Non-invasive monitoring of mitochondrial oxygenation and respiration in critical illness using a novel technique

Introduction: 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 (mitoPO<inf>2</inf>) 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. MitoPO<inf>2</inf> and ODR were measured by means of the protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT). Kinetic aspects of the drop in mitoPO<inf>2</inf> were recorded during 60s of skin compression. ODR was derived from the slope of the mitoPO<inf>2</inf> 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, mitoPO<inf>2</inf> 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 mitoPO<inf>2</inf> 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. Conclusion: 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.

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