{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:34:32Z","timestamp":1784568872099,"version":"3.55.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,7,27]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (n=3); CPB (n=5), femoral-femoral hypothermic bypass for 1 hour; LPS (n=7), sham bypass followed by infusion of low-dose\n            <jats:italic>Escherichia coli<\/jats:italic>\n            lipopolysaccharide (LPS; 1 \u03bcg\/kg); CPB+LPS (n=6), both insults; and CPB+LPS+CMT-3 (n=5), both insults plus intravenous CMT-3 dosed to obtain a 25-\u03bcmol\/L blood concentration. CPB+LPS caused severe lung injury, as demonstrated by a significant fall in Pa\n            <jats:sc>o<\/jats:sc>\n            <jats:sub>2<\/jats:sub>\n            and an increase in intrapulmonary shunt compared with all groups (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors.\n          <\/jats:p>","DOI":"10.1161\/01.cir.100.4.400","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"400-406","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Matrix Metalloproteinase Inhibitor Prevents Acute Lung Injury After Cardiopulmonary Bypass"],"prefix":"10.1161","volume":"100","author":[{"given":"David E.","family":"Carney","sequence":"first","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Lutz","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"Picone","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis A.","family":"Gatto","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. S.","family":"Ramamurthy","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne M.","family":"Golub","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanford R.","family":"Simon","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Searles","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Paskanik","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Snyder","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Finck","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.","family":"Schiller","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary F.","family":"Nieman","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery and Cardiovascular Perfusion, SUNY Health Science Center at Syracuse; the Department of Oral Biology and Pathology, SUNY Health Science Center at Stony Brook (N.S.R., L.M.G., S.R.S.); and the Department of Biology, SUNY at Cortland (L.A.G.), NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.110.1.273"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/144.2.251"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Milberg JA Davis DR Steinberg KP Hudson D. 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