人工呼吸器管理と横隔膜機能不全

人工呼吸器管理では横隔膜の機能不全と萎縮を生じるというラットでの動物実験を紹介します。

Hudson, Matthew B, et al: Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy. Critical Care Medicine: April 2012 - Volume 40 - Issue 4 - p 1254–1260, doi: 10.1097/CCM.0b013e31823c8cc9

以前の研究でcontrolled mechanical ventilation（調節呼吸）によって、横隔膜の活動性が低下して、収縮機能障害と筋繊維萎縮で横隔膜の筋力低下が生じることがわかっています。

今回は、pressure support ventilation（圧サポート）では調節呼吸より、横隔膜の機能低下を少なくすることができるという仮説を検証するために動物実験を行いました。結果ですが、両者とも酸化ストレスと蛋白分解の活性化によって、横隔膜の機能低下を認めました。

ヒトでの研究ではないのでヒトでは該当しないかもしれませんが、人工呼吸器管理では横隔膜のサルコペニア（広義）が進む可能性があります。加齢、廃用、飢餓、疾患のすべての要素が重なり、呼吸筋のサルコペニアを認め、離脱困難となることも少なくないのではと思います。

Abstract
Objectives: Previous workers have demonstrated that controlled mechanical ventilation results in diaphragm inactivity and elicits a rapid development of diaphragm weakness as a result of both contractile dysfunction and fiber atrophy. Limited data exist regarding the impact of pressure support ventilation, a commonly used mode of mechanical ventilation—that permits partial mechanical activity of the diaphragm—on diaphragm structure and function. We carried out the present study to test the hypothesis that high-level pressure support ventilation decreases the diaphragm pathology associated with CMV.

Methods: Sprague-Dawley rats were randomly assigned to one of the following five groups:1) control (no mechanical ventilation); 2) 12 hrs of controlled mechanical ventilation (12CMV); 3) 18 hrs of controlled mechanical ventilation (18CMV); 4) 12 hrs of pressure support ventilation (12PSV); or 5) 18 hrs of pressure support ventilation (18PSV).

Measurements and Main Results: We carried out the following measurements on diaphragm specimens: 4-hydroxynonenal—a marker of oxidative stress, active caspase-3 (casp-3), active calpain-1 (calp-1), fiber type cross-sectional area, and specific force (sp F). Compared with the control, both 12PSV and 18PSV promoted a significant decrement in diaphragmatic specific force production, but to a lesser degree than 12CMV and 18CMV. Furthermore, 12CMV, 18PSV, and 18CMV resulted in significant atrophy in all diaphragm fiber types as well as significant increases in a biomarker of oxidative stress (4-hydroxynonenal) and increased proteolytic activity (20S proteasome, calpain-1, and caspase-3). Furthermore, although no inspiratory effort occurs during controlled mechanical ventilation, it was observed that pressure support ventilation resulted in large decrement, approximately 96%, in inspiratory effort compared with spontaneously breathing animals.

Conclusions: High levels of prolonged pressure support ventilation promote diaphragmatic atrophy and contractile dysfunction. Furthermore, similar to controlled mechanical ventilation, pressure support ventilation-induced diaphragmatic atrophy and weakness are associated with both diaphragmatic oxidative stress and protease activation. (Crit Care Med 2012; 40:–1260)