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The Diaphragm Challenged by Acid‐Base Imbalance
Author(s) -
Fitzgerald Robert,
Howell Sandra,
Roussos Charis
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.660.5
Subject(s) - chemistry , acidosis , medicine , endocrinology , endoplasmic reticulum , biophysics , metabolic acidosis , respiratory system , respiratory acidosis , biochemistry , biology
Respiratory and Metabolic Acidosis can result from a variety of diseases and be sensed by receptors in the respiratory control system. But acid/base imbalance also directly affects the performance of the principal muscle of respiration, the diaphragm (D). In this presentation we provide an overview of the in vitro (rat) and in vivo (dog) D responses to four challenges: Uncompensated/Compensated respiratory acidosis (HC/CHC) and Uncompensated/Compensated Metabolic Acidosis (MA/CMA). Our findings revealed that HC reduced the force of tetanic contraction (FC) in both rat and dog Ds. This phenomenon is often seen in human subjects as well. CHC also reduced the FC of the rat D but less that HC. Both MA and CMA reduced the FC in both rat and dog Ds. We found decreases in FC are due to decreases in peak twitch tensions and increases in ½ relaxation time (1/2RT). We found that in the rat D neither HC, MA, nor CMA reduced ATP or PCr. Further, we found that methylxanthines, neostigmine, isoproterenol acted to attenuate the decreases in FC, each by different mechanisms. But first a glance at how decreased pH i per se can affect striated muscle: (1)Increased binding of Ca ++ by the sarcoplasmic reticulum (SR) and decreased rate of Ca ++ uptake and release per impulse. The first would prolong twitch ½ RT. (2)ATPase activity is decreased and Ca ++ concentration requirement for myofibril activation is increased. (3) K + leaks from the cell, hyperpolarizing the cell and reducing membrane excitability. This work was performed when S. Howell and Ch. Roussos were at Meakins‐Christie Laboratories, McGill University. Support: NIH (HL RO1‐50712‐14; MRC, Canada, Quebec Thoracic Society.