Intraoperative Hemidiaphragm Stimulation Offsets Slow‐Twitch Muscle Fiber Atrophy and Contractile Dysfunction

Abstract

Prolonged mechanical ventilation induces considerable atrophy of slow‐ and fast‐twitch fibers in the human diaphragm. In pilot work, we detected early atrophy and specific force decrement in fast‐twitch fibers of patients following an average 4.6‐hour thoracic operations. We now present interim data from a larger controlled trial of diaphragm stimulation as a means to reduce slow‐ and fast‐twitch‐ fiber atrophy and metabolic derangements that occur with mechanical ventilation. We hypothesized that intraoperative hemidiaphragm would mitigate both slow‐ and fast‐twitch fiber contractile dysfunction in the human diaphragm. Twelve adults (6F, age 62 ±12 years) consented to participate in this IRB‐approved study. During cardiothoracic surgical procedures, one hemidiaphragm underwent 1 minute of electrical phrenic nerve stimulation every 30 minutes (30 twitches/minute, 1.5 milliseconds pulse duration, amplitude variable to produce a strong twitch contraction, up to 25 mA), while the contralateral hemidiaphragm remained inactive. Thirty minutes following the last stimulation bout, biopsies were obtained from both hemidiaphragms. Muscle fibers were buffered, permeabilized, and separated for evaluation of cross‐sectional area and force‐generating properties. A mixed effects model with random intercept for each subject was used to evaluate the fixed effects of stimulation and fiber type on single‐fiber force mechanics, and significance was p<0.05. Subjects underwent an average 7 ±2 hemidiaphragm stimulations at 17 ±2 mA, and biopsies were collected after 4.75 ±1.03 hours of mechanical ventilation. Cross‐sectional area of unstimulated slow‐twitch fibers was significantly smaller than stimulated slow‐twitch fibers (5632 ±349 vs 4619 ±247 μM2), with no effect on fast‐twitch fibers (5631 ±350 vs 5768 ±351 μM2), [p<0.005]. Likewise, stimulation resulted in significantly higher specific force of slow‐twitch (106 ±6 vs 97 ±6 kN/m2), but not fast‐twitch diaphragm single fibers (126 ±6 vs 130 ±6 kN/m2), [p<0.001]. Stimulation did not appreciably alter fiber calcium‐sensitivity properties of either fiber type. Our data suggest that stimulation attenuates diaphragm slow‐twitch fiber atrophy and contractile dysfunction induced by mechanical ventilation. Fiber type‐specific changes with short periods of mechanical ventilation may be attributed to predominant slow fiber recruitment during tidal breathing.Support or Funding InformationThis work was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases, award R01 AR072328