{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:17:22Z","timestamp":1761988642157},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,11,6]],"date-time":"2013-11-06T00:00:00Z","timestamp":1383696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activated matrix metalloproteinases (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>s) cause cardiomyocyte injury during acute pulmonary thromboembolism (<jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content>). However, the functional consequences of this alteration are not known. We examined whether doxycycline (a <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content> inhibitor) improves right ventricle function and the cardiac responses to dobutamine during <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> was induced with autologous blood clots (350\u00a0mg\/kg) in anaesthetized male lambs pre\u2010treated with doxycycline (Doxy, 10\u00a0mg\/kg\/day, intravenously) or saline. Non\u2010embolized control lambs received doxycycline pre\u2010treatment or saline. The responses to intravenous dobutamine (Dob, 1, 5, 10\u00a0\u03bcg\/kg\/min.) or saline infusions at 30 and 120\u00a0min. after <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> induction were evaluated by echocardiography. <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> increased mean pulmonary artery pressure and pulmonary vascular resistance index by ~185%. Doxycycline partially prevented <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content>\u2010induced pulmonary hypertension (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> diameter increased in the <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> group (from 10.7\u00a0\u00b1\u00a00.8 to 18.3\u00a0\u00b1\u00a01.6\u00a0mm, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), but not in the Doxy+<jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> group (from 13.3\u00a0\u00b1\u00a00.9 to 14.4\u00a0\u00b1\u00a01.0\u00a0mm, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05). <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> dysfunction on stress echocardiography was observed in embolized lambs (<jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content>+Dob group) but not in embolized animals pre\u2010treated with doxycycline (Doxy+<jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content>+Dob). <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> increased <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109 activity, oxidative stress and gelatinolytic activity in the <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>. Although doxycycline had no effects on <jats:styled-content style=\"fixed-case\">RV MMP<\/jats:styled-content>\u20109 activity, it prevented the increases in <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> oxidative stress and gelatinolytic activity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content> increased serum cardiac troponin I concentrations (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), doxycycline partially prevented this alteration (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). We found evidence to support that doxycycline prevents <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> dysfunction and improves the cardiac responses to dobutamine during <jats:styled-content style=\"fixed-case\">APT<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jcmm.12163","type":"journal-article","created":{"date-parts":[[2013,11,7]],"date-time":"2013-11-07T03:46:38Z","timestamp":1383795998000},"page":"1588-1597","source":"Crossref","is-referenced-by-count":13,"title":["Matrix metalloproteinase inhibition attenuates right ventricular dysfunction and improves responses to dobutamine during acute pulmonary thromboembolism"],"prefix":"10.1111","volume":"17","author":[{"given":"Evandro M.","family":"Neto\u2010Neves","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozelia","family":"Sousa\u2010Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina C.","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology State University of Campinas Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elen","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla S.","family":"Ceron","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minna M. 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