Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone
Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy. Male Wistar rats were random...
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| Veröffentlicht in: | The Journal of surgical research 2006-12, Vol.136 (2), p.209-218 |
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| creator | Kume, Makoto Banafsche, Ramin Yamamoto, Yuzo Yamaoka, Yoshio Nobiling, Rainer Gebhard, Martha-Maria Klar, Ernst |
| description | Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy.
Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively.
In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls.
The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning. |
| doi_str_mv | 10.1016/j.jss.2006.05.038 |
| format | Article |
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Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively.
In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls.
The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2006.05.038</identifier><identifier>PMID: 17045613</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors ; Animals ; Blood Pressure ; Cell Communication - drug effects ; Cell Survival - drug effects ; cyclic AMP ; Cyclic AMP - metabolism ; Cyclic GMP - metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 3 ; Endothelial Cells - cytology ; Heart Rate ; Hematocrit ; ischemia-reperfusion injury ; ischemic pre-conditioning ; Ischemic Preconditioning - methods ; Leukocytes - cytology ; Liver - blood supply ; Liver - cytology ; Liver - metabolism ; Liver Circulation - drug effects ; Liver Transplantation ; Male ; microcirculation ; Microcirculation - drug effects ; Microscopy, Video ; Milrinone - pharmacology ; Nitric Oxide - metabolism ; phosphodiesterase inhibitor ; Phosphodiesterase Inhibitors - pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury - drug therapy ; Reperfusion Injury - prevention & control ; Venules - drug effects</subject><ispartof>The Journal of surgical research, 2006-12, Vol.136 (2), p.209-218</ispartof><rights>2006 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-2a3fc2bcb073aaaaf2bd6146951a72c7b7035660d7e4812aafe840b86074318f3</citedby><cites>FETCH-LOGICAL-c417t-2a3fc2bcb073aaaaf2bd6146951a72c7b7035660d7e4812aafe840b86074318f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jss.2006.05.038$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17045613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kume, Makoto</creatorcontrib><creatorcontrib>Banafsche, Ramin</creatorcontrib><creatorcontrib>Yamamoto, Yuzo</creatorcontrib><creatorcontrib>Yamaoka, Yoshio</creatorcontrib><creatorcontrib>Nobiling, Rainer</creatorcontrib><creatorcontrib>Gebhard, Martha-Maria</creatorcontrib><creatorcontrib>Klar, Ernst</creatorcontrib><title>Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy.
Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively.
In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls.
The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning.</description><subject>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors</subject><subject>Animals</subject><subject>Blood Pressure</subject><subject>Cell Communication - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>cyclic AMP</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic GMP - metabolism</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 3</subject><subject>Endothelial Cells - cytology</subject><subject>Heart Rate</subject><subject>Hematocrit</subject><subject>ischemia-reperfusion injury</subject><subject>ischemic pre-conditioning</subject><subject>Ischemic Preconditioning - methods</subject><subject>Leukocytes - cytology</subject><subject>Liver - blood supply</subject><subject>Liver - cytology</subject><subject>Liver - metabolism</subject><subject>Liver Circulation - drug effects</subject><subject>Liver Transplantation</subject><subject>Male</subject><subject>microcirculation</subject><subject>Microcirculation - drug effects</subject><subject>Microscopy, Video</subject><subject>Milrinone - pharmacology</subject><subject>Nitric Oxide - metabolism</subject><subject>phosphodiesterase inhibitor</subject><subject>Phosphodiesterase Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reperfusion Injury - drug therapy</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Venules - drug effects</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLFu2zAQhomiQeI4eYAuhaZOlXIUKVJGp8JtEwMu4iGZCYo6VTQk0iXlAB775qFrA9nC5XDgfx_uPkI-USgoUHG3LbYxFiWAKKAqgNUfyIzCosprIdlHMgMoy5zXwK_IdYxbSP1CsktyRSXwSlA2I_9-HJwercmWvXZ_MGa-yzY-Tvkqmh6PHw-401Oqv60J3thg9kPqvctW4y74F2yz5pDpbBMwfwqopxHd9J_S-7jrfWsxThh0xJxlK9fbxk4-fE24IVjnHd6Qi04PEW_PdU6ef_18Wj7k68f71fL7OjecyikvNetM2ZgGJNPpdWXTCsrFoqJalkY2ElglBLQSeU3LFMCaQ1MLkJzRumNz8uXETVv_3ael1GijwWHQDv0-KlFTwXjyMyf0FEz3xhiwU7tgRx0OioI6eldblbyro3cFlUre08znM3zfjNi-TZxFp8C3UwDTiS8Wg4rGojPY2oBmUq237-BfAUqplOA</recordid><startdate>20061201</startdate><enddate>20061201</enddate><creator>Kume, Makoto</creator><creator>Banafsche, Ramin</creator><creator>Yamamoto, Yuzo</creator><creator>Yamaoka, Yoshio</creator><creator>Nobiling, Rainer</creator><creator>Gebhard, Martha-Maria</creator><creator>Klar, Ernst</creator><general>Elsevier Inc</general><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>20061201</creationdate><title>Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone</title><author>Kume, Makoto ; Banafsche, Ramin ; Yamamoto, Yuzo ; Yamaoka, Yoshio ; Nobiling, Rainer ; Gebhard, Martha-Maria ; Klar, Ernst</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-2a3fc2bcb073aaaaf2bd6146951a72c7b7035660d7e4812aafe840b86074318f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors</topic><topic>Animals</topic><topic>Blood Pressure</topic><topic>Cell Communication - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>cyclic AMP</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic GMP - metabolism</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 3</topic><topic>Endothelial Cells - cytology</topic><topic>Heart Rate</topic><topic>Hematocrit</topic><topic>ischemia-reperfusion injury</topic><topic>ischemic pre-conditioning</topic><topic>Ischemic Preconditioning - methods</topic><topic>Leukocytes - cytology</topic><topic>Liver - blood supply</topic><topic>Liver - cytology</topic><topic>Liver - metabolism</topic><topic>Liver Circulation - drug effects</topic><topic>Liver Transplantation</topic><topic>Male</topic><topic>microcirculation</topic><topic>Microcirculation - drug effects</topic><topic>Microscopy, Video</topic><topic>Milrinone - pharmacology</topic><topic>Nitric Oxide - metabolism</topic><topic>phosphodiesterase inhibitor</topic><topic>Phosphodiesterase Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reperfusion Injury - drug therapy</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Venules - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kume, Makoto</creatorcontrib><creatorcontrib>Banafsche, Ramin</creatorcontrib><creatorcontrib>Yamamoto, Yuzo</creatorcontrib><creatorcontrib>Yamaoka, Yoshio</creatorcontrib><creatorcontrib>Nobiling, Rainer</creatorcontrib><creatorcontrib>Gebhard, Martha-Maria</creatorcontrib><creatorcontrib>Klar, Ernst</creatorcontrib><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>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kume, Makoto</au><au>Banafsche, Ramin</au><au>Yamamoto, Yuzo</au><au>Yamaoka, Yoshio</au><au>Nobiling, Rainer</au><au>Gebhard, Martha-Maria</au><au>Klar, Ernst</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2006-12-01</date><risdate>2006</risdate><volume>136</volume><issue>2</issue><spage>209</spage><epage>218</epage><pages>209-218</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy.
Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively.
In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls.
The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17045613</pmid><doi>10.1016/j.jss.2006.05.038</doi><tpages>10</tpages></addata></record> |
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| subjects | 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors Animals Blood Pressure Cell Communication - drug effects Cell Survival - drug effects cyclic AMP Cyclic AMP - metabolism Cyclic GMP - metabolism Cyclic Nucleotide Phosphodiesterases, Type 3 Endothelial Cells - cytology Heart Rate Hematocrit ischemia-reperfusion injury ischemic pre-conditioning Ischemic Preconditioning - methods Leukocytes - cytology Liver - blood supply Liver - cytology Liver - metabolism Liver Circulation - drug effects Liver Transplantation Male microcirculation Microcirculation - drug effects Microscopy, Video Milrinone - pharmacology Nitric Oxide - metabolism phosphodiesterase inhibitor Phosphodiesterase Inhibitors - pharmacology Rats Rats, Wistar Reperfusion Injury - drug therapy Reperfusion Injury - prevention & control Venules - drug effects |
| title | Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone |
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