• A Daniel Martin, Anna-Marie Joseph, Thomas M Beaver, Barbara K Smith, Tomas D Martin, Kent Berg, Philip J Hess, Harsha V Deoghare, and Christiaan Leeuwenburgh.
• 1Department of Physical Therapy, University of Florida, Gainesville, FL. 2Department of Aging and Geriatric Research, University of Florida, Gainesville, FL. 3Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, Gainesville, FL. 4Department of Anesthesiology, University of Florida, Gainesville, FL. 5Department of Physical Therapy, California State University, Fresno, CA.
• Crit. Care Med. 2014 Feb 1; 42 (2): e152-6.

ObjectivesRecent studies have shown that brief periods of mechanical ventilation in animals and humans can lead to ventilator-induced diaphragmatic dysfunction, which includes muscle atrophy, reduced force development, and impaired mitochondrial function. Studies in animal models have shown that short periods of increased diaphragm activity during mechanical ventilation support can attenuate ventilator-induced diaphragmatic dysfunction but corresponding human data are lacking. The purpose of this study was to examine the effect of intermittent diaphragm contractions during cardiothoracic surgery, including controlled mechanical ventilation, on mitochondrial respiration in the human diaphragm.DesignWithin subjects repeated measures study.SettingOperating room in an academic health center.PatientsFive subjects undergoing elective cardiothoracic surgery.InterventionsIn patients (age 65.6 ± 6.3 yr) undergoing cardiothoracic surgery, one phrenic nerve was stimulated hourly (30 pulses/min, 1.5 msec duration, 17.0 ± 4.4 mA) during the surgery. Subjects received 3.4 ± 0.6 stimulation bouts during surgery. Thirty minutes following the last stimulation bout, samples of diaphragm muscle were obtained from the anterolateral costal regions of the stimulated and inactive hemidiaphragms.Measurements And Main ResultsMitochondrial respiration was measured in permeabilized muscle fibers with high-resolution respirometry. State III mitochondrial respiration rates (pmol O2/s/mg wet weight) were 15.05 ± 3.92 and 11.42 ± 2.66 for the stimulated and unstimulated samples, respectively (p < 0.05). State IV mitochondrial respiration rates were 3.59 ± 1.25 and 2.11 ± 0.97 in the stimulated samples and controls samples, respectively (p < 0.05).ConclusionThese are the first data examining the effect of intermittent contractions on mitochondrial respiration rates in the human diaphragm following surgery/mechanical ventilation. Our results indicate that very brief periods (duty cycle ~1.7%) of activity can improve mitochondrial function in the human diaphragm following surgery/mechanical ventilation.

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