Heparin improves gas exchange during experimental acute lung injury in newborn piglets
Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory d...
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Veröffentlicht in: | American journal of respiratory and critical care medicine 1998-11, Vol.158 (5), p.1620-1625 |
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description | Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02). |
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We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02).</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/ajrccm.158.5.9803041</identifier><identifier>PMID: 9817717</identifier><language>eng</language><publisher>New York, NY: American Lung Association</publisher><subject>Analysis of Variance ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Anticoagulants - administration & dosage ; Anticoagulants - therapeutic use ; Antithrombin III - administration & dosage ; Antithrombin III - therapeutic use ; Biological and medical sciences ; Disease Models, Animal ; Drug Combinations ; Emergency and intensive care: neonates and children. Prematurity. Sudden death ; Female ; Follow-Up Studies ; Heparin - administration & dosage ; Heparin - therapeutic use ; Hyalin ; Intensive care medicine ; Lung - pathology ; Male ; Medical sciences ; Oxygen - administration & dosage ; Oxygen - blood ; Pressure ; Pulmonary Gas Exchange - drug effects ; Random Allocation ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult - drug therapy ; Respiratory Distress Syndrome, Adult - pathology ; Respiratory Distress Syndrome, Adult - physiopathology ; Serine Proteinase Inhibitors - administration & dosage ; Serine Proteinase Inhibitors - therapeutic use ; Swine ; Treatment Outcome ; Ventilation-Perfusion Ratio</subject><ispartof>American journal of respiratory and critical care medicine, 1998-11, Vol.158 (5), p.1620-1625</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-ab0d3f57b55014645beb28d4e7c9867de9aaa1529a67e83118ba9fdf25c424043</citedby><cites>FETCH-LOGICAL-c331t-ab0d3f57b55014645beb28d4e7c9867de9aaa1529a67e83118ba9fdf25c424043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4025,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1593549$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9817717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ABUBAKAR, K</creatorcontrib><creatorcontrib>SCHMIDT, B</creatorcontrib><creatorcontrib>MONKMAN, S</creatorcontrib><creatorcontrib>WEBBER, C</creatorcontrib><creatorcontrib>DESA, D</creatorcontrib><creatorcontrib>ROBERTS, R</creatorcontrib><title>Heparin improves gas exchange during experimental acute lung injury in newborn piglets</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02).</description><subject>Analysis of Variance</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Anticoagulants - administration & dosage</subject><subject>Anticoagulants - therapeutic use</subject><subject>Antithrombin III - administration & dosage</subject><subject>Antithrombin III - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Disease Models, Animal</subject><subject>Drug Combinations</subject><subject>Emergency and intensive care: neonates and children. Prematurity. Sudden death</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Heparin - administration & dosage</subject><subject>Heparin - therapeutic use</subject><subject>Hyalin</subject><subject>Intensive care medicine</subject><subject>Lung - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Oxygen - administration & dosage</subject><subject>Oxygen - blood</subject><subject>Pressure</subject><subject>Pulmonary Gas Exchange - drug effects</subject><subject>Random Allocation</subject><subject>Respiration, Artificial</subject><subject>Respiratory Distress Syndrome, Adult - drug therapy</subject><subject>Respiratory Distress Syndrome, Adult - pathology</subject><subject>Respiratory Distress Syndrome, Adult - physiopathology</subject><subject>Serine Proteinase Inhibitors - administration & dosage</subject><subject>Serine Proteinase Inhibitors - therapeutic use</subject><subject>Swine</subject><subject>Treatment Outcome</subject><subject>Ventilation-Perfusion Ratio</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAQhoMofv8DhR7EW9ekSZrkKKKusOBFxVuYptPape3WpPXj3xvZoqf5eGdeZh5CzhhdMJaLK1h757oFk3ohF0ZTTgXbIYdMcpkKo-huzKniqRDm9YAchbCmlGWa0X2ybzRTiqlD8rLEAXzTJ003-M0HhqSGkOCXe4O-xqScolbHekDfdNiP0CbgphGTdor9pl9P_juGpMfPYuP7ZGjqFsdwQvYqaAOezvGYPN_dPt0s09Xj_cPN9Sp1nLMxhYKWvJKqkJIykQtZYJHpUqByRueqRAMATGYGcoWaM6YLMFVZZdKJTFDBj8nl1jce_z5hGG3XBIdtCz1upmAVpbk2XMVBsR10fhOCx8oO8SHw35ZR-4vTbnHaiNNKO-OMa-ez_1R0WP4tzfyifjHrEBy0lYfeNeHfWxouheE_Sp2AWA</recordid><startdate>19981101</startdate><enddate>19981101</enddate><creator>ABUBAKAR, K</creator><creator>SCHMIDT, B</creator><creator>MONKMAN, S</creator><creator>WEBBER, C</creator><creator>DESA, D</creator><creator>ROBERTS, R</creator><general>American Lung Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19981101</creationdate><title>Heparin improves gas exchange during experimental acute lung injury in newborn piglets</title><author>ABUBAKAR, K ; SCHMIDT, B ; MONKMAN, S ; WEBBER, C ; DESA, D ; ROBERTS, R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-ab0d3f57b55014645beb28d4e7c9867de9aaa1529a67e83118ba9fdf25c424043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Analysis of Variance</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Anticoagulants - administration & dosage</topic><topic>Anticoagulants - therapeutic use</topic><topic>Antithrombin III - administration & dosage</topic><topic>Antithrombin III - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Disease Models, Animal</topic><topic>Drug Combinations</topic><topic>Emergency and intensive care: neonates and children. Prematurity. Sudden death</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Heparin - administration & dosage</topic><topic>Heparin - therapeutic use</topic><topic>Hyalin</topic><topic>Intensive care medicine</topic><topic>Lung - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Oxygen - administration & dosage</topic><topic>Oxygen - blood</topic><topic>Pressure</topic><topic>Pulmonary Gas Exchange - drug effects</topic><topic>Random Allocation</topic><topic>Respiration, Artificial</topic><topic>Respiratory Distress Syndrome, Adult - drug therapy</topic><topic>Respiratory Distress Syndrome, Adult - pathology</topic><topic>Respiratory Distress Syndrome, Adult - physiopathology</topic><topic>Serine Proteinase Inhibitors - administration & dosage</topic><topic>Serine Proteinase Inhibitors - therapeutic use</topic><topic>Swine</topic><topic>Treatment Outcome</topic><topic>Ventilation-Perfusion Ratio</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ABUBAKAR, K</creatorcontrib><creatorcontrib>SCHMIDT, B</creatorcontrib><creatorcontrib>MONKMAN, S</creatorcontrib><creatorcontrib>WEBBER, C</creatorcontrib><creatorcontrib>DESA, D</creatorcontrib><creatorcontrib>ROBERTS, R</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ABUBAKAR, K</au><au>SCHMIDT, B</au><au>MONKMAN, S</au><au>WEBBER, C</au><au>DESA, D</au><au>ROBERTS, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heparin improves gas exchange during experimental acute lung injury in newborn piglets</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>1998-11-01</date><risdate>1998</risdate><volume>158</volume><issue>5</issue><spage>1620</spage><epage>1625</epage><pages>1620-1625</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02).</abstract><cop>New York, NY</cop><pub>American Lung Association</pub><pmid>9817717</pmid><doi>10.1164/ajrccm.158.5.9803041</doi><tpages>6</tpages></addata></record> |
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subjects | Analysis of Variance Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Anticoagulants - administration & dosage Anticoagulants - therapeutic use Antithrombin III - administration & dosage Antithrombin III - therapeutic use Biological and medical sciences Disease Models, Animal Drug Combinations Emergency and intensive care: neonates and children. Prematurity. Sudden death Female Follow-Up Studies Heparin - administration & dosage Heparin - therapeutic use Hyalin Intensive care medicine Lung - pathology Male Medical sciences Oxygen - administration & dosage Oxygen - blood Pressure Pulmonary Gas Exchange - drug effects Random Allocation Respiration, Artificial Respiratory Distress Syndrome, Adult - drug therapy Respiratory Distress Syndrome, Adult - pathology Respiratory Distress Syndrome, Adult - physiopathology Serine Proteinase Inhibitors - administration & dosage Serine Proteinase Inhibitors - therapeutic use Swine Treatment Outcome Ventilation-Perfusion Ratio |
title | Heparin improves gas exchange during experimental acute lung injury in newborn piglets |
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