title: Non-invasive monitoring of mitochondrial oxygenation and respiration in critical illness using a novel technique.
abstract: BACKGROUND
  Although mitochondrial dysfunction is proposed to be involved in the pathophysiology of sepsis, conflicting results are reported. Variation in methods used to assess mitochondrial function might contribute to this controversy. A non-invasive method for monitoring mitochondrial function might help overcome this limitation. Therefore, this study explores the possibility of in vivo monitoring of mitochondrial oxygen tension (mitoPO2) and local mitochondrial oxygen consumptionin in an endotoxin-induced septic animal model.
  
  
  METHODS
  Animals (rats n = 28) were assigned to a control group (no treatment), or to receive lipopolysaccharide without fluid resuscitation (LPS-NR) or lipopolysaccharide plus fluid resuscitation (LPS-FR). Sepsis was induced by intravenous LPS injection (1.6 mg/kg during 10 min), fluid resuscitation was performed by continuous infusion of a colloid solution, 7 ml kg(-1) h(-1) and a 2-ml bolus of the same colloid solution. MitoPO2 and ODR were measured by means of the protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT). Kinetic aspects of the drop in mitoPO2 were recorded during 60s of skin compression. ODR was derived from the slope of the mitoPO2 oxygen disappearance curve. Measurements were made before and 3 h after induction of sepsis.
  
  
  RESULTS
  At baseline (t0) all rats were hemodynamically stable. After LPS induction (t1), significant (p < 0.05) hemodynamic changes were observed in both LPS groups. At t0, mitoPO2 and ODR were 59 ± 1 mmHg, 64 ± 3 mmHg, 68 ± 4 mmHg and 5.0 ± 0.3 mmHg s(-1), 5.3 ± 0.5 mmHg s(-1), 5.7 ± 0.5 mmHg s(-1) in the control, LPS-FR and LPS-NR groups, respectively; at t1 these values were 58 ± 5 mmHg, 50 ± 2.3 mmHg, 30 ± 3.3 mmHg and 4.5 ± 0.5 mmHg s(-1), 3.3 ± 0.3 mmHg s(-1), 1.8 ± 0.3 mmHg s(-1), respectively. At t1, only mitoPO2 showed a significant difference between the controls and LPS-NR. In contrast, at t1 both LPS groups showed a significantly lower ODR compared to controls.
  
  
  CONCLUSIONS
  These data show the feasibility to monitor alterations in mitochondrial oxygen consumption in vivo by PpIX-TSLT in a septic rat model. These results may contribute to the development of a clinical device to monitor mitochondrial function in the critically ill.
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Anesthesiology, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. f.harms@erasmusmc.nl.
authors.forename: Floor A
authors.initials: FA
authors.lastname: Harms
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Anesthesiology, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. s.bodmer@erasmusmc.nl.
authors.forename: Sander I A
authors.initials: SI
authors.lastname: Bodmer
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Anesthesiology, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. n.raat@erasmusmc.nl.
authors.forename: Nicolaas J H
authors.initials: NJ
authors.lastname: Raat
authors.affiliation: Department of Anesthesiology, Laboratory of Experimental Anesthesiology, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. e.mik@erasmusmc.nl.|Department of Intensive Care, Erasmus University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. e.mik@erasmusmc.nl.
authors.forename: Egbert G
authors.initials: EG
authors.lastname: Mik
mesh_terms: D000818:Animals; D016638:Critical Illness; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008991:Monitoring, Physiologic / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D012119:Respiration; D018805:Sepsis / Q000628:therapy
chemical_list: D008070:Lipopolysaccharides; D010100:Oxygen