Intraoperative Hemi-Diaphragm Electrical Stimulation Demonstrates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients
Robert T. Mankowski,
Stephanie E. Wohlgemuth,
Guilherme Bresciani,
A. Daniel Martin,
George Arnaoutakis,
Tomas Martin,
Eric Jeng,
Leonardo Ferreira,
Tiago Machuca,
Mindaugas Rackauskas,
Ashley J. Smuder,
Thomas Beaver,
Christiaan Leeuwenburgh,
Barbara K. Smith
Affiliations
Robert T. Mankowski
Department of Physiology and Aging, University of Florida, Gainesville, FL 32611, USA
Stephanie E. Wohlgemuth
Department of Physiology and Aging, University of Florida, Gainesville, FL 32611, USA
Guilherme Bresciani
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA
A. Daniel Martin
Department of Physical Therapy, University of Florida, Gainesville, FL 32611, USA
George Arnaoutakis
Department of Surgery, University of Florida, Gainesville, FL 32611, USA
Tomas Martin
Department of Surgery, University of Florida, Gainesville, FL 32611, USA
Eric Jeng
Department of Surgery, University of Florida, Gainesville, FL 32611, USA
Leonardo Ferreira
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA
Tiago Machuca
Department of Surgery, University of Florida, Gainesville, FL 32611, USA
Mindaugas Rackauskas
Department of Surgery, University of Florida, Gainesville, FL 32611, USA
Ashley J. Smuder
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA
Thomas Beaver
Department of Surgery, University of Florida, Gainesville, FL 32611, USA
Christiaan Leeuwenburgh
Department of Physiology and Aging, University of Florida, Gainesville, FL 32611, USA
Barbara K. Smith
Department of Physical Therapy, University of Florida, Gainesville, FL 32611, USA
Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.
