Hypoxic Preconditioning Improves Diaphragm Function via Reactive Oxygen Species Formation
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Authors
Chien, Michael T.
Issue Date
2013
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by several
deleterious alterations of the respiratory muscles, particularly the diaphragm, leading to
the excessive intracellular formation of reactive oxygen species (ROS). Hypoxic
preconditioning (HPC) therapies, however, have proven effective in protecting skeletal
diaphragm muscle from this oxidative damage. We used mice diaphragm to test the
hypothesis that HPC will be effective in reducing harmful levels of hypoxia-induced ROS
formation and consequently increase diaphragmatic force generation. Isolated diaphragm
muscle was subjected to 3, 5, or 10 cycles of acute HPC treatment (2 min of 95% N2 and
5% C02 followed by 2 min of 95% 02 and 5% C02) while living mice were treated daily
with chronic HPC (2 min of 5 Torr 02 balanced with N2 followed by 2 min of 21% 02)
over a 2-week period. Both muscle treatments were then electrically stimulated in a
COPD-like environment (95% N2 and 5% C02). Five cycles of acute HPC and chronic
HPC treatments resulted in increased diaphragmatic force generation. Ultrasound
techniques were then applied to measure diaphragm displacement and respiratory rate in
the chronic HPC model. Similarly, antioxidants ebselen and tiron were also able to rescue
muscle function. Additionally, we used several inhibitors to further elucidate upon a
possible HPC protection pathway. These results demonstrate that, in hypoxic mice
diaphragm, 1) acute and chronic HPC reduced intracellular ROS formation in contracting
skeletal muscle, 2) HPC rescued diaphragmatic force generation, and 3) Antioxidant
treatment with ebselen or tiron reduced ROS generation to baseline levels.
Description
v, 26 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.