Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats

<b>Background</b>: Two potent carbonic anhydrase (CA) inhibitors with widely differing membrane permeability, poorly diffusible benzolamide (BZ), and highly diffusible ethoxzolamide (ETZ) were assessed to determine whether they can reduce cardiac dysfunction in rats subjected to coronary...

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Autores principales: Vargas, Lorena Alejandra, Pinilla, Oscar Andrés, Díaz, Romina Gisel, Sepúlveda, Diana Elizabeth, Swenson, Erik R., Pérez, Néstor Gustavo, Álvarez, Bernardo Víctor
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2016
Materias:
Ciencias Médicas
Carbonic anhydrase inhibitors
Heart failure
Intracellular pH
Myocardial infarction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/104723
http://hdl.handle.net/11336/50094
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-104723
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Carbonic anhydrase inhibitors
Heart failure
Intracellular pH
Myocardial infarction
spellingShingle Ciencias Médicas
Carbonic anhydrase inhibitors
Heart failure
Intracellular pH
Myocardial infarction
Vargas, Lorena Alejandra
Pinilla, Oscar Andrés
Díaz, Romina Gisel
Sepúlveda, Diana Elizabeth
Swenson, Erik R.
Pérez, Néstor Gustavo
Álvarez, Bernardo Víctor
Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
topic_facet Ciencias Médicas
Carbonic anhydrase inhibitors
Heart failure
Intracellular pH
Myocardial infarction
description <b>Background</b>: Two potent carbonic anhydrase (CA) inhibitors with widely differing membrane permeability, poorly diffusible benzolamide (BZ), and highly diffusible ethoxzolamide (ETZ) were assessed to determine whether they can reduce cardiac dysfunction in rats subjected to coronary artery ligation (CAL)-induced myocardial infarction. <b>Methods and results</b>: Rats with evidence of heart failure (HF) at 32 weeks following a permanent left anterior coronary artery occlusion were treated with placebo, BZ, or ETZ (4 mg kg day<sup>−1</sup>) for 4 weeks at which time left ventricular function and structure were evaluated. Lung weight/body weight (LW/BW) ratio increased in CAL rats by 17±1% vs. control, suggesting pulmonary edema. There was a trend for BZ and ETZ to ameliorate the increase in LW/BW by almost 50% (9±5% and 9±8%, respectively, versus CAL) (P=.16, NS). Echocardiographic assessment showed decreased left ventricular midwall shortening in HF rats, 21±1% vs. control 32±1%, which was improved by BZ to 29±1% and ETZ to 27±1%, and reduced endocardial shortening in HF rats 38±3% vs. control 62±1%, partially restored by BZ and ETZ to ~50%. Expression of the hypoxia-inducible membrane-associated CAIX isoform increased by ~60% in HF rat hearts, and this effect was blocked by ETZ. <b>Conclusions</b>: We conclude that CAL-induced myocardial interstitial fibrosis and associated decline in left ventricular function were diminished with BZ or ETZ treatment. The reductions in cardiac remodeling in HF with both ETZ and BZ CA inhibitors suggest that inhibition of a membrane-bound CA appears to be the critical site for this protection.
format Articulo
Preprint
author Vargas, Lorena Alejandra
Pinilla, Oscar Andrés
Díaz, Romina Gisel
Sepúlveda, Diana Elizabeth
Swenson, Erik R.
Pérez, Néstor Gustavo
Álvarez, Bernardo Víctor
author_facet Vargas, Lorena Alejandra
Pinilla, Oscar Andrés
Díaz, Romina Gisel
Sepúlveda, Diana Elizabeth
Swenson, Erik R.
Pérez, Néstor Gustavo
Álvarez, Bernardo Víctor
author_sort Vargas, Lorena Alejandra
title Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
title_short Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
title_full Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
title_fullStr Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
title_full_unstemmed Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
title_sort carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/104723
http://hdl.handle.net/11336/50094
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