Carbonic Anhydrase Inhibition Does Not Impact Force Generation or Fatigue Following Sustained Voluntary Maximal Isometric Contractions
Authors: Kinney Kade E. , Robbins G. Barry , Brechue William F. 
Published: June 2021

Background

Previously we observed a two‐phase decline in force generation during sustained maximal voluntary isometric contractions (MVIC) suggestive of impaired Ca2+ kinetics. Carbonic anhydrase inhibition (CAI) increases fatigue in vitro due to altered Ca2+ kinetics. CAI impairs sensory transmission in vivo, which could also impact fatigue. Our purpose was to investigate the muscle activation and fatigue response during sustained MVIC in vivo following CAI.

Methods

Following provision of informed consent to participate in this University approved study, men (n=9) performed two bouts (B1, B2) of sustained handgrip MVICs preceded/followed by 10‐min recovery periods, with and without acetazolamide (A); CA inhibitor. Using repeated measures, randomized, crossover design, A (250 mg) or placebo were ingested 14, 8, and 2 hours prior to contractions. HR (Lead II ECG) and BP (auscultation) were collected throughout the 35‐minute experiment. Force (dynamometer) and surface EMG from the brachioradialis (BR), flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), and flexor digitorum profundus (FDP) were collected continuously (1000 Hz) during bouts. sEMG signals were band pass filtered, rectified, and integrated (iEMG).

Results

Body weight (C: 87.3±18.6; A: 86.3±18.3 kg) decreased and urine pH (C: 5.57±0.43; A: 7.56±0.20) increased with A. Resting HR (C: 60±11; A: 60±10 b.min−1) and BP (C: 119±6/75±5; A: 120±7/75±6) were similar. Isometric force declined similarly in B1 and B2 respectively (C:76 and 81%; A:79 and 78%); yet B2 initial force was less than B1 (21%) with A. Fatigue progressed in two‐phases; fast phase (C B1: y=−0.38x+25.1 kg; A B1: y=−0.41x+26.8 kg; C B2: y=−0.28x+23.1 kg; A B2: y=−0.25+20.4 kg) and slow phase (C B1: y=−0.05x+11.2 kg; A B1: y=−0.06x+12.9 kg; C B2: y=−0.04x+9.9 kg; A B2: y=−0.03x+8.1 kg) were similar in B1 and B2. Slow‐phase inflection occurred at 45‐sec during B1 and 60‐sec during B2 in both treatments. Muscle activation (iEMG) showed a similar biphasic reduction in A (BR: 84%; FCR: 72%; FCU: 76%; FDP: 75%) and C (BR: 80%; FCR: 62%; FCU: 70%; FDP: 72%), as over 70% of this reduction was expressed in the initial 30–45 sec of B1. iEMG during B2 showed a similar pattern of decrease in both conditions. HR and BP increased rapidly during each bout and returned to pre‐contraction levels by 1‐min post contraction; this response was not altered by A.

Conclusions

In agreement with previous studies, A resulted in typical loss of body weight and elevated urine pH presumably due to increased urine output and Na+ excretion. CAI had no effect on initial force generation, muscle activation (iEMG), or fatigue response. The reduced recovery of force without a change in iEMG prior to B2 indicates that CAI may impact both feedback inhibition and recovery of excitation‐contraction following the initial bout.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.