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Carbonic Anhydrase Inhibition: Effect on Rat Hearts In Vitro With and Without pH Perturbations
Author(s) -
Wasinger Nicholas A.,
Geisbuhler Timothy P.,
Brechue William F.
Publication year - 2018
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.2018.32.1_supplement.901.10
Subject(s) - preload , afterload , chemistry , contractility , medicine , cardiology , endocrinology , ventricle , hemodynamics
Myocardial force generation is modulated by stretch‐induced mechanisms. The Starling effect relates to increased force following stretch due to venous return. The Anrep effect is a change in contractility with stretch secondary to increased afterload. Both mechanisms are related to intracellular Ca 2+ dynamics. Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide (CO 2 ) which is involved in cellular acid‐base balance. In skeletal muscle in vitro , inhibition of CA leads to increased fatigue due to altered Ca 2+ handling at the sarcoplasmic reticulum. Our purpose was to investigate the role of CA in stretch‐induced change in myocardial force generation. Methods Hearts from Sprague‐Dawley rats were perfused in the working Langendorff style with Krebs‐Henseleit buffer [pH +/− 7.35 or 6.20, supplemented with 0.2 to 0.8% serum albumin (BSA)] and allowed to equilibrate 5 min under baseline preload (10 mmHg) and afterload (55 mmHg) conditions. Performance was examined at preloads of 10, 15, and 20 mmHg and constant afterload (55 mmHg); preload was then returned to 10 mmHg, and performance examined at afterloads of 55, 60, and 65 mmHg with constant preload (10 mmHg). Ethoxzolamide (Eth, 0.1 μM) or vehicle (water) was added to the perfusing buffer and the preload/afterload protocol repeated after 5 min equilibration with treatment. Systolic and diastolic pressure, heart rate, and dP/dt were monitored during the protocol. Performance was evaluated for individual parameters as a ratio of (value post‐addition)/(value pre‐addition) (hereafter called P post /P pre ). Results Colloids in the perfusing medium preserve cardiac performance by preventing tissue edema. Cardiac performance (that is, the ability of the heart to maintain output and pressure) was best preserved over 40 min using BSA=0.8% (w/v). Dropping the pH to 6.2 from 7.35 increased P post /P pre with regard to mean systolic pressure [1.04 ± 0.14 at 6.2 vs 0.47 ± 0.48 at 7.35 (p <0.05)], decreased P post /P pre for peak systolic pressure [0.97 ± 0.02 at 6.2 vs 1.05 ± 0.03 at 7.35 (p <0.05)], and decreased P post /P pre for minimum diastolic pressure [1.07 ± 0.01 at 6.2 vs 1.18 ± 0.06 at 7.35 (p <0.05)]. Addition of Eth decreased P post /P pre for peak systolic pressure [1.00 ± 0.02 at 7.35 with Eth vs 0.89 ± 0.05 at 7.35 without Eth (p <0.05)] and increased P post /P pre for minimum diastolic pressure [1.03 ± 0.05 at 7.35 with Eth vs 1.18 ± 0.06 at 7.35 without Eth (p <0.05)] at pH=7.35. Addition of Eth neither increased nor decreased P post /P pre for any performance parameter examined at pH=6.20. Conclusion CA inhibition may lead to correction of function disrupted by pH perturbation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .