CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
The electrogenic cardiac sodium bicarbonate co-transporter (NBCe1) contributes to the reperfusion injury
MOSCA SM; ORLOWSKI A; FANTINELLI JC; AIELLO A
ELSEVIER SCIENCE INC
Lugar: Amsterdam; Año: 2014 vol. 23 p. 224 - 230
Background: Although the participation of the electrogenic sodium/bicarbonate cotransporter (NBCe1) in therecovery from an intracellular acid load is recognized, its role in ischemia?reperfusion is still unclear.Methods and results: Our objective was to assess the role of NBCe1 in reperfusion injury. We use selectivefunctional antibodies against extracellular loop 3 (a-L3) and loop 4 (a-L4) of NBCe1. a-L3 inhibits and a-L4stimulates NBCe1 activity. Isolated rat hearts were submitted to 40 min of coronary occlusion and 1 h ofreperfusion. a-L3, a-L4 or S0859 ? selective Na+-HCO3 - co-transport inhibitor ? were administered during theinitial 10 min of reperfusion. The infarct size (IS) was measured by triphenyltetrazolium chloride stainingtechnique. Postischemic systolic and diastolic functions were also assessed. a-L3 and S0859 treatmentsdecreased significantly (Pb.05) the IS (16±3% for a-L3 vs. 32±5% in hearts treated with control nonimmuneserum and 19±3% for S0859 vs. 39±2% in untreated hearts). Myocardial function during reperfusion improvedafter a-L3 treatment, but it was not modified by S0859. The infusion of a-L4 did not modify neither the IS normyocardial function.Conclusions: TheNBCe1 hyperactivity during reperfusion leads toNa+and Ca2+ loading, conducing to Ca2+ overloadand myocardial damage. Consistently, we have shown herein that the selective NBCe1 blockade with a-L3 exertedcardioprotection. This beneficial action strongly suggests that NBCe1 could be a potential target for the treatment ofcoronary disease.