{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T09:56:08Z","timestamp":1771062968138,"version":"3.50.1"},"reference-count":61,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/501100003074","name":"Ministry of Science, Technology and Productive Innovation, Argentina | Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (National Agency for Science and Technology, Argentina)","doi-asserted-by":"publisher","award":["PICT 2013 N\u00ba 01976"],"award-info":[{"award-number":["PICT 2013 N\u00ba 01976"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:p> During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CAs) leads to myocardial intracellular Ca<jats:sup>2+<\/jats:sup> increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I\/R). Langendorff-perfused isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts were treated with BZ (5 \u03bcM) during the initial 10 min of reperfusion or perfused with acid solution (AR, pH 6.4) during the first 3 min of reperfusion. p38MAPK, a kinase linked to membrane transporters and involved in cardioprotection, was examined in hearts treated with BZ in presence of the p38MAPK inhibitor SB202190 (10 \u03bcM). Infarct size (IZ) and myocardial function were assessed, and phosphorylated forms of p38MAPK, Akt, and PKC\u03b5 were evaluated by immunoblotting. We determined the rate of intracellular pH (pH<jats:sub>i<\/jats:sub>) normalization after transient acid loading in the absence and presence of BZ or BZ + SB202190 in heart papillary muscles (HPMs). Mitochondrial membrane potential (\u0394\u03a8<jats:sub>m<\/jats:sub>), Ca<jats:sup>2+<\/jats:sup> retention capacity and Ca<jats:sup>2+<\/jats:sup>-mediated swelling after I\/R were also measured. BZ, similarly to AR, reduced IZ, improved postischemic recovery of myocardial contractility, increased phosphorylation of Akt, PKC\u03b5, and p38MAPK, and normalized \u0394\u03a8<jats:sub>m<\/jats:sub> and Ca<jats:sup>2+<\/jats:sup> homeostasis, effects abolished after p38MAPK inhibition. In HPMs, BZ slowed pH<jats:sub>i<\/jats:sub> recovery, an effect that was restored after p38MAPK inhibition. We conclude that prolongation of acidic conditions during reperfusion by BZ could be responsible for the cardioprotective benefits of reduced infarction and better myocontractile function, through p38MAPK-dependent pathways. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Carbonic anhydrase inhibition by benzolamide (BZ) maintains acidity, decreases infarct size, and improves postischemic myocardial dysfunction in ischemia-reperfusion (I\/R) hearts. Protection afforded by BZ mimicked the beneficial effects elicited by an acidic solution (AR). Increased phosphorylation of p38MAPK occurs in I\/R hearts reperfused with BZ or with AR. Mitochondria from I\/R hearts possess abnormal Ca<jats:sup>2+<\/jats:sup> handling and a more depolarized membrane potential compared with control hearts, and these changes were restored by treatment with BZ or AR. <\/jats:p>","DOI":"10.1152\/japplphysiol.00957.2017","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T02:40:39Z","timestamp":1514169639000},"page":"340-352","source":"Crossref","is-referenced-by-count":18,"title":["Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury"],"prefix":"10.1152","volume":"125","author":[{"given":"Alejandro","family":"Ciocci Pardo","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares CIC-CONICET, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata, La Plata, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina 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