The electrogenic cardiac sodium bicarbonate co-transporter (NBCe1) contributes to the reperfusion injury.
BACKGROUND
Although the participation of the electrogenic sodium/bicarbonate cotransporter (NBCe1) in the recovery from an intracellular acid load is recognized, its role in ischemia-reperfusion is still unclear.


RESULTS
Our objective was to assess the role of NBCe1 in reperfusion injury. We use selective functional antibodies against extracellular loop 3 (a-L3) and loop 4 (a-L4) of NBCe1. a-L3 inhibits and a-L4 stimulates NBCe1 activity. Isolated rat hearts were submitted to 40 min of coronary occlusion and 1 h of reperfusion. a-L3, a-L4 or S0859--selective Na(+)-HCO3(-) co-transport inhibitor--were administered during the initial 10 min of reperfusion. The infarct size (IS) was measured by triphenyltetrazolium chloride staining technique. Postischemic systolic and diastolic functions were also assessed. a-L3 and S0859 treatments decreased significantly (P < .05) the IS (16 ± 3% for a-L3 vs. 32 ± 5% in hearts treated with control nonimmune serum and 19 ± 3% for S0859 vs. 39 ± 2% in untreated hearts). Myocardial function during reperfusion improved after a-L3 treatment, but it was not modified by S0859. The infusion of a-L4 did not modify neither the IS nor myocardial function.


CONCLUSIONS
The NBCe1 hyperactivity during reperfusion leads to Na(+) and Ca(2+) loading, conducing to Ca(2+) overload and myocardial damage. Consistently, we have shown herein that the selective NBCe1 blockade with a-L3 exerted cardioprotection. This beneficial action strongly suggests that NBCe1 could be a potential target for the treatment of coronary disease.
Established Investigator of CONICET, Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina.
Juliana C
JC
Fantinelli
Fellowship of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina.
Alejandro
A
Orlowski
Established Investigator of CONICET, Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina.
Ernesto A
EA
Aiello
Established Investigator of CONICET, Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina. Electronic address: smosca@med.unlp.edu.ar.
Susana M
SM
Mosca
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D027982:Sodium-Bicarbonate Symporters / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D016277:Ventricular Function, Left
D001549:Benzamides; D002316:Cardiotonic Agents; C528718:S 0859 compound; C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters; D013449:Sulfonamides
Infarct size; Ischemia–Reperfusion; NBCe1; NBCe1 antibodies; S0859