B3: Hyperoxia after hemorrhagic shock with pre-existing atherosclerosis

PI: P. Radermacher

While “early” mortality (i.e. < 24-48 hours) after traumatic-hemorrhagic shock is due to brain trauma or un-controllable hemorrhage, “late” (i.e. > 48 hours) mortality is mostly caused by multi-organ failure (MOF) resulting from systemic hyper-inflammation. This systemic inflammatory response is triggered by the direct physical trauma per se as well as by tissue hypoxia induced by blood loss and impaired tissue perfusion. Moreover, restoration of tissue perfusion after trauma and hemorrhage mirrors ischemia/reperfusion injury and may thus further aggravate hyper-inflammation due to increased oxidative and nitrosative stress. Patients with atherosclerosis are characterized by chronic inflammation and oxidative stress, and have at least a two times higher risk of post-traumatic MOF. Consequently, maintenance of cellular O2-supply and ATP-homoeostasis to limit the inflammatory response is of particular importance in the management of trauma and hemorrhage in these patients.  Ventilation with 100 % O2 can counteract tissue hypoxia and thereby attenuate the inflammatory response. However, this therapeutic strategy may have deleterious side effects: Pure O2 breathing may cause oxidative and nitrosative stress due to enhanced formation of reactive oxygen and nitrogen species.  Equivocal results are available on the effects of ventilation with 100 % O2 during the acute phase of shock, inasmuch both attenuated and aggravated organ dysfunction were reported. However, so far no data at all are available on the impact of pre-existing atherosclerosis during resuscitation of hemorrhagic shock using ventilation with 100 % O2. Therefore, the aim of this project is to test the hypothesis whether pure O2 ventilation attenuates organ injury after long-term, resuscitated hemorrhagic shock in swine with pre-existing atherosclerosis.  Uncoupling of the mitochondrial respiratory chain resulting from oxidative and nitrosative stress function is referred to as a central pathophysiological mechanism of the development of MOF, and therefore we hypothesize that any therapeutic effect of pure O2 ventilation is due to better maintenance of mitochondrial function.


The specific hypotheses are: 

  • H1: Pre-existing arteriosclerosis aggravates hemorrhage-induced kidney and left heart dysfunction and histological damage. 
  • H2: Ventilation with 100 % O2 during the early resuscitation Period after hemorrhagic shock attenuates organ dysfunction and histological damage.
  • H3: Pure O2 ventilation-related improvement of kidney and heart function is due to maintenance of mitochondrial respiration.

 

 

 

Video

Projektleiter

Prof. Dr. med. Dr. h.c. Peter Radermacher
Universitätsklinikum Ulm
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung (APV)
Zentrum für Biomedizinische Forschung (ZBF)    
Helmholtzstr. 8/1
89081 Ulm
Tel.: +49 731 500 60214
Fax: +49 731 500 60162
peter.radermacher(at)uni-ulm.de