Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia
The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in b...
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| Veröffentlicht in: | British journal of anaesthesia : BJA 2003-08, Vol.91 (2), p.281 |
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| creator | Gerbershagen, M U Wappler, F Fiege, M Kolodzie, K Weisshorn, R Szafarczyk, W Kudlik, C Schulte Am Esch, J |
| description | The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated.
and results. DOI 1 mg kg(-1) was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (Pa(CO(2))), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by Pa(CO(2)) above 70 mm Hg and an increase in body temperature of more than 2 degrees C. Intragroup differences were analysed with the Friedman test as an overall non-parametric ANOVA and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann-Whitney U-test (statistical significance P |
| doi_str_mv | 10.1093/bja/aeg172 |
| format | Article |
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and results. DOI 1 mg kg(-1) was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (Pa(CO(2))), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by Pa(CO(2)) above 70 mm Hg and an increase in body temperature of more than 2 degrees C. Intragroup differences were analysed with the Friedman test as an overall non-parametric ANOVA and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann-Whitney U-test (statistical significance P<0.05). MHS and MHN pigs developed muscle fasciculations, significant increases in body temperature and Pa(CO(2)) and a significant decrease in pH after the administration of DOI. These changes were comparable in both groups until the third dose of DOI, when in MHS pigs heart rate and Pa(CO(2)) rose significantly and pH fell significantly compared with MHN pigs. All MHS pigs fulfilled the MH criteria. Body temperature increased by more than 2 degrees C in all MHN pigs and Pa(CO(2)) exceeded 70 mm Hg in two. Thus, two MHN pigs fulfilled the criteria of MH.
The comparability of the clinical presentation following DOI administration in MHS and MHN animals and the order of the development of MH-like symptoms favour the hypothesis of a central serotonergic overstimulation, leading to a serotonin syndrome.</description><identifier>ISSN: 0007-0912</identifier><identifier>EISSN: 1471-6771</identifier><identifier>DOI: 10.1093/bja/aeg172</identifier><identifier>PMID: 12878630</identifier><identifier>CODEN: BJANAD</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Amphetamines - adverse effects ; Animals ; Carbon Dioxide - blood ; Disease Susceptibility ; Malignant Hyperthermia - etiology ; Malignant Hyperthermia - physiopathology ; Partial Pressure ; Receptors, Serotonin - physiology ; Serotonin Receptor Agonists - adverse effects ; Serotonin Syndrome - chemically induced ; Swine</subject><ispartof>British journal of anaesthesia : BJA, 2003-08, Vol.91 (2), p.281</ispartof><rights>Copyright British Medical Association Aug 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12878630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gerbershagen, M U</creatorcontrib><creatorcontrib>Wappler, F</creatorcontrib><creatorcontrib>Fiege, M</creatorcontrib><creatorcontrib>Kolodzie, K</creatorcontrib><creatorcontrib>Weisshorn, R</creatorcontrib><creatorcontrib>Szafarczyk, W</creatorcontrib><creatorcontrib>Kudlik, C</creatorcontrib><creatorcontrib>Schulte Am Esch, J</creatorcontrib><title>Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia</title><title>British journal of anaesthesia : BJA</title><addtitle>Br J Anaesth</addtitle><description>The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated.
and results. DOI 1 mg kg(-1) was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (Pa(CO(2))), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by Pa(CO(2)) above 70 mm Hg and an increase in body temperature of more than 2 degrees C. Intragroup differences were analysed with the Friedman test as an overall non-parametric ANOVA and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann-Whitney U-test (statistical significance P<0.05). MHS and MHN pigs developed muscle fasciculations, significant increases in body temperature and Pa(CO(2)) and a significant decrease in pH after the administration of DOI. These changes were comparable in both groups until the third dose of DOI, when in MHS pigs heart rate and Pa(CO(2)) rose significantly and pH fell significantly compared with MHN pigs. All MHS pigs fulfilled the MH criteria. Body temperature increased by more than 2 degrees C in all MHN pigs and Pa(CO(2)) exceeded 70 mm Hg in two. Thus, two MHN pigs fulfilled the criteria of MH.
The comparability of the clinical presentation following DOI administration in MHS and MHN animals and the order of the development of MH-like symptoms favour the hypothesis of a central serotonergic overstimulation, leading to a serotonin syndrome.</description><subject>Amphetamines - adverse effects</subject><subject>Animals</subject><subject>Carbon Dioxide - blood</subject><subject>Disease Susceptibility</subject><subject>Malignant Hyperthermia - etiology</subject><subject>Malignant Hyperthermia - physiopathology</subject><subject>Partial Pressure</subject><subject>Receptors, Serotonin - physiology</subject><subject>Serotonin Receptor Agonists - adverse effects</subject><subject>Serotonin Syndrome - chemically induced</subject><subject>Swine</subject><issn>0007-0912</issn><issn>1471-6771</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo10LFOwzAQBmALgWgpLDwAsphgCPXZjl2PqCoUqRJLmYOTXNJUTRxsZyhPTxBlun_4dPfrCLkF9gTMiHm-t3OLNWh-RqYgNSRKazgnU8aYTpgBPiFXIewZG4lJL8kE-EIvlGBT8rmqKixioK6ilqbr7QN_pB4L7KPz1Naua0KkrqO2sxjiDmPzjSXtmzrQMIRf1-QHpNHR1h6aurNdpLtjj360vm3sNbmo7CHgzWnOyMfLartcJ5v317fl8ybpQamYgLIpMmGQc80kLwshS4HIAVk-ZmEEFEqmwkpAqLTSgkktU27xV2olZuT-b2_v3dcwVs32bvDdeDIDoxcGhOEjujuhIW-xzHrftNYfs_9_iB88ZWDN</recordid><startdate>200308</startdate><enddate>200308</enddate><creator>Gerbershagen, M U</creator><creator>Wappler, F</creator><creator>Fiege, M</creator><creator>Kolodzie, K</creator><creator>Weisshorn, R</creator><creator>Szafarczyk, W</creator><creator>Kudlik, C</creator><creator>Schulte Am Esch, J</creator><general>Oxford Publishing Limited (England)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>K9.</scope></search><sort><creationdate>200308</creationdate><title>Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia</title><author>Gerbershagen, M U ; Wappler, F ; Fiege, M ; Kolodzie, K ; Weisshorn, R ; Szafarczyk, W ; Kudlik, C ; Schulte Am Esch, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p166t-16a5e039e227042dc34d3ee21e0bc343931c6453a41e1f7673047452aec34d763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amphetamines - adverse effects</topic><topic>Animals</topic><topic>Carbon Dioxide - blood</topic><topic>Disease Susceptibility</topic><topic>Malignant Hyperthermia - etiology</topic><topic>Malignant Hyperthermia - physiopathology</topic><topic>Partial Pressure</topic><topic>Receptors, Serotonin - physiology</topic><topic>Serotonin Receptor Agonists - adverse effects</topic><topic>Serotonin Syndrome - chemically induced</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gerbershagen, M U</creatorcontrib><creatorcontrib>Wappler, F</creatorcontrib><creatorcontrib>Fiege, M</creatorcontrib><creatorcontrib>Kolodzie, K</creatorcontrib><creatorcontrib>Weisshorn, R</creatorcontrib><creatorcontrib>Szafarczyk, W</creatorcontrib><creatorcontrib>Kudlik, C</creatorcontrib><creatorcontrib>Schulte Am Esch, J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>British journal of anaesthesia : BJA</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gerbershagen, M U</au><au>Wappler, F</au><au>Fiege, M</au><au>Kolodzie, K</au><au>Weisshorn, R</au><au>Szafarczyk, W</au><au>Kudlik, C</au><au>Schulte Am Esch, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia</atitle><jtitle>British journal of anaesthesia : BJA</jtitle><addtitle>Br J Anaesth</addtitle><date>2003-08</date><risdate>2003</risdate><volume>91</volume><issue>2</issue><spage>281</spage><pages>281-</pages><issn>0007-0912</issn><eissn>1471-6771</eissn><coden>BJANAD</coden><abstract>The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated.
and results. DOI 1 mg kg(-1) was administered three times at 40-min intervals to five MHS and five MHN anaesthetized pigs. Body temperature, heart rate, muscle tone, arterial carbon dioxide pressure (Pa(CO(2))), pH and creatine kinase concentrations were measured. The clinical occurrence of MH was defined by Pa(CO(2)) above 70 mm Hg and an increase in body temperature of more than 2 degrees C. Intragroup differences were analysed with the Friedman test as an overall non-parametric ANOVA and, in case of significance, with the Wilcoxon test. Intergroup comparisons were performed with the Mann-Whitney U-test (statistical significance P<0.05). MHS and MHN pigs developed muscle fasciculations, significant increases in body temperature and Pa(CO(2)) and a significant decrease in pH after the administration of DOI. These changes were comparable in both groups until the third dose of DOI, when in MHS pigs heart rate and Pa(CO(2)) rose significantly and pH fell significantly compared with MHN pigs. All MHS pigs fulfilled the MH criteria. Body temperature increased by more than 2 degrees C in all MHN pigs and Pa(CO(2)) exceeded 70 mm Hg in two. Thus, two MHN pigs fulfilled the criteria of MH.
The comparability of the clinical presentation following DOI administration in MHS and MHN animals and the order of the development of MH-like symptoms favour the hypothesis of a central serotonergic overstimulation, leading to a serotonin syndrome.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>12878630</pmid><doi>10.1093/bja/aeg172</doi></addata></record> |
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| subjects | Amphetamines - adverse effects Animals Carbon Dioxide - blood Disease Susceptibility Malignant Hyperthermia - etiology Malignant Hyperthermia - physiopathology Partial Pressure Receptors, Serotonin - physiology Serotonin Receptor Agonists - adverse effects Serotonin Syndrome - chemically induced Swine |
| title | Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia |
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