A Daniel Martin1, Anna-Marie Joseph, Thomas M Beaver, Barbara K Smith, Tomas D Martin, Kent Berg, Philip J Hess, Harsha V Deoghare, Christiaan Leeuwenburgh. 1. 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.
Abstract
OBJECTIVES: Recent 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. DESIGN: Within subjects repeated measures study. SETTING: Operating room in an academic health center. PATIENTS: Five subjects undergoing elective cardiothoracic surgery. INTERVENTIONS: In 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 RESULTS: Mitochondrial 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). CONCLUSION: These 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.
OBJECTIVES: Recent 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. DESIGN: Within subjects repeated measures study. SETTING: Operating room in an academic health center. PATIENTS: Five subjects undergoing elective cardiothoracic surgery. INTERVENTIONS: In 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 RESULTS: Mitochondrial 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). CONCLUSION: These 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.
Authors: Andrey V Kuznetsov; Vladimir Veksler; Frank N Gellerich; Valdur Saks; Raimund Margreiter; Wolfram S Kunz Journal: Nat Protoc Date: 2008 Impact factor: 13.491
Authors: Ghislaine Gayan-Ramirez; Dries Testelmans; Karen Maes; Gábor Z Rácz; Pascal Cadot; Ernö Zádor; Frank Wuytack; Marc Decramer Journal: Crit Care Med Date: 2005-12 Impact factor: 7.598
Authors: Huibin Tang; Myung Lee; Murat T Budak; Nicole Pietras; Scott Hittinger; Michael Vu; Andy Khuong; Chuong D Hoang; Sabah N A Hussain; Sanford Levine; Joseph B Shrager Journal: FASEB J Date: 2011-05-19 Impact factor: 5.191
Authors: Sabah N A Hussain; Mahroo Mofarrahi; Ioanna Sigala; Ho Cheol Kim; Theodoros Vassilakopoulos; Francois Maltais; Ion Bellenis; Rakesh Chaturvedi; Stewart B Gottfried; Peter Metrakos; Gawiyou Danialou; Stefan Matecki; Samir Jaber; Basil J Petrof; Peter Goldberg Journal: Am J Respir Crit Care Med Date: 2010-07-16 Impact factor: 21.405
Authors: Andreas N Kavazis; Erin E Talbert; Ashley J Smuder; Matthew B Hudson; W Bradley Nelson; Scott K Powers Journal: Free Radic Biol Med Date: 2009-01-13 Impact factor: 7.376
Authors: Bumsoo Ahn; Thomas Beaver; Tomas Martin; Philip Hess; Babette A Brumback; Shakeel Ahmed; Barbara K Smith; Christiaan Leeuwenburgh; A Daniel Martin; Leonardo F Ferreira Journal: Am J Respir Crit Care Med Date: 2014-10-01 Impact factor: 21.405
Authors: Marloes van den Berg; Pleuni E Hooijman; Albertus Beishuizen; Monique C de Waard; Marinus A Paul; Koen J Hartemink; Hieronymus W H van Hees; Michael W Lawlor; Lorenza Brocca; Roberto Bottinelli; Maria A Pellegrino; Ger J M Stienen; Leo M A Heunks; Rob C I Wüst; Coen A C Ottenheijm Journal: Am J Respir Crit Care Med Date: 2017-12-15 Impact factor: 21.405
Authors: Barbara K Smith; Markus S Renno; Meghan M Green; Terry M Sexton; Lee Ann Lawson; Anatole D Martin; Manuela Corti; Barry J Byrne Journal: Muscle Nerve Date: 2015-12-29 Impact factor: 3.217
Authors: Sebastien Preau; Dominique Vodovar; Boris Jung; Steve Lancel; Lara Zafrani; Aurelien Flatres; Mehdi Oualha; Guillaume Voiriot; Youenn Jouan; Jeremie Joffre; Fabrice Uhel; Nicolas De Prost; Stein Silva; Eric Azabou; Peter Radermacher Journal: Ann Intensive Care Date: 2021-07-03 Impact factor: 6.925