Adriamycin cardiomyopathy: Implications of cellular changes in a canine model with mild impairment of left ventricular function
The present study has examined early cellular effects of chronic adriamycin administration to dogs using a protocol (1 mg/kg/week to a total cumulative dose of 240 mg/m 2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to t...
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| Veröffentlicht in: | Biochemical pharmacology 1985-11, Vol.34 (22), p.4033-4041 |
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| container_title | Biochemical pharmacology |
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| creator | Tomlinson, Charles W. Godin, David V. Rabkin, Simon W. |
| description | The present study has examined early cellular effects of chronic adriamycin administration to dogs using a protocol (1 mg/kg/week to a total cumulative dose of 240 mg/m
2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to the development of clinical or radiological manifestations of heart failure. At this early phase of cardiomyopathy, significant reduction (
P < 0.05) in sarcoplasmic reticulum Ca
2+, K
+-ATPase was observed without any change in mitochondrial, lysosomal or sarcolemmal marker enzymes. Myocardial calcium (
P < 0.01) and glutathione (
P < 0.001) levels were increased significantly. Detailed analysis of myocardial phospholipid profiles failed to show any significant differences between control and treated dogs. In contrast, red cell membranes showed increased phosphatidylcholine (PC) and decreased phosphatidylserine (PS) contents, resulting in a significant increase in PC/PS ratio (
P < 0.05). No significant changes were detected in activities of catalase, superoxide dismutase or glutathione peroxidase in erythrocytes or myocardial tissue from control and adriamycin-treated animals. A significant (
P < 0.05) elevation in plasma sialic acid was observed following adriamycin treatment. Our results suggest that early adriamycin-induced damage is unlikely to result from alterations in cellular processes protecting tissues against oxidant injury. Regression analysis indicated that, of the various abnormalities observed, only the elevated myocardial calcium levels and the increases in plasma sialic acid correlated with the degree of myocardial functional impairment. Our findings suggest the presence of sarcolemmal alterations in Ca
2+ handling in early adriamycin-induced myocardial injury and indicate that measurement of plasma sialic acid should be further investigated as a possible noninvasive indicator of impending adriamycin cardiotoxicity. |
| doi_str_mv | 10.1016/0006-2952(85)90384-3 |
| format | Article |
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2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to the development of clinical or radiological manifestations of heart failure. At this early phase of cardiomyopathy, significant reduction (
P < 0.05) in sarcoplasmic reticulum Ca
2+, K
+-ATPase was observed without any change in mitochondrial, lysosomal or sarcolemmal marker enzymes. Myocardial calcium (
P < 0.01) and glutathione (
P < 0.001) levels were increased significantly. Detailed analysis of myocardial phospholipid profiles failed to show any significant differences between control and treated dogs. In contrast, red cell membranes showed increased phosphatidylcholine (PC) and decreased phosphatidylserine (PS) contents, resulting in a significant increase in PC/PS ratio (
P < 0.05). No significant changes were detected in activities of catalase, superoxide dismutase or glutathione peroxidase in erythrocytes or myocardial tissue from control and adriamycin-treated animals. A significant (
P < 0.05) elevation in plasma sialic acid was observed following adriamycin treatment. Our results suggest that early adriamycin-induced damage is unlikely to result from alterations in cellular processes protecting tissues against oxidant injury. Regression analysis indicated that, of the various abnormalities observed, only the elevated myocardial calcium levels and the increases in plasma sialic acid correlated with the degree of myocardial functional impairment. Our findings suggest the presence of sarcolemmal alterations in Ca
2+ handling in early adriamycin-induced myocardial injury and indicate that measurement of plasma sialic acid should be further investigated as a possible noninvasive indicator of impending adriamycin cardiotoxicity.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/0006-2952(85)90384-3</identifier><identifier>PMID: 2998397</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Calcium-Transporting ATPases - analysis ; Cardiomyopathies - chemically induced ; Cardiomyopathies - pathology ; Cardiomyopathies - physiopathology ; Disease Models, Animal ; Dogs ; Doxorubicin - toxicity ; Drug toxicity and drugs side effects treatment ; Echocardiography ; Electron Transport Complex IV - antagonists & inhibitors ; Free Radicals ; Glutathione - analysis ; Heart - physiopathology ; Medical sciences ; Myocardium - analysis ; Pharmacology. Drug treatments ; Phospholipids - analysis ; Toxicity: cardiovascular system</subject><ispartof>Biochemical pharmacology, 1985-11, Vol.34 (22), p.4033-4041</ispartof><rights>1985</rights><rights>1986 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-bf20a8cfc7251bd8965a1f3c577d490e6ef0de6f87762dad918cfde05a5128313</citedby><cites>FETCH-LOGICAL-c417t-bf20a8cfc7251bd8965a1f3c577d490e6ef0de6f87762dad918cfde05a5128313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0006295285903843$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8716276$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2998397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomlinson, Charles W.</creatorcontrib><creatorcontrib>Godin, David V.</creatorcontrib><creatorcontrib>Rabkin, Simon W.</creatorcontrib><title>Adriamycin cardiomyopathy: Implications of cellular changes in a canine model with mild impairment of left ventricular function</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>The present study has examined early cellular effects of chronic adriamycin administration to dogs using a protocol (1 mg/kg/week to a total cumulative dose of 240 mg/m
2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to the development of clinical or radiological manifestations of heart failure. At this early phase of cardiomyopathy, significant reduction (
P < 0.05) in sarcoplasmic reticulum Ca
2+, K
+-ATPase was observed without any change in mitochondrial, lysosomal or sarcolemmal marker enzymes. Myocardial calcium (
P < 0.01) and glutathione (
P < 0.001) levels were increased significantly. Detailed analysis of myocardial phospholipid profiles failed to show any significant differences between control and treated dogs. In contrast, red cell membranes showed increased phosphatidylcholine (PC) and decreased phosphatidylserine (PS) contents, resulting in a significant increase in PC/PS ratio (
P < 0.05). No significant changes were detected in activities of catalase, superoxide dismutase or glutathione peroxidase in erythrocytes or myocardial tissue from control and adriamycin-treated animals. A significant (
P < 0.05) elevation in plasma sialic acid was observed following adriamycin treatment. Our results suggest that early adriamycin-induced damage is unlikely to result from alterations in cellular processes protecting tissues against oxidant injury. Regression analysis indicated that, of the various abnormalities observed, only the elevated myocardial calcium levels and the increases in plasma sialic acid correlated with the degree of myocardial functional impairment. Our findings suggest the presence of sarcolemmal alterations in Ca
2+ handling in early adriamycin-induced myocardial injury and indicate that measurement of plasma sialic acid should be further investigated as a possible noninvasive indicator of impending adriamycin cardiotoxicity.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium-Transporting ATPases - analysis</subject><subject>Cardiomyopathies - chemically induced</subject><subject>Cardiomyopathies - pathology</subject><subject>Cardiomyopathies - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Dogs</subject><subject>Doxorubicin - toxicity</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Echocardiography</subject><subject>Electron Transport Complex IV - antagonists & inhibitors</subject><subject>Free Radicals</subject><subject>Glutathione - analysis</subject><subject>Heart - physiopathology</subject><subject>Medical sciences</subject><subject>Myocardium - analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Phospholipids - analysis</subject><subject>Toxicity: cardiovascular system</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1vFSEUhomxqdfqP9CEhTG6mArzAUwXJk2jtkmTbnRNuHDwYvgYYabmrvzrMr03d-mKHM7zvoEHoTeUXFJC2SdCCGvacWg_iOHjSDrRN90ztKGCd_Waiedoc0JeoJel_FpHweg5Om_HUXQj36C_1yY7FfbaRaxVNi6FfZrUvNtf4bsweafV7FIsOFmswfvFq4z1TsWfUHDNqJqKLgIOyYDHf9y8w8F5g12YlMsB4rxGPdgZP9YhO_1UYZeo1-JX6MwqX-D18bxAP75--X5z29w_fLu7ub5vdE_53GxtS5TQVvN2oFsjRjYoajs9cG76kQADSwwwKzhnrVFmpBU2QAY10FZ0tLtA7w-9U06_FyizDK6sH1IR0lIk7RknnHcV7A-gzqmUDFZO2QWV95ISuXqXq0W5SpVikE_e5Rp7e-xftgHMKXQUXffvjntVtPI2q6hdOWGCU9ZyVrHPBwyqi0cHWRbtIGowLoOepUnu_-_4B4ZgoVw</recordid><startdate>19851115</startdate><enddate>19851115</enddate><creator>Tomlinson, Charles W.</creator><creator>Godin, David V.</creator><creator>Rabkin, Simon W.</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7U7</scope><scope>C1K</scope></search><sort><creationdate>19851115</creationdate><title>Adriamycin cardiomyopathy: Implications of cellular changes in a canine model with mild impairment of left ventricular function</title><author>Tomlinson, Charles W. ; Godin, David V. ; Rabkin, Simon W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-bf20a8cfc7251bd8965a1f3c577d490e6ef0de6f87762dad918cfde05a5128313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium-Transporting ATPases - analysis</topic><topic>Cardiomyopathies - chemically induced</topic><topic>Cardiomyopathies - pathology</topic><topic>Cardiomyopathies - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Dogs</topic><topic>Doxorubicin - toxicity</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Echocardiography</topic><topic>Electron Transport Complex IV - antagonists & inhibitors</topic><topic>Free Radicals</topic><topic>Glutathione - analysis</topic><topic>Heart - physiopathology</topic><topic>Medical sciences</topic><topic>Myocardium - analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Phospholipids - analysis</topic><topic>Toxicity: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tomlinson, Charles W.</creatorcontrib><creatorcontrib>Godin, David V.</creatorcontrib><creatorcontrib>Rabkin, Simon W.</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tomlinson, Charles W.</au><au>Godin, David V.</au><au>Rabkin, Simon W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adriamycin cardiomyopathy: Implications of cellular changes in a canine model with mild impairment of left ventricular function</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1985-11-15</date><risdate>1985</risdate><volume>34</volume><issue>22</issue><spage>4033</spage><epage>4041</epage><pages>4033-4041</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>The present study has examined early cellular effects of chronic adriamycin administration to dogs using a protocol (1 mg/kg/week to a total cumulative dose of 240 mg/m
2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to the development of clinical or radiological manifestations of heart failure. At this early phase of cardiomyopathy, significant reduction (
P < 0.05) in sarcoplasmic reticulum Ca
2+, K
+-ATPase was observed without any change in mitochondrial, lysosomal or sarcolemmal marker enzymes. Myocardial calcium (
P < 0.01) and glutathione (
P < 0.001) levels were increased significantly. Detailed analysis of myocardial phospholipid profiles failed to show any significant differences between control and treated dogs. In contrast, red cell membranes showed increased phosphatidylcholine (PC) and decreased phosphatidylserine (PS) contents, resulting in a significant increase in PC/PS ratio (
P < 0.05). No significant changes were detected in activities of catalase, superoxide dismutase or glutathione peroxidase in erythrocytes or myocardial tissue from control and adriamycin-treated animals. A significant (
P < 0.05) elevation in plasma sialic acid was observed following adriamycin treatment. Our results suggest that early adriamycin-induced damage is unlikely to result from alterations in cellular processes protecting tissues against oxidant injury. Regression analysis indicated that, of the various abnormalities observed, only the elevated myocardial calcium levels and the increases in plasma sialic acid correlated with the degree of myocardial functional impairment. Our findings suggest the presence of sarcolemmal alterations in Ca
2+ handling in early adriamycin-induced myocardial injury and indicate that measurement of plasma sialic acid should be further investigated as a possible noninvasive indicator of impending adriamycin cardiotoxicity.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>2998397</pmid><doi>10.1016/0006-2952(85)90384-3</doi><tpages>9</tpages></addata></record> |
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| ispartof | Biochemical pharmacology, 1985-11, Vol.34 (22), p.4033-4041 |
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| subjects | Animals Biological and medical sciences Calcium-Transporting ATPases - analysis Cardiomyopathies - chemically induced Cardiomyopathies - pathology Cardiomyopathies - physiopathology Disease Models, Animal Dogs Doxorubicin - toxicity Drug toxicity and drugs side effects treatment Echocardiography Electron Transport Complex IV - antagonists & inhibitors Free Radicals Glutathione - analysis Heart - physiopathology Medical sciences Myocardium - analysis Pharmacology. Drug treatments Phospholipids - analysis Toxicity: cardiovascular system |
| title | Adriamycin cardiomyopathy: Implications of cellular changes in a canine model with mild impairment of left ventricular function |
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