Non-invasive measurement of mitochondrial oxygenation and respiration in human endotoxemia and sepsis

Presented During:

Sunday, April 29, 2018: 7:30 AM  - 9:00 AM 
Hyatt Regency Chicago Hotel  
Room: Riverside West, Exhibit Level, East Tower  

Session Number:

556 

Reference(s):

Ubbink, J. Clin. Monit. Comput. 2017 31(6):1143-1150 

Session Type:

Abstract Submissions 

Presenting Author:

Mr. Mark Wefers Bettink, MD  

Co-Author(s):

Jelle Zwaag, MD  
Mathijs Kox, PhD  
Egbert Mik, MD, PhD  
Dr. Floor Harms, MD PhD  

Submitter:

Mr. Mark Wefers Bettink, MD  

Introduction:

In vivo measurement of mitochondrial oxygen concentration (mitoPO2) and metabolism is notoriously difficult. A new and promising non-invasive method of measuring mitochondrial oxygenation and respiration in the skin is the COMET (Cellular Oxygen METabolism) monitor (1). In this study, we measured changes in mitoPO2 and the cellular oxygen disappearance rate (ODR) using the COMET monitor during endotoxin-induced systemic inflammation in humans in vivo.

Methods:

Four male subjects received 2 ng/kg lipopolysaccharide (LPS derived from Escherichia coli O:113) intravenously to elicit a systemic inflammatory response. Mean arterial pressure (MAP), heart rate, temperature and sickness score were measured up to eight hours after LPS administration. Mitochondrial respiration parameters mitoPO2 and ODR (Oxygen Disappearance Rate) were measured non-invasively with the COMET measurement system at four times points: Just prior to LPS administration and 1.45 hours, 4 hours, and 7 hours thereafter.

Results:

MitoPO2 decreased from 67 ± 9 at baseline to 37 ± 3 mmHg at 1.45 hours post-LPS (p<0.0001), and normalized afterwards as shown in FIG 1A. ODR showed a biphasic pattern, with an initial decrease at 1.45 hours after LPS compared with baseline (7.5±0.4 mmHg*s-1 vs. -6.8 ± 0.5 mmhg*s-1) and a subsequent increase at 4 and 7 hours post-LPS (-8.7 ± 1.2 and -8,9 ± 0.7 mmhg*s-1) FIG 1B. MAP initially increased (from 103±2 at baseline to 109±14 mmHg at 1.45 hours post-LPS), and subsequently decreased to 93±10 mmHg 4 hours post-LPS. Lactate remained unchanged during endotoxemia.

Conclusion:

The COMET monitor can detect changes in mitoPO2 and ODR in a relatively mild model of systemic inflammation. This study paves the way for bedside monitoring of acute alterations in mitochondrial oxygenation and respiration in patients. Recently we started measurement of mitoPO2 and ODR in patients in the intensive care patients in the Erasmus Medical Centre and expect to be able to present our first results in combination with the data of the healthy volunteers.

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Subspecialty Categories:

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