. This so-called weaning failure is frequently encountered in ICU patients and contributes to mortality. My laboratory aims to unravel the complex pathophysiology of diaphragm weakness in critically ill patients. We particularly focus on the putative role of titin, a giant mechanosensor protein. For our studies we make use of genetically engineered mouse models and unique diaphragm biopsies of critically ill patients.
Coen Ottenheijm, PhD
Associate Professor, Cellular and Molecular Medicine - (Research Scholar Track)
Molecular Medicine Grad Program:
Yes
Bibliography
2020
Lindqvist, J., W. Ma, F. Li, Y. Hernandez, J. Kolb, B. Kiss, P. Tonino, R. van der Pijl, E. Karimi, H. Gong, et al., "Triggering typical nemaline myopathy with compound heterozygous nebulin mutations reveals myofilament structural changes as pathomechanism.", Nat Commun, vol. 11, issue 1, pp. 2699, 2020 Jun 01.
PMID: 32483185
2018
Heunks, L., and C. Ottenheijm, "Diaphragm-Protective Mechanical Ventilation to Improve Outcomes in ICU Patients?", Am J Respir Crit Care Med, vol. 197, issue 2, pp. 150-152, 2018 Jan 15.
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2017
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2016
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2015
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2014
Hooijman, P. E., M. A. Paul, G. J. M. Stienen, A. Beishuizen, H. W. H. van Hees, S. Singhal, M. Bashir, M. T. Budak, J. Morgen, R. J. Barsotti, et al., "Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation.", Am J Physiol Lung Cell Mol Physiol, vol. 307, issue 6, pp. L460-70, 2014 Sep 15.
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Hooijman, P. E., A. Beishuizen, M. C. de Waard, F. S. de Man, J. W. Vermeijden, P. Steenvoorde, A. R Bouwman, W. Lommen, H. W. H. van Hees, L. M. A. Heunks, et al., "Diaphragm fiber strength is reduced in critically ill patients and restored by a troponin activator.", Am J Respir Crit Care Med, vol. 189, issue 7, pp. 863-5, 2014 Apr 01.
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