CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Post-ischemic mitochondrial state: role of electrogenic Na+/HCO3- cotransporter and carbonic anhydrase
Autor/es:
ALEJANDRO CIOCCI PARDO
Lugar:
Río de Janeiro
Reunión:
Simposio; IUPS 38th WORD CONGRESS; 2017
Resumen:
During ischemic period increased anaerobic glycolysis results in the accumulation of H+ and a large reduction of intracellular pH (pHi). The activation of alkalizing mechanisms, including the Na+- CO3- co-transporter (NBC) which is associated to carbonic anhydrase (CA), leads to intracellular Na+ increase and a subsequent Ca2+ overload. That phenomenon occurs through the activation of the Na+?Ca2+ exchanger in the reverse mode among other mechanisms. This event is a critical determinant of mitochondria dysfunction occurring during ischemia-reperfusion (I/R). Our objective was to determine the action of CA blockade with benzolamide (BZ) on alterations induced by 30-min global ischemia and 60-min reperfusion in isolated and perfused rat heart. BZ was administered at initial 10 min of reperfusion. At the end of reperfusion period the infarct size (IS), the post-ischemic myocardial function, the mitochondrial state (membrane potential, Ca2+-mediated swelling, Ca2+ retention capacity) and dynamics (the expression of different regulatory proteins such as Ser637Drp1, Mnf2, OPA1 and photographs of electronic microscope) were evaluated. To assess if BZ is able to modify the NBC activity, the restoration of pHi post transient acidosis (induced by an ammonium prepulse) was measured in isolated papillary muscles from the left ventricle.The results show that BZ decreased the IS and improved the post-ischemic recovery of contractility and the mitochondrial state and dynamics. Thus, a lesser depolarization, a greater Ca2+ response and retention capacity, a lesser expression of Ser637Drp1 were detected in hearts treated with BZ. Mitochondrial ultrastructure was near to normal after BZ treatment. Also, a lesser velocity of pHi restoration was obtained by BZ. When BZ was administered in presence of SB202190, a p38-mitogen-activated protein kinase (p38MAPK) inhibitor, these beneficial effects were partially annulled. Our results demonstrate in isolated rat heart that the selective CA blockade with BZ protects to the cardiac tissue and mitochondria against I/R injury and decreases the post-acidosis pHi recovery. These effects appear p38MAPK-mediated and suggest that a diminution of NBC activity is taking place after BZ.