CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Carbonic anhydrase inhibitors alleviate cardiac dysfunction after sustained coronary artery ligation in rats.
Autor/es:
VARGAS, LA; PINILLA, AO; SWENSON, ER; PEREZ, NG; ALVAREZ, BV
Reunión:
Congreso; Canadian Cardiovascular Congress; 2014
Resumen:
Background- Heart failure often results from maladaptive remodeling of the myocardium after pathological hypertrophy of the heart. While carbonic anhydrase (CA) genes are overexpressed in the hypertrophic and failing human myocardium, carbonic anhydrase inhibition prevents and reduces cardiomyocyte hypertrophy in culture models of cardiomyocytes subjected to pro-hypertrophic stimuli.  Method/Results- We aimed to test the role of the poorly membrane-permeable potent CA inhibitor, benzolamide (BZ), and the potent freely diffusible CA inhibitor ethoxzolamide (ETZ), in rats subjected to coronary artery ligation (CAL).  Wistar rats with established signs of heart failure (HF) induced by sustained (eight month) left coronary artery ligation were treated with BZ or ETZ (4 mg.kg.day-1) by a month, and had the left ventricular function and structure evaluated.  Lung weight/body weight ratio increased significantly in CAL rats, 17±1% increase compared to control, suggestive of pulmonary edema and a transition to the HF state; and this condition was ameliorated by BZ and ETZ, 9±5% and 9±8% increase respectively, compared to control.  Functional echocardiographic recordings showed decreased left ventricular midwall shortening in HF rats, 21±1% vs. control 32±1%; which was improved by BZ 29±1%, and ETZ 27±1%, treatments.  In addition, the left ventricular endocardial shortening was considerably reduced in HF rats 38±3% compared to control 62±1%, and it was partially restored by BZ 48±2%, and ETZ 46±1%.  Finally, CAL induced an increased in interstitial fibrosis which was reversed by BZ and ETZ therapy. Conclusion- We conclude that CA inhibitors with different cell permeability contribute to improve the functional remodeling of the failing heart, and this condition is accompanied by the reduction of fibrotic tissue deposition in infarcted rat hearts.
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