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Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest
Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer,...
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| Published in: | Critical care (London, England) England), 2013-10, Vol.17 (5), p.R245-R245, Article R245 |
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| creator | Rungatscher, Alessio Hallström, Seth Giacomazzi, Alice Linardi, Daniele Milani, Elisabetta Tessari, Maddalena Luciani, Giovanni Battista Scarabelli, Tiziano M Mazzucco, Alessandro Faggian, Giuseppe |
| description | Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.
Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.
The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P |
| doi_str_mv | 10.1186/cc13071 |
| format | article |
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Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.
The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.
Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.</description><identifier>ISSN: 1364-8535</identifier><identifier>EISSN: 1466-609X</identifier><identifier>EISSN: 1364-8535</identifier><identifier>DOI: 10.1186/cc13071</identifier><identifier>PMID: 24138817</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Blotting, Western ; Cardiac arrest ; Cardiomyopathy ; Cardiopulmonary Bypass ; Care and treatment ; Circulatory Arrest, Deep Hypothermia Induced ; Drug sensitization ; Epinephrine - pharmacology ; Heart - drug effects ; Heart diseases ; Hemodynamics - drug effects ; Hydrazones - pharmacology ; Immunoenzyme Techniques ; Lactates ; Male ; Phosphorylation ; Pyridazines - pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Rewarming ; Troponin I - blood</subject><ispartof>Critical care (London, England), 2013-10, Vol.17 (5), p.R245-R245, Article R245</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>Copyright © 2013 Rungatscher et al.; licensee BioMed Central Ltd. 2013 Rungatscher et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b487t-c56c84a1e583f8bc8e803b3c0c72f7ad09ee3e5e44a2dcbc616909578403f5d73</citedby><cites>FETCH-LOGICAL-b487t-c56c84a1e583f8bc8e803b3c0c72f7ad09ee3e5e44a2dcbc616909578403f5d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056352/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056352/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24138817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rungatscher, Alessio</creatorcontrib><creatorcontrib>Hallström, Seth</creatorcontrib><creatorcontrib>Giacomazzi, Alice</creatorcontrib><creatorcontrib>Linardi, Daniele</creatorcontrib><creatorcontrib>Milani, Elisabetta</creatorcontrib><creatorcontrib>Tessari, Maddalena</creatorcontrib><creatorcontrib>Luciani, Giovanni Battista</creatorcontrib><creatorcontrib>Scarabelli, Tiziano M</creatorcontrib><creatorcontrib>Mazzucco, Alessandro</creatorcontrib><creatorcontrib>Faggian, Giuseppe</creatorcontrib><title>Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest</title><title>Critical care (London, England)</title><addtitle>Crit Care</addtitle><description>Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.
Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.
The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.
Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cardiac arrest</subject><subject>Cardiomyopathy</subject><subject>Cardiopulmonary Bypass</subject><subject>Care and treatment</subject><subject>Circulatory Arrest, Deep Hypothermia Induced</subject><subject>Drug sensitization</subject><subject>Epinephrine - pharmacology</subject><subject>Heart - drug effects</subject><subject>Heart diseases</subject><subject>Hemodynamics - drug effects</subject><subject>Hydrazones - pharmacology</subject><subject>Immunoenzyme Techniques</subject><subject>Lactates</subject><subject>Male</subject><subject>Phosphorylation</subject><subject>Pyridazines - pharmacology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rewarming</subject><subject>Troponin I - blood</subject><issn>1364-8535</issn><issn>1466-609X</issn><issn>1364-8535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp1kl2L1TAQhoso7ofiP5CCF3rTNWk-64WwLK4KC4IoeBfS6WRPpG2OSSrUX2-O57jsASUXCZnnfWcymap6RskFpVq-BqCMKPqgOqVcykaS7tvDcmaSN1owcVKdpfSdEKq0ZI-rk5ZTpjVVp1X-HEasg6vBjuCXqR4w4Zx89r9s9mGu_VznDdY5os0TznnHTmsAGwdvx3pYk1tm-INalzEWA9zWm3UbiixOHmrwEZbR5hDX2saIKT-pHjk7Jnx62M-rr9fvvlx9aG4-vf94dXnT9Fyr3ICQoLmlKDRzugeNmrCeAQHVOmUH0iEyFMi5bQfoQVLZkU4ozQlzYlDsvHq7990u_YQDlPKjHc02-snG1QTrzXFk9htzG34aToRkoi0Gb_YGvQ__MTiOQJjM4S-K-NUheww_lvJsM_kEOI52xrAkQ4XoJFWEdwV9sUdv7YjGzy4UN9jh5lIwrpRupSjUxT-osgYsfQ4zOl_ujwQv9wKIIaWI7q5ySsxubu7V-vx-p-64v4PCfgPMacGd</recordid><startdate>20131020</startdate><enddate>20131020</enddate><creator>Rungatscher, Alessio</creator><creator>Hallström, Seth</creator><creator>Giacomazzi, Alice</creator><creator>Linardi, Daniele</creator><creator>Milani, Elisabetta</creator><creator>Tessari, Maddalena</creator><creator>Luciani, Giovanni Battista</creator><creator>Scarabelli, Tiziano M</creator><creator>Mazzucco, Alessandro</creator><creator>Faggian, Giuseppe</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><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>5PM</scope></search><sort><creationdate>20131020</creationdate><title>Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest</title><author>Rungatscher, Alessio ; Hallström, Seth ; Giacomazzi, Alice ; Linardi, Daniele ; Milani, Elisabetta ; Tessari, Maddalena ; Luciani, Giovanni Battista ; Scarabelli, Tiziano M ; Mazzucco, Alessandro ; Faggian, Giuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b487t-c56c84a1e583f8bc8e803b3c0c72f7ad09ee3e5e44a2dcbc616909578403f5d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cardiac arrest</topic><topic>Cardiomyopathy</topic><topic>Cardiopulmonary Bypass</topic><topic>Care and treatment</topic><topic>Circulatory Arrest, Deep Hypothermia Induced</topic><topic>Drug sensitization</topic><topic>Epinephrine - pharmacology</topic><topic>Heart - drug effects</topic><topic>Heart diseases</topic><topic>Hemodynamics - drug effects</topic><topic>Hydrazones - pharmacology</topic><topic>Immunoenzyme Techniques</topic><topic>Lactates</topic><topic>Male</topic><topic>Phosphorylation</topic><topic>Pyridazines - pharmacology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rewarming</topic><topic>Troponin I - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rungatscher, Alessio</creatorcontrib><creatorcontrib>Hallström, Seth</creatorcontrib><creatorcontrib>Giacomazzi, Alice</creatorcontrib><creatorcontrib>Linardi, Daniele</creatorcontrib><creatorcontrib>Milani, Elisabetta</creatorcontrib><creatorcontrib>Tessari, Maddalena</creatorcontrib><creatorcontrib>Luciani, Giovanni Battista</creatorcontrib><creatorcontrib>Scarabelli, Tiziano M</creatorcontrib><creatorcontrib>Mazzucco, Alessandro</creatorcontrib><creatorcontrib>Faggian, Giuseppe</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Critical care (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rungatscher, Alessio</au><au>Hallström, Seth</au><au>Giacomazzi, Alice</au><au>Linardi, Daniele</au><au>Milani, Elisabetta</au><au>Tessari, Maddalena</au><au>Luciani, Giovanni Battista</au><au>Scarabelli, Tiziano M</au><au>Mazzucco, Alessandro</au><au>Faggian, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest</atitle><jtitle>Critical care (London, England)</jtitle><addtitle>Crit Care</addtitle><date>2013-10-20</date><risdate>2013</risdate><volume>17</volume><issue>5</issue><spage>R245</spage><epage>R245</epage><pages>R245-R245</pages><artnum>R245</artnum><issn>1364-8535</issn><eissn>1466-609X</eissn><eissn>1364-8535</eissn><abstract>Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.
Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.
The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.
Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24138817</pmid><doi>10.1186/cc13071</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blotting, Western Cardiac arrest Cardiomyopathy Cardiopulmonary Bypass Care and treatment Circulatory Arrest, Deep Hypothermia Induced Drug sensitization Epinephrine - pharmacology Heart - drug effects Heart diseases Hemodynamics - drug effects Hydrazones - pharmacology Immunoenzyme Techniques Lactates Male Phosphorylation Pyridazines - pharmacology Random Allocation Rats Rats, Wistar Rewarming Troponin I - blood |
| title | Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
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