Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model
Carvedilol, a selective α 1 and non-selective β-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol...
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| Veröffentlicht in: | European journal of pharmacology 1998-06, Vol.351 (3), p.341-350 |
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| creator | Feuerstein, Giora Liu, Gao-Lin Yue, Tian-Li Cheng, H-Y Hieble, J.Paul Arch, Jonathan R.S Ruffolo, Robert R Ma, X.-L |
| description | Carvedilol, a selective
α
1 and non-selective
β-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a
β
1-selective adrenoceptor antagonist, metoprolol. Carvedilol (1 mg/kg) or metoprolol (1 mg/kg or 1 mg/kg+0.5 mg/kg 90 min later) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (60 min) and reperfusion (180 min) resulted in significant increments in left ventricular end diastolic pressure, large infarcts (59±2.6% of area-at-risk) and marked increase in myeloperoxidase activity (0.59±0.09 U/100 mg tissue). Carvedilol treatment resulted in sustained reduction of pressure-rate-index and significantly smaller infarcts (22.0±2.5%,
P |
| doi_str_mv | 10.1016/S0014-2999(98)00326-4 |
| format | Article |
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α
1 and non-selective
β-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a
β
1-selective adrenoceptor antagonist, metoprolol. Carvedilol (1 mg/kg) or metoprolol (1 mg/kg or 1 mg/kg+0.5 mg/kg 90 min later) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (60 min) and reperfusion (180 min) resulted in significant increments in left ventricular end diastolic pressure, large infarcts (59±2.6% of area-at-risk) and marked increase in myeloperoxidase activity (0.59±0.09 U/100 mg tissue). Carvedilol treatment resulted in sustained reduction of pressure-rate-index and significantly smaller infarcts (22.0±2.5%,
P<0.01 vs. vehicle) as well as decreased myeloperoxidase activity (0.186±0.056 U/100 mg tissue,
P<0.01 vs. vehicle). The highest dose of metoprolol, 1 mg/kg+0.5 mg/kg, that resulted in pressure-rate-index comparable to that of 1.0 mg/kg carvedilol, failed to reduce myeloperoxidase activity in the ischemic myocardial tissue, and the infarct size (35±3.1%) was significantly larger than in carvedilol-treated animals. Taken together, this study suggests that the superior cardioprotection of carvedilol over metoprolol is not a consequence of hemodynamic variances but possibly the result of the additional pharmacological properties of carvedilol such as the antioxidant and anti-neutrophil effects.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/S0014-2999(98)00326-4</identifier><identifier>PMID: 9721026</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Adrenergic alpha-Antagonists - chemistry ; Adrenergic alpha-Antagonists - metabolism ; Adrenergic alpha-Antagonists - pharmacology ; Adrenergic beta-Antagonists - chemistry ; Adrenergic beta-Antagonists - metabolism ; Adrenergic beta-Antagonists - pharmacology ; Animals ; Antianginal agents. Coronary vasodilator agents ; Antioxidants - chemistry ; Antioxidants - metabolism ; Antioxidants - pharmacology ; Biological and medical sciences ; Blood Pressure - drug effects ; Carbazoles - chemistry ; Carbazoles - metabolism ; Carbazoles - pharmacology ; Cardiovascular system ; Carvedilol ; Heart Rate - drug effects ; Leukocyte ; Male ; Medical sciences ; Metoprolol ; Metoprolol - chemistry ; Metoprolol - metabolism ; Metoprolol - pharmacology ; Myocardial infarction ; Myocardial Infarction - etiology ; Myocardial Infarction - pathology ; Myocardial Infarction - prevention & control ; Myocardial Ischemia - complications ; Myocardial Ischemia - pathology ; Myocardial Ischemia - physiopathology ; Myocardial Ischemia - prevention & control ; Myocardial Reperfusion Injury - complications ; Myocardial Reperfusion Injury - pathology ; Myocardial Reperfusion Injury - physiopathology ; Myocardial Reperfusion Injury - prevention & control ; Myocardium - enzymology ; Myocardium - pathology ; Oxidation-Reduction ; Peroxidase - metabolism ; Pharmacology. Drug treatments ; Propanolamines - chemistry ; Propanolamines - metabolism ; Propanolamines - pharmacology ; Propranolol - chemistry ; Propranolol - metabolism ; Propranolol - pharmacology ; Rabbits ; Receptors, Adrenergic, beta-1 - metabolism ; Receptors, Adrenergic, beta-2 - metabolism ; Recombinant Proteins - metabolism ; Solubility ; Ventricular Function, Left - drug effects ; Ventricular Pressure - drug effects ; β-adrenoceptor antagonist</subject><ispartof>European journal of pharmacology, 1998-06, Vol.351 (3), p.341-350</ispartof><rights>1998 Elsevier Science B.V.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-1ecfed97fac124fa75eb9e804532d621299898dba07ef6d467c15d31ac66e6753</citedby><cites>FETCH-LOGICAL-c455t-1ecfed97fac124fa75eb9e804532d621299898dba07ef6d467c15d31ac66e6753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0014-2999(98)00326-4$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2386518$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9721026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feuerstein, Giora</creatorcontrib><creatorcontrib>Liu, Gao-Lin</creatorcontrib><creatorcontrib>Yue, Tian-Li</creatorcontrib><creatorcontrib>Cheng, H-Y</creatorcontrib><creatorcontrib>Hieble, J.Paul</creatorcontrib><creatorcontrib>Arch, Jonathan R.S</creatorcontrib><creatorcontrib>Ruffolo, Robert R</creatorcontrib><creatorcontrib>Ma, X.-L</creatorcontrib><title>Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Carvedilol, a selective
α
1 and non-selective
β-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a
β
1-selective adrenoceptor antagonist, metoprolol. Carvedilol (1 mg/kg) or metoprolol (1 mg/kg or 1 mg/kg+0.5 mg/kg 90 min later) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (60 min) and reperfusion (180 min) resulted in significant increments in left ventricular end diastolic pressure, large infarcts (59±2.6% of area-at-risk) and marked increase in myeloperoxidase activity (0.59±0.09 U/100 mg tissue). Carvedilol treatment resulted in sustained reduction of pressure-rate-index and significantly smaller infarcts (22.0±2.5%,
P<0.01 vs. vehicle) as well as decreased myeloperoxidase activity (0.186±0.056 U/100 mg tissue,
P<0.01 vs. vehicle). The highest dose of metoprolol, 1 mg/kg+0.5 mg/kg, that resulted in pressure-rate-index comparable to that of 1.0 mg/kg carvedilol, failed to reduce myeloperoxidase activity in the ischemic myocardial tissue, and the infarct size (35±3.1%) was significantly larger than in carvedilol-treated animals. Taken together, this study suggests that the superior cardioprotection of carvedilol over metoprolol is not a consequence of hemodynamic variances but possibly the result of the additional pharmacological properties of carvedilol such as the antioxidant and anti-neutrophil effects.</description><subject>Adrenergic alpha-Antagonists - chemistry</subject><subject>Adrenergic alpha-Antagonists - metabolism</subject><subject>Adrenergic alpha-Antagonists - pharmacology</subject><subject>Adrenergic beta-Antagonists - chemistry</subject><subject>Adrenergic beta-Antagonists - metabolism</subject><subject>Adrenergic beta-Antagonists - pharmacology</subject><subject>Animals</subject><subject>Antianginal agents. Coronary vasodilator agents</subject><subject>Antioxidants - chemistry</subject><subject>Antioxidants - metabolism</subject><subject>Antioxidants - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Carbazoles - chemistry</subject><subject>Carbazoles - metabolism</subject><subject>Carbazoles - pharmacology</subject><subject>Cardiovascular system</subject><subject>Carvedilol</subject><subject>Heart Rate - drug effects</subject><subject>Leukocyte</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metoprolol</subject><subject>Metoprolol - chemistry</subject><subject>Metoprolol - metabolism</subject><subject>Metoprolol - pharmacology</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - etiology</subject><subject>Myocardial Infarction - pathology</subject><subject>Myocardial Infarction - prevention & control</subject><subject>Myocardial Ischemia - complications</subject><subject>Myocardial Ischemia - pathology</subject><subject>Myocardial Ischemia - physiopathology</subject><subject>Myocardial Ischemia - prevention & control</subject><subject>Myocardial Reperfusion Injury - complications</subject><subject>Myocardial Reperfusion Injury - pathology</subject><subject>Myocardial Reperfusion Injury - physiopathology</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Myocardium - enzymology</subject><subject>Myocardium - pathology</subject><subject>Oxidation-Reduction</subject><subject>Peroxidase - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Propanolamines - chemistry</subject><subject>Propanolamines - metabolism</subject><subject>Propanolamines - pharmacology</subject><subject>Propranolol - chemistry</subject><subject>Propranolol - metabolism</subject><subject>Propranolol - pharmacology</subject><subject>Rabbits</subject><subject>Receptors, Adrenergic, beta-1 - metabolism</subject><subject>Receptors, Adrenergic, beta-2 - metabolism</subject><subject>Recombinant Proteins - metabolism</subject><subject>Solubility</subject><subject>Ventricular Function, Left - drug effects</subject><subject>Ventricular Pressure - drug effects</subject><subject>β-adrenoceptor antagonist</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu1DAURa2KqgyFT6iUBUKwCNhObMcrhEZAkSp1Qbu2Xuzn1iiJg52p1L_HmRlm25Vl3fP8rg8hV4x-ZpTJL78pZW3NtdYfdfeJ0obLuj0jG9YpXVPF-CuyOSGvyZuc_1BKhebiglxoxRnlckPSNo4zpJDjVEVfjbjEOcUhDhVMrrKQntCF9To_QhrBlujh-X_mwgovaJdQxsNUJej7sFQh20ccA-y5hDMmv8srMkaHw1ty7mHI-O54XpL7H9_vttf1ze3PX9tvN7VthVhqhtaj08qDZbz1oAT2GjvaioY7yVn5Vqc71wNV6KVrpbJMuIaBlRKlEs0l-XB4t3T8u8O8mLEUw2GACeMuG9V0kiulCigOoE0x54TezCmMkJ4No2Z1bfauzSrS6M7sXZu2zF0dF-z6Ed1p6ii35O-POWQLg08w2ZBPGC_7BesK9vWAYZHxFDCZbANOtohPRa1xMbxQ5B-c-J3A</recordid><startdate>19980626</startdate><enddate>19980626</enddate><creator>Feuerstein, Giora</creator><creator>Liu, Gao-Lin</creator><creator>Yue, Tian-Li</creator><creator>Cheng, H-Y</creator><creator>Hieble, J.Paul</creator><creator>Arch, Jonathan R.S</creator><creator>Ruffolo, Robert R</creator><creator>Ma, X.-L</creator><general>Elsevier B.V</general><general>Elsevier</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>19980626</creationdate><title>Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model</title><author>Feuerstein, Giora ; Liu, Gao-Lin ; Yue, Tian-Li ; Cheng, H-Y ; Hieble, J.Paul ; Arch, Jonathan R.S ; Ruffolo, Robert R ; Ma, X.-L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-1ecfed97fac124fa75eb9e804532d621299898dba07ef6d467c15d31ac66e6753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adrenergic alpha-Antagonists - chemistry</topic><topic>Adrenergic alpha-Antagonists - metabolism</topic><topic>Adrenergic alpha-Antagonists - pharmacology</topic><topic>Adrenergic beta-Antagonists - chemistry</topic><topic>Adrenergic beta-Antagonists - metabolism</topic><topic>Adrenergic beta-Antagonists - pharmacology</topic><topic>Animals</topic><topic>Antianginal agents. Coronary vasodilator agents</topic><topic>Antioxidants - chemistry</topic><topic>Antioxidants - metabolism</topic><topic>Antioxidants - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Carbazoles - chemistry</topic><topic>Carbazoles - metabolism</topic><topic>Carbazoles - pharmacology</topic><topic>Cardiovascular system</topic><topic>Carvedilol</topic><topic>Heart Rate - drug effects</topic><topic>Leukocyte</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metoprolol</topic><topic>Metoprolol - chemistry</topic><topic>Metoprolol - metabolism</topic><topic>Metoprolol - pharmacology</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - etiology</topic><topic>Myocardial Infarction - pathology</topic><topic>Myocardial Infarction - prevention & control</topic><topic>Myocardial Ischemia - complications</topic><topic>Myocardial Ischemia - pathology</topic><topic>Myocardial Ischemia - physiopathology</topic><topic>Myocardial Ischemia - prevention & control</topic><topic>Myocardial Reperfusion Injury - complications</topic><topic>Myocardial Reperfusion Injury - pathology</topic><topic>Myocardial Reperfusion Injury - physiopathology</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - pathology</topic><topic>Oxidation-Reduction</topic><topic>Peroxidase - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Propanolamines - chemistry</topic><topic>Propanolamines - metabolism</topic><topic>Propanolamines - pharmacology</topic><topic>Propranolol - chemistry</topic><topic>Propranolol - metabolism</topic><topic>Propranolol - pharmacology</topic><topic>Rabbits</topic><topic>Receptors, Adrenergic, beta-1 - metabolism</topic><topic>Receptors, Adrenergic, beta-2 - metabolism</topic><topic>Recombinant Proteins - metabolism</topic><topic>Solubility</topic><topic>Ventricular Function, Left - drug effects</topic><topic>Ventricular Pressure - drug effects</topic><topic>β-adrenoceptor antagonist</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feuerstein, Giora</creatorcontrib><creatorcontrib>Liu, Gao-Lin</creatorcontrib><creatorcontrib>Yue, Tian-Li</creatorcontrib><creatorcontrib>Cheng, H-Y</creatorcontrib><creatorcontrib>Hieble, J.Paul</creatorcontrib><creatorcontrib>Arch, Jonathan R.S</creatorcontrib><creatorcontrib>Ruffolo, Robert R</creatorcontrib><creatorcontrib>Ma, X.-L</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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feuerstein, Giora</au><au>Liu, Gao-Lin</au><au>Yue, Tian-Li</au><au>Cheng, H-Y</au><au>Hieble, J.Paul</au><au>Arch, Jonathan R.S</au><au>Ruffolo, Robert R</au><au>Ma, X.-L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1998-06-26</date><risdate>1998</risdate><volume>351</volume><issue>3</issue><spage>341</spage><epage>350</epage><pages>341-350</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Carvedilol, a selective
α
1 and non-selective
β-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a
β
1-selective adrenoceptor antagonist, metoprolol. Carvedilol (1 mg/kg) or metoprolol (1 mg/kg or 1 mg/kg+0.5 mg/kg 90 min later) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (60 min) and reperfusion (180 min) resulted in significant increments in left ventricular end diastolic pressure, large infarcts (59±2.6% of area-at-risk) and marked increase in myeloperoxidase activity (0.59±0.09 U/100 mg tissue). Carvedilol treatment resulted in sustained reduction of pressure-rate-index and significantly smaller infarcts (22.0±2.5%,
P<0.01 vs. vehicle) as well as decreased myeloperoxidase activity (0.186±0.056 U/100 mg tissue,
P<0.01 vs. vehicle). The highest dose of metoprolol, 1 mg/kg+0.5 mg/kg, that resulted in pressure-rate-index comparable to that of 1.0 mg/kg carvedilol, failed to reduce myeloperoxidase activity in the ischemic myocardial tissue, and the infarct size (35±3.1%) was significantly larger than in carvedilol-treated animals. Taken together, this study suggests that the superior cardioprotection of carvedilol over metoprolol is not a consequence of hemodynamic variances but possibly the result of the additional pharmacological properties of carvedilol such as the antioxidant and anti-neutrophil effects.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>9721026</pmid><doi>10.1016/S0014-2999(98)00326-4</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-2999 |
| ispartof | European journal of pharmacology, 1998-06, Vol.351 (3), p.341-350 |
| issn | 0014-2999 1879-0712 |
| language | eng |
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| subjects | Adrenergic alpha-Antagonists - chemistry Adrenergic alpha-Antagonists - metabolism Adrenergic alpha-Antagonists - pharmacology Adrenergic beta-Antagonists - chemistry Adrenergic beta-Antagonists - metabolism Adrenergic beta-Antagonists - pharmacology Animals Antianginal agents. Coronary vasodilator agents Antioxidants - chemistry Antioxidants - metabolism Antioxidants - pharmacology Biological and medical sciences Blood Pressure - drug effects Carbazoles - chemistry Carbazoles - metabolism Carbazoles - pharmacology Cardiovascular system Carvedilol Heart Rate - drug effects Leukocyte Male Medical sciences Metoprolol Metoprolol - chemistry Metoprolol - metabolism Metoprolol - pharmacology Myocardial infarction Myocardial Infarction - etiology Myocardial Infarction - pathology Myocardial Infarction - prevention & control Myocardial Ischemia - complications Myocardial Ischemia - pathology Myocardial Ischemia - physiopathology Myocardial Ischemia - prevention & control Myocardial Reperfusion Injury - complications Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - physiopathology Myocardial Reperfusion Injury - prevention & control Myocardium - enzymology Myocardium - pathology Oxidation-Reduction Peroxidase - metabolism Pharmacology. Drug treatments Propanolamines - chemistry Propanolamines - metabolism Propanolamines - pharmacology Propranolol - chemistry Propranolol - metabolism Propranolol - pharmacology Rabbits Receptors, Adrenergic, beta-1 - metabolism Receptors, Adrenergic, beta-2 - metabolism Recombinant Proteins - metabolism Solubility Ventricular Function, Left - drug effects Ventricular Pressure - drug effects β-adrenoceptor antagonist |
| title | Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model |
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