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Mechanical ventilation reduces rat diaphragm blood flow and impairs oxygen delivery and uptake*

Davis, Robert T. III MS; Bruells, Christian S. MD; Stabley, John N. MS; McCullough, Danielle J. MS; Powers, Scott K. PhD, EdD; Behnke, Bradley J. PhD

doi: 10.1097/CCM.0b013e31825b933a
Laboratory Investigations

Objectives: Although mechanical ventilation is a life-saving intervention in patients suffering from respiratory failure, prolonged mechanical ventilation is often associated with numerous complications including problematic weaning. In contracting skeletal muscle, inadequate oxygen supply can limit oxidative phosphorylation resulting in muscular fatigue. However, whether prolonged mechanical ventilation results in decreased diaphragmatic blood flow and induces an oxygen supply-demand imbalance in the diaphragm remains unknown.

Design: We tested the hypothesis that prolonged controlled mechanical ventilation results in a time-dependent reduction in rat diaphragmatic blood flow and microvascular PO2 and that prolonged mechanical ventilation would diminish the diaphragm’s ability to increase blood flow in response to muscular contractions.

Measurements and Main Results: Compared to 30 mins of mechanical ventilation, 6 hrs of mechanical ventilation resulted in a 75% reduction in diaphragm blood flow (via radiolabeled microspheres), which did not occur in the intercostal muscle or high-oxidative hindlimb muscle (e.g., soleus). There was also a time-dependent decline in diaphragm microvascular PO2 (via phosphorescence quenching). Further, contrary to 30 mins of mechanical ventilation, 6 hrs of mechanical ventilation significantly compromised the diaphragm’s ability to increase blood flow during electrically-induced contractions, which resulted in a ~80% reduction in diaphragm oxygen uptake. In contrast, 6 hrs of spontaneous breathing in anesthetized animals did not alter diaphragm blood flow or the ability to augment flow during electrically-induced contractions.

Conclusions: These new and important findings reveal that prolonged mechanical ventilation results in a time-dependent decrease in the ability of the diaphragm to augment blood flow to match oxygen demand in response to contractile activity and could be a key contributing factor to difficult weaning. Although additional experiments are required to confirm, it is tempting to speculate that this ventilator-induced decline in diaphragmatic oxygenation could promote a hypoxia-induced generation of reactive oxygen species in diaphragm muscle fibers and contribute to ventilator-induced diaphragmatic atrophy and contractile dysfunction.

Supplemental Digital Content is available in the text.

From the Department of Applied Physiology and Kinesiology (RTD, JNS, DJM, SKP, BJB) Center for Exercise Science, University of Florida, Gainesville, FL; and Department of Anesthesiology (CSB), Aachen University Hospital of the Rhenish-Westphalian Technical University, Aachen, Germany.

*See also p. 2914.

Mr. Davis, Dr. Bruells, and Dr. Behnke contributed equally to this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

This work was funded by NIH National Institutes of Health (AG-31317: BJB and HL-087839: SKP) and the Florida Biomedical Research Program (1BN-02; BJB). Dr. Bruells was funded by the Deutsche Forschungsgemeinschaft (BR 3998/1-1).

The authors have not disclosed any potential conflicts of interest.

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© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins