Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application
Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 1...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1988-10, Vol.78 (4), p.1008-1019 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | MINARDO, J. D TULI, M. M MOCK, B. H WEINER, R. E PRIDE, H. P WELLMAN, H. N ZIPES, D. P |
| description | Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs. |
| doi_str_mv | 10.1161/01.cir.78.4.1008 |
| format | Article |
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D ; TULI, M. M ; MOCK, B. H ; WEINER, R. E ; PRIDE, H. P ; WELLMAN, H. N ; ZIPES, D. P</creator><creatorcontrib>MINARDO, J. D ; TULI, M. M ; MOCK, B. H ; WEINER, R. E ; PRIDE, H. P ; WELLMAN, H. N ; ZIPES, D. P ; Indiana Univ. School of Medicine, Indianapolis (USA)</creatorcontrib><description>Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.78.4.1008</identifier><identifier>PMID: 3168182</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>3-Iodobenzylguanidine ; 550601 - Medicine- Unsealed Radionuclides in Diagnostics ; 560300 - Chemicals Metabolism & Toxicology ; ANIMALS ; AROMATICS ; BETA DECAY RADIOISOTOPES ; Biological and medical sciences ; BIOLOGICAL EFFECTS ; BIOLOGICAL RECOVERY ; BIOLOGICAL REGENERATION ; BODY ; Cardiology. Vascular system ; CARDIOVASCULAR DISEASES ; CARDIOVASCULAR SYSTEM ; Coronary heart disease ; COUNTING TECHNIQUES ; DIAGNOSTIC TECHNIQUES ; DISEASES ; DOGS ; DRUGS ; ELECTRON CAPTURE RADIOISOTOPES ; ELECTROPHYSIOLOGY ; Female ; HEART ; Heart - diagnostic imaging ; Heart - innervation ; HOURS LIVING RADIOISOTOPES ; HYDROXY COMPOUNDS ; IMAGE PROCESSING ; INTERMEDIATE MASS NUCLEI ; IODINE 123 ; IODINE ISOTOPES ; Iodine Radioisotopes ; Iodobenzenes ; ISOTOPES ; LABELLED COMPOUNDS ; Male ; MAMMALS ; Medical sciences ; MYOCARDIAL INFARCTION ; Myocardial Infarction - diagnostic imaging ; Nerve Regeneration ; NERVES ; NERVOUS SYSTEM ; NUCLEI ; ODD-EVEN NUCLEI ; ORGANIC COMPOUNDS ; ORGANS ; PERFUSED ORGANS ; PHENOLS ; Phenols - pharmacology ; PHYSIOLOGY ; PROCESSING ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; RADIOISOTOPE SCANNING ; RADIOISOTOPES ; RADIOLOGY AND NUCLEAR MEDICINE ; Radionuclide Imaging ; RADIOPHARMACEUTICALS ; RECOVERY ; SCINTISCANNING ; Sympathetic Nervous System - physiology ; Thallium Radioisotopes ; VERTEBRATES</subject><ispartof>Circulation (New York, N.Y.), 1988-10, Vol.78 (4), p.1008-1019</ispartof><rights>1989 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-6f325586452b404050f477fb115a30248331d5ce509e0eafe69366e32287b743</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,885,3685,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7006668$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3168182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/6558295$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>MINARDO, J. D</creatorcontrib><creatorcontrib>TULI, M. M</creatorcontrib><creatorcontrib>MOCK, B. H</creatorcontrib><creatorcontrib>WEINER, R. E</creatorcontrib><creatorcontrib>PRIDE, H. P</creatorcontrib><creatorcontrib>WELLMAN, H. N</creatorcontrib><creatorcontrib>ZIPES, D. P</creatorcontrib><creatorcontrib>Indiana Univ. School of Medicine, Indianapolis (USA)</creatorcontrib><title>Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.</description><subject>3-Iodobenzylguanidine</subject><subject>550601 - Medicine- Unsealed Radionuclides in Diagnostics</subject><subject>560300 - Chemicals Metabolism & Toxicology</subject><subject>ANIMALS</subject><subject>AROMATICS</subject><subject>BETA DECAY RADIOISOTOPES</subject><subject>Biological and medical sciences</subject><subject>BIOLOGICAL EFFECTS</subject><subject>BIOLOGICAL RECOVERY</subject><subject>BIOLOGICAL REGENERATION</subject><subject>BODY</subject><subject>Cardiology. Vascular system</subject><subject>CARDIOVASCULAR DISEASES</subject><subject>CARDIOVASCULAR SYSTEM</subject><subject>Coronary heart disease</subject><subject>COUNTING TECHNIQUES</subject><subject>DIAGNOSTIC TECHNIQUES</subject><subject>DISEASES</subject><subject>DOGS</subject><subject>DRUGS</subject><subject>ELECTRON CAPTURE RADIOISOTOPES</subject><subject>ELECTROPHYSIOLOGY</subject><subject>Female</subject><subject>HEART</subject><subject>Heart - diagnostic imaging</subject><subject>Heart - innervation</subject><subject>HOURS LIVING RADIOISOTOPES</subject><subject>HYDROXY COMPOUNDS</subject><subject>IMAGE PROCESSING</subject><subject>INTERMEDIATE MASS NUCLEI</subject><subject>IODINE 123</subject><subject>IODINE ISOTOPES</subject><subject>Iodine Radioisotopes</subject><subject>Iodobenzenes</subject><subject>ISOTOPES</subject><subject>LABELLED COMPOUNDS</subject><subject>Male</subject><subject>MAMMALS</subject><subject>Medical sciences</subject><subject>MYOCARDIAL INFARCTION</subject><subject>Myocardial Infarction - diagnostic imaging</subject><subject>Nerve Regeneration</subject><subject>NERVES</subject><subject>NERVOUS SYSTEM</subject><subject>NUCLEI</subject><subject>ODD-EVEN NUCLEI</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANS</subject><subject>PERFUSED ORGANS</subject><subject>PHENOLS</subject><subject>Phenols - pharmacology</subject><subject>PHYSIOLOGY</subject><subject>PROCESSING</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>RADIOISOTOPE SCANNING</subject><subject>RADIOISOTOPES</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>Radionuclide Imaging</subject><subject>RADIOPHARMACEUTICALS</subject><subject>RECOVERY</subject><subject>SCINTISCANNING</subject><subject>Sympathetic Nervous System - physiology</subject><subject>Thallium Radioisotopes</subject><subject>VERTEBRATES</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkV-L1DAUxYMo6-zquy9CEfGtNWn-tH2UYXUXFgTd95De3m4jbVKTzEK_kJ_TzM6wCoGQe8793SSHkHeMVowp9pmyCmyomrYSFaO0fUF2TNaiFJJ3L8mOUtqVDa_r1-Qyxl_5qHgjL8gFZ6plbb0jf36Cdck-BLNOFgrjhgJnhBT8Om3R-tk_WDBzgY92QAdY-LEA46zDYtk8mDDYrMZtWU2aMGVEtmF4NMl694QLaN2_yhr8cAAcin77H2DdaAI8OXwo1gmdnwuzrnMefqy-Ia9GM0d8e96vyP3X6_v9TXn3_dvt_stdCaLrUqlGXkvZKiHrXlBBJR1F04w9Y9JwWouWczZIQEk7pGhGVB1XCvMHtU3fCH5FPpywPiarI9iEMIHP94ekVSbXncymTydTfsvvA8akFxsB59k49Ieom1aIvI40ejJC8DEGHPUa7GLCphnVx_g0ZXp_-yN3aKGP8eWW92f2oV9weG4455X1j2fdxBzLGIwDG59tTQ5YqZb_Bdh9pp8</recordid><startdate>19881001</startdate><enddate>19881001</enddate><creator>MINARDO, J. D</creator><creator>TULI, M. M</creator><creator>MOCK, B. H</creator><creator>WEINER, R. E</creator><creator>PRIDE, H. P</creator><creator>WELLMAN, H. N</creator><creator>ZIPES, D. P</creator><general>Lippincott Williams & Wilkins</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><scope>OTOTI</scope></search><sort><creationdate>19881001</creationdate><title>Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application</title><author>MINARDO, J. D ; TULI, M. M ; MOCK, B. H ; WEINER, R. E ; PRIDE, H. P ; WELLMAN, H. N ; ZIPES, D. P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-6f325586452b404050f477fb115a30248331d5ce509e0eafe69366e32287b743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>3-Iodobenzylguanidine</topic><topic>550601 - Medicine- Unsealed Radionuclides in Diagnostics</topic><topic>560300 - Chemicals Metabolism & Toxicology</topic><topic>ANIMALS</topic><topic>AROMATICS</topic><topic>BETA DECAY RADIOISOTOPES</topic><topic>Biological and medical sciences</topic><topic>BIOLOGICAL EFFECTS</topic><topic>BIOLOGICAL RECOVERY</topic><topic>BIOLOGICAL REGENERATION</topic><topic>BODY</topic><topic>Cardiology. Vascular system</topic><topic>CARDIOVASCULAR DISEASES</topic><topic>CARDIOVASCULAR SYSTEM</topic><topic>Coronary heart disease</topic><topic>COUNTING TECHNIQUES</topic><topic>DIAGNOSTIC TECHNIQUES</topic><topic>DISEASES</topic><topic>DOGS</topic><topic>DRUGS</topic><topic>ELECTRON CAPTURE RADIOISOTOPES</topic><topic>ELECTROPHYSIOLOGY</topic><topic>Female</topic><topic>HEART</topic><topic>Heart - diagnostic imaging</topic><topic>Heart - innervation</topic><topic>HOURS LIVING RADIOISOTOPES</topic><topic>HYDROXY COMPOUNDS</topic><topic>IMAGE PROCESSING</topic><topic>INTERMEDIATE MASS NUCLEI</topic><topic>IODINE 123</topic><topic>IODINE ISOTOPES</topic><topic>Iodine Radioisotopes</topic><topic>Iodobenzenes</topic><topic>ISOTOPES</topic><topic>LABELLED COMPOUNDS</topic><topic>Male</topic><topic>MAMMALS</topic><topic>Medical sciences</topic><topic>MYOCARDIAL INFARCTION</topic><topic>Myocardial Infarction - diagnostic imaging</topic><topic>Nerve Regeneration</topic><topic>NERVES</topic><topic>NERVOUS SYSTEM</topic><topic>NUCLEI</topic><topic>ODD-EVEN NUCLEI</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANS</topic><topic>PERFUSED ORGANS</topic><topic>PHENOLS</topic><topic>Phenols - pharmacology</topic><topic>PHYSIOLOGY</topic><topic>PROCESSING</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>RADIOISOTOPE SCANNING</topic><topic>RADIOISOTOPES</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>Radionuclide Imaging</topic><topic>RADIOPHARMACEUTICALS</topic><topic>RECOVERY</topic><topic>SCINTISCANNING</topic><topic>Sympathetic Nervous System - physiology</topic><topic>Thallium Radioisotopes</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MINARDO, J. D</creatorcontrib><creatorcontrib>TULI, M. M</creatorcontrib><creatorcontrib>MOCK, B. H</creatorcontrib><creatorcontrib>WEINER, R. E</creatorcontrib><creatorcontrib>PRIDE, H. P</creatorcontrib><creatorcontrib>WELLMAN, H. N</creatorcontrib><creatorcontrib>ZIPES, D. P</creatorcontrib><creatorcontrib>Indiana Univ. School of Medicine, Indianapolis (USA)</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><collection>OSTI.GOV</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MINARDO, J. D</au><au>TULI, M. M</au><au>MOCK, B. H</au><au>WEINER, R. E</au><au>PRIDE, H. P</au><au>WELLMAN, H. N</au><au>ZIPES, D. P</au><aucorp>Indiana Univ. School of Medicine, Indianapolis (USA)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1988-10-01</date><risdate>1988</risdate><volume>78</volume><issue>4</issue><spage>1008</spage><epage>1019</epage><pages>1008-1019</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>3168182</pmid><doi>10.1161/01.cir.78.4.1008</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | 3-Iodobenzylguanidine 550601 - Medicine- Unsealed Radionuclides in Diagnostics 560300 - Chemicals Metabolism & Toxicology ANIMALS AROMATICS BETA DECAY RADIOISOTOPES Biological and medical sciences BIOLOGICAL EFFECTS BIOLOGICAL RECOVERY BIOLOGICAL REGENERATION BODY Cardiology. Vascular system CARDIOVASCULAR DISEASES CARDIOVASCULAR SYSTEM Coronary heart disease COUNTING TECHNIQUES DIAGNOSTIC TECHNIQUES DISEASES DOGS DRUGS ELECTRON CAPTURE RADIOISOTOPES ELECTROPHYSIOLOGY Female HEART Heart - diagnostic imaging Heart - innervation HOURS LIVING RADIOISOTOPES HYDROXY COMPOUNDS IMAGE PROCESSING INTERMEDIATE MASS NUCLEI IODINE 123 IODINE ISOTOPES Iodine Radioisotopes Iodobenzenes ISOTOPES LABELLED COMPOUNDS Male MAMMALS Medical sciences MYOCARDIAL INFARCTION Myocardial Infarction - diagnostic imaging Nerve Regeneration NERVES NERVOUS SYSTEM NUCLEI ODD-EVEN NUCLEI ORGANIC COMPOUNDS ORGANS PERFUSED ORGANS PHENOLS Phenols - pharmacology PHYSIOLOGY PROCESSING RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RADIOISOTOPE SCANNING RADIOISOTOPES RADIOLOGY AND NUCLEAR MEDICINE Radionuclide Imaging RADIOPHARMACEUTICALS RECOVERY SCINTISCANNING Sympathetic Nervous System - physiology Thallium Radioisotopes VERTEBRATES |
| title | Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application |
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