Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.

Thoracic surgery rapidly induces weakness in human diaphragm fibers. The dysfunction is thought to arise from combined effects of the surgical procedures and inactivity. This project tested whether brief bouts of intraoperative hemidiaphragm stimulation would mitigate slow and fast fiber loss of for...

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Main Authors: Guilherme Bresciani, Thomas Beaver, A Daniel Martin, Robbert van der Pijl, Robert Mankowski, Christiaan Leeuwenburgh, Coen A C Ottenheijm, Tomas Martin, George Arnaoutakis, Shakeel Ahmed, Vinicius M Mariani, Wei Xue, Barbara K Smith, Leonardo F Ferreira
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0320936
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author Guilherme Bresciani
Thomas Beaver
A Daniel Martin
Robbert van der Pijl
Robert Mankowski
Christiaan Leeuwenburgh
Coen A C Ottenheijm
Tomas Martin
George Arnaoutakis
Shakeel Ahmed
Vinicius M Mariani
Wei Xue
Barbara K Smith
Leonardo F Ferreira
author_facet Guilherme Bresciani
Thomas Beaver
A Daniel Martin
Robbert van der Pijl
Robert Mankowski
Christiaan Leeuwenburgh
Coen A C Ottenheijm
Tomas Martin
George Arnaoutakis
Shakeel Ahmed
Vinicius M Mariani
Wei Xue
Barbara K Smith
Leonardo F Ferreira
author_sort Guilherme Bresciani
collection DOAJ
description Thoracic surgery rapidly induces weakness in human diaphragm fibers. The dysfunction is thought to arise from combined effects of the surgical procedures and inactivity. This project tested whether brief bouts of intraoperative hemidiaphragm stimulation would mitigate slow and fast fiber loss of force in the human diaphragm. We reasoned that maintenance of diaphragm activity with brief bouts of intraoperative phrenic stimulation would mitigate diaphragm fiber weakness and myofilament protein derangements caused by thoracic surgery. Nineteen adults (9 females, age 59 ± 12 years) with normal inspiratory strength or spirometry consented to participate. Unilateral phrenic twitch stimulation (twitch duration 1.5 ms, frequency 0.5 Hz, current 2x the motor threshold, max 25 mA) was applied for one minute, every 30 minutes during cardiothoracic surgery. Thirty minutes following the last stimulation bout, biopsies were obtained from the hemidiaphragms for single fiber force mechanics and quantitation of myofilament proteins (abundance and phosphorylation) and compared by a linear mixed model and paired t-test, respectively. Subjects underwent 6 ±  2 hemidiaphragm stimulations at 17 ±  6 mA, during 278 ±  68 minutes of surgery. Longer-duration surgeries were associated with a progressive decline in diaphragm fiber force (p < 0.001). In slow-twitch fibers, phrenic stimulation increased absolute force (+25%, p <  0.0001), cross-sectional area (+16%, p < 0.0001) and specific force (+7%, p < 0.0005). Stimulation did not alter contractile function of fast-twitch fibers, calcium-sensitivity in either fiber type, and abundance and phosphorylation of myofilament proteins. In adults without preoperative weakness or lung dysfunction, unilateral phrenic stimulation mitigated diaphragm slow fiber weakness caused by thoracic surgery, but had no effect on myofilament protein abundance or phosphorylation.
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spelling doaj-art-7bdb33f3e9ea46dcbe2670f116c41fea2025-08-20T02:26:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01204e032093610.1371/journal.pone.0320936Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.Guilherme BrescianiThomas BeaverA Daniel MartinRobbert van der PijlRobert MankowskiChristiaan LeeuwenburghCoen A C OttenheijmTomas MartinGeorge ArnaoutakisShakeel AhmedVinicius M MarianiWei XueBarbara K SmithLeonardo F FerreiraThoracic surgery rapidly induces weakness in human diaphragm fibers. The dysfunction is thought to arise from combined effects of the surgical procedures and inactivity. This project tested whether brief bouts of intraoperative hemidiaphragm stimulation would mitigate slow and fast fiber loss of force in the human diaphragm. We reasoned that maintenance of diaphragm activity with brief bouts of intraoperative phrenic stimulation would mitigate diaphragm fiber weakness and myofilament protein derangements caused by thoracic surgery. Nineteen adults (9 females, age 59 ± 12 years) with normal inspiratory strength or spirometry consented to participate. Unilateral phrenic twitch stimulation (twitch duration 1.5 ms, frequency 0.5 Hz, current 2x the motor threshold, max 25 mA) was applied for one minute, every 30 minutes during cardiothoracic surgery. Thirty minutes following the last stimulation bout, biopsies were obtained from the hemidiaphragms for single fiber force mechanics and quantitation of myofilament proteins (abundance and phosphorylation) and compared by a linear mixed model and paired t-test, respectively. Subjects underwent 6 ±  2 hemidiaphragm stimulations at 17 ±  6 mA, during 278 ±  68 minutes of surgery. Longer-duration surgeries were associated with a progressive decline in diaphragm fiber force (p < 0.001). In slow-twitch fibers, phrenic stimulation increased absolute force (+25%, p <  0.0001), cross-sectional area (+16%, p < 0.0001) and specific force (+7%, p < 0.0005). Stimulation did not alter contractile function of fast-twitch fibers, calcium-sensitivity in either fiber type, and abundance and phosphorylation of myofilament proteins. In adults without preoperative weakness or lung dysfunction, unilateral phrenic stimulation mitigated diaphragm slow fiber weakness caused by thoracic surgery, but had no effect on myofilament protein abundance or phosphorylation.https://doi.org/10.1371/journal.pone.0320936
spellingShingle Guilherme Bresciani
Thomas Beaver
A Daniel Martin
Robbert van der Pijl
Robert Mankowski
Christiaan Leeuwenburgh
Coen A C Ottenheijm
Tomas Martin
George Arnaoutakis
Shakeel Ahmed
Vinicius M Mariani
Wei Xue
Barbara K Smith
Leonardo F Ferreira
Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.
PLoS ONE
title Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.
title_full Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.
title_fullStr Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.
title_full_unstemmed Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.
title_short Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.
title_sort intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery
url https://doi.org/10.1371/journal.pone.0320936
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