Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction
Mesenchymal stem cells （MSCs） have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction （AMI）. However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefor...
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| Veröffentlicht in: | Acta biochimica et biophysica Sinica 2011-11, Vol.43 (11), p.857-866 |
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| creator | Cai, Anping Zheng, Dongdan Dong, Yugang Qiu, Ruofeng Huang, Yuli Song, Yuanbin Jiang, Zhigao Rao, Shaoqi Liao, Xinxue Kuang, Jian Dai, Gang Mai, Weiyi |
| description | Mesenchymal stem cells （MSCs） have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction （AMI）. However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells （ASCs）, and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 （a transcription factor） and cardiac troponin-I were detected by cellular immuno-fluorescence. Atorvastatin （Ator group） or vehicle （control group） was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 x 106 co-ASCs/100 μl phosphate-buffered saline （PBS）, 1×10^6 ASCs/100 μl PBS, or 100 μl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-I was 22.8%±3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines （VCAM-1, TNF-α, Hs-CRP） mRNA expression, and Bax protein expression were sig- nificantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function （P〈0.05）. Compared with the Ator2 ＋ ASCs group and Con ＋ co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 ＋ co-ASCs group （P〈 0.05）. Pre-amelio-ration of the cardiac milieu, in conjunction with prespecification of ASCs, was beneficial for enhancing ASCs＇ therapeutic efficacy on cardiac function after AMI. |
| doi_str_mv | 10.1093/abbs/gmr087 |
| format | Article |
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However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells （ASCs）, and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 （a transcription factor） and cardiac troponin-I were detected by cellular immuno-fluorescence. Atorvastatin （Ator group） or vehicle （control group） was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 x 106 co-ASCs/100 μl phosphate-buffered saline （PBS）, 1×10^6 ASCs/100 μl PBS, or 100 μl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-I was 22.8%±3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines （VCAM-1, TNF-α, Hs-CRP） mRNA expression, and Bax protein expression were sig- nificantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function （P〈0.05）. Compared with the Ator2 ＋ ASCs group and Con ＋ co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 ＋ co-ASCs group （P〈 0.05）. Pre-amelio-ration of the cardiac milieu, in conjunction with prespecification of ASCs, was beneficial for enhancing ASCs＇ therapeutic efficacy on cardiac function after AMI.</description><identifier>ISSN: 1672-9145</identifier><identifier>EISSN: 1745-7270</identifier><identifier>DOI: 10.1093/abbs/gmr087</identifier><identifier>PMID: 21983658</identifier><language>eng</language><publisher>China: Oxford University Press</publisher><subject>Adipose Tissue - cytology ; Adipose Tissue - transplantation ; Animals ; Atorvastatin Calcium ; bcl-2-Associated X Protein - drug effects ; bcl-2-Associated X Protein - metabolism ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; Cells, Cultured ; Coculture Techniques ; Disease Models, Animal ; GATA4 Transcription Factor - metabolism ; Heart Function Tests ; Heptanoic Acids - pharmacology ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells - metabolism ; Myocardial Infarction - metabolism ; Myocardial Infarction - therapy ; Myocytes, Cardiac - metabolism ; Proto-Oncogene Proteins c-bcl-2 - drug effects ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Pyrroles - pharmacology ; Rats ; Rats, Sprague-Dawley ; Troponin I - metabolism ; Tumor Necrosis Factor-alpha - drug effects ; Tumor Necrosis Factor-alpha - metabolism ; Vascular Cell Adhesion Molecule-1 - drug effects ; Vascular Cell Adhesion Molecule-1 - metabolism ; 大鼠 ; 心肌肌钙蛋白I ; 心脏功能 ; 急性心肌梗死 ; 疗效 ; 细胞移植 ; 脂肪来源 ; 间充质干细胞</subject><ispartof>Acta biochimica et biophysica Sinica, 2011-11, Vol.43 (11), p.857-866</ispartof><rights>The Author 2011. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-d47115175f0c2c9e2aa4fe99ea903023445b2430793afa3fd699e0716c5380923</citedby><cites>FETCH-LOGICAL-c415t-d47115175f0c2c9e2aa4fe99ea903023445b2430793afa3fd699e0716c5380923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/90160X/90160X.jpg</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21983658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Anping</creatorcontrib><creatorcontrib>Zheng, Dongdan</creatorcontrib><creatorcontrib>Dong, Yugang</creatorcontrib><creatorcontrib>Qiu, Ruofeng</creatorcontrib><creatorcontrib>Huang, Yuli</creatorcontrib><creatorcontrib>Song, Yuanbin</creatorcontrib><creatorcontrib>Jiang, Zhigao</creatorcontrib><creatorcontrib>Rao, Shaoqi</creatorcontrib><creatorcontrib>Liao, Xinxue</creatorcontrib><creatorcontrib>Kuang, Jian</creatorcontrib><creatorcontrib>Dai, Gang</creatorcontrib><creatorcontrib>Mai, Weiyi</creatorcontrib><title>Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction</title><title>Acta biochimica et biophysica Sinica</title><addtitle>Acta Biochimica et Biophysica Sinica</addtitle><description>Mesenchymal stem cells （MSCs） have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction （AMI）. However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells （ASCs）, and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 （a transcription factor） and cardiac troponin-I were detected by cellular immuno-fluorescence. Atorvastatin （Ator group） or vehicle （control group） was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 x 106 co-ASCs/100 μl phosphate-buffered saline （PBS）, 1×10^6 ASCs/100 μl PBS, or 100 μl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-I was 22.8%±3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines （VCAM-1, TNF-α, Hs-CRP） mRNA expression, and Bax protein expression were sig- nificantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function （P〈0.05）. Compared with the Ator2 ＋ ASCs group and Con ＋ co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 ＋ co-ASCs group （P〈 0.05）. Pre-amelio-ration of the cardiac milieu, in conjunction with prespecification of ASCs, was beneficial for enhancing ASCs＇ therapeutic efficacy on cardiac function after AMI.</description><subject>Adipose Tissue - cytology</subject><subject>Adipose Tissue - transplantation</subject><subject>Animals</subject><subject>Atorvastatin Calcium</subject><subject>bcl-2-Associated X Protein - drug effects</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Disease Models, Animal</subject><subject>GATA4 Transcription Factor - metabolism</subject><subject>Heart Function Tests</subject><subject>Heptanoic Acids - pharmacology</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Myocardial Infarction - metabolism</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-2 - drug effects</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Pyrroles - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Troponin I - metabolism</subject><subject>Tumor Necrosis Factor-alpha - drug effects</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Vascular Cell Adhesion Molecule-1 - drug effects</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><subject>大鼠</subject><subject>心肌肌钙蛋白I</subject><subject>心脏功能</subject><subject>急性心肌梗死</subject><subject>疗效</subject><subject>细胞移植</subject><subject>脂肪来源</subject><subject>间充质干细胞</subject><issn>1672-9145</issn><issn>1745-7270</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFr1TAUx4sobk6ffJf4ooLUnTRJ0zyOsU1h4Is-l9M0uTfSJl2SbtyP4re1Xa97VDiQwzk_fofwL4q3FL5QUOwcuy6d78YIjXxWnFLJRSkrCc-XvpZVqSgXJ8WrlH4BsLqm8LI4qahqWC2a0-L3lbVOoz6QYMlFDvEeU8bsPNFh7Jw3PXlweU-wd1NIpuxNdPfLcDTJeL0_jDiQlM1ItBkGkiP6NA3oV0XwZCmNsXeoiZ29fpwt6og5HbV6zoaMh7Bhw7K1GB_B18ULi0Myb47vWfHz-urH5dfy9vvNt8uL21JzKnLZc0mpoFJY0JVWpkLk1ihlUAGDinEuuoozkIqhRWb7etmBpLUWrAFVsbPi4-adYribTcrt6NL6G_QmzKlVAFIKkGIhP_2TpE3FFK-VWNHPG6pjSCka207RjRgPLYV2Ta1dU2u31Bb63VE8d6Ppn9i_MS3Ahw0I8_Qf0_vj3X3wuzvnd084Bwqcsob9AUtArwg</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Cai, Anping</creator><creator>Zheng, Dongdan</creator><creator>Dong, Yugang</creator><creator>Qiu, Ruofeng</creator><creator>Huang, Yuli</creator><creator>Song, Yuanbin</creator><creator>Jiang, Zhigao</creator><creator>Rao, Shaoqi</creator><creator>Liao, Xinxue</creator><creator>Kuang, Jian</creator><creator>Dai, Gang</creator><creator>Mai, Weiyi</creator><general>Oxford University Press</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W94</scope><scope>WU4</scope><scope>~WA</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20111101</creationdate><title>Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction</title><author>Cai, Anping ; Zheng, Dongdan ; Dong, Yugang ; Qiu, Ruofeng ; Huang, Yuli ; Song, Yuanbin ; Jiang, Zhigao ; Rao, Shaoqi ; Liao, Xinxue ; Kuang, Jian ; Dai, Gang ; Mai, Weiyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-d47115175f0c2c9e2aa4fe99ea903023445b2430793afa3fd699e0716c5380923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adipose Tissue - cytology</topic><topic>Adipose Tissue - transplantation</topic><topic>Animals</topic><topic>Atorvastatin Calcium</topic><topic>bcl-2-Associated X Protein - drug effects</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Disease Models, Animal</topic><topic>GATA4 Transcription Factor - metabolism</topic><topic>Heart Function Tests</topic><topic>Heptanoic Acids - pharmacology</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Myocardial Infarction - metabolism</topic><topic>Myocardial Infarction - therapy</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Proto-Oncogene Proteins c-bcl-2 - drug effects</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Pyrroles - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Troponin I - metabolism</topic><topic>Tumor Necrosis Factor-alpha - drug effects</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Vascular Cell Adhesion Molecule-1 - drug effects</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><topic>大鼠</topic><topic>心肌肌钙蛋白I</topic><topic>心脏功能</topic><topic>急性心肌梗死</topic><topic>疗效</topic><topic>细胞移植</topic><topic>脂肪来源</topic><topic>间充质干细胞</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Anping</creatorcontrib><creatorcontrib>Zheng, Dongdan</creatorcontrib><creatorcontrib>Dong, Yugang</creatorcontrib><creatorcontrib>Qiu, Ruofeng</creatorcontrib><creatorcontrib>Huang, Yuli</creatorcontrib><creatorcontrib>Song, Yuanbin</creatorcontrib><creatorcontrib>Jiang, Zhigao</creatorcontrib><creatorcontrib>Rao, Shaoqi</creatorcontrib><creatorcontrib>Liao, Xinxue</creatorcontrib><creatorcontrib>Kuang, Jian</creatorcontrib><creatorcontrib>Dai, Gang</creatorcontrib><creatorcontrib>Mai, Weiyi</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-自然科学</collection><collection>中文科技期刊数据库-自然科学-生物科学</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biochimica et biophysica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Anping</au><au>Zheng, Dongdan</au><au>Dong, Yugang</au><au>Qiu, Ruofeng</au><au>Huang, Yuli</au><au>Song, Yuanbin</au><au>Jiang, Zhigao</au><au>Rao, Shaoqi</au><au>Liao, Xinxue</au><au>Kuang, Jian</au><au>Dai, Gang</au><au>Mai, Weiyi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction</atitle><jtitle>Acta biochimica et biophysica Sinica</jtitle><addtitle>Acta Biochimica et Biophysica Sinica</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>43</volume><issue>11</issue><spage>857</spage><epage>866</epage><pages>857-866</pages><issn>1672-9145</issn><eissn>1745-7270</eissn><abstract>Mesenchymal stem cells （MSCs） have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction （AMI）. However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells （ASCs）, and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 （a transcription factor） and cardiac troponin-I were detected by cellular immuno-fluorescence. Atorvastatin （Ator group） or vehicle （control group） was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 x 106 co-ASCs/100 μl phosphate-buffered saline （PBS）, 1×10^6 ASCs/100 μl PBS, or 100 μl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-I was 22.8%±3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines （VCAM-1, TNF-α, Hs-CRP） mRNA expression, and Bax protein expression were sig- nificantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function （P〈0.05）. Compared with the Ator2 ＋ ASCs group and Con ＋ co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 ＋ co-ASCs group （P〈 0.05）. Pre-amelio-ration of the cardiac milieu, in conjunction with prespecification of ASCs, was beneficial for enhancing ASCs＇ therapeutic efficacy on cardiac function after AMI.</abstract><cop>China</cop><pub>Oxford University Press</pub><pmid>21983658</pmid><doi>10.1093/abbs/gmr087</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1672-9145 |
| ispartof | Acta biochimica et biophysica Sinica, 2011-11, Vol.43 (11), p.857-866 |
| issn | 1672-9145 1745-7270 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adipose Tissue - cytology Adipose Tissue - transplantation Animals Atorvastatin Calcium bcl-2-Associated X Protein - drug effects bcl-2-Associated X Protein - metabolism Cell Differentiation - drug effects Cell Proliferation - drug effects Cells, Cultured Coculture Techniques Disease Models, Animal GATA4 Transcription Factor - metabolism Heart Function Tests Heptanoic Acids - pharmacology Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stromal Cells - metabolism Myocardial Infarction - metabolism Myocardial Infarction - therapy Myocytes, Cardiac - metabolism Proto-Oncogene Proteins c-bcl-2 - drug effects Proto-Oncogene Proteins c-bcl-2 - metabolism Pyrroles - pharmacology Rats Rats, Sprague-Dawley Troponin I - metabolism Tumor Necrosis Factor-alpha - drug effects Tumor Necrosis Factor-alpha - metabolism Vascular Cell Adhesion Molecule-1 - drug effects Vascular Cell Adhesion Molecule-1 - metabolism 大鼠 心肌肌钙蛋白I 心脏功能 急性心肌梗死 疗效 细胞移植 脂肪来源 间充质干细胞 |
| title | Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction |
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