Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts

Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minu...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 1997-11, Vol.96 (9), p.3094-3103
Hauptverfasser: SOMMERSCHILD, H. T, GRUND, F, OFFSTAD, J, JYNGE, P, ILEBEKK, A, KIRKEBØEN, K. A
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container_end_page 3103
container_issue 9
container_start_page 3094
container_title Circulation (New York, N.Y.)
container_volume 96
creator SOMMERSCHILD, H. T
GRUND, F
OFFSTAD, J
JYNGE, P
ILEBEKK, A
KIRKEBØEN, K. A
description Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P
doi_str_mv 10.1161/01.CIR.96.9.3094
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T ; GRUND, F ; OFFSTAD, J ; JYNGE, P ; ILEBEKK, A ; KIRKEBØEN, K. A</creator><creatorcontrib>SOMMERSCHILD, H. T ; GRUND, F ; OFFSTAD, J ; JYNGE, P ; ILEBEKK, A ; KIRKEBØEN, K. A</creatorcontrib><description>Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P&lt;.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P&lt;.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P&lt;.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P&lt;.05). In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.96.9.3094</identifier><identifier>PMID: 9386180</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams &amp; Wilkins</publisher><subject>Adenosine - physiology ; Animals ; Animals, Newborn ; Biological and medical sciences ; Cardiology. 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In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P&lt;.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P&lt;.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P&lt;.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P&lt;.05). 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Vascular system</subject><subject>Coronary heart disease</subject><subject>Creatine Kinase - metabolism</subject><subject>Heart</subject><subject>Medical sciences</subject><subject>Myocardial Contraction</subject><subject>Myocardial Ischemia - physiopathology</subject><subject>Myocardial Reperfusion</subject><subject>Piperazines - pharmacology</subject><subject>Swine</subject><subject>Theophylline - analogs &amp; derivatives</subject><subject>Theophylline - pharmacology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkM1r3DAUxEVpSbZJ7r0ERAm92dGHLVnHsKTtQqAQ0mMRT1-Jgy1tJPuQ_z5asuTQ0_B4vxmGQegbJS2lgl4T2m53960SrWo5Ud0ntKE965qu5-oz2hBCVCM5Y6foaynP9RRc9ifoRPFB0IFs0L_dvE95gWg9TgH76NKjj2ktGFzVMkaP3ZrH-IjHYp_8PAKG6HD2e5_DWsYU8Rhx9CnCAhOuYfbgefKQl3KOvgSYir846hn6-_P2Yfu7ufvza7e9uWssV3RplOuFMNYFgEGA7azypgsghwAsBOOEp1RJaWQvDBgzUCKcJFxSZ43pPeFn6Md77j6nl9WXRc-1rZ8mqMXWoqXquOq7A_j9P_A5rTnWbppRJhnjtKsQeYdsTqVkH_Q-jzPkV02JPsyuCdV1dq2EVvowe7VcHnNXM3v3YTjuXP9Xxz8UC1PIdfCxfGCMCNLXmDe4YYxR</recordid><startdate>19971104</startdate><enddate>19971104</enddate><creator>SOMMERSCHILD, H. 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T</creatorcontrib><creatorcontrib>GRUND, F</creatorcontrib><creatorcontrib>OFFSTAD, J</creatorcontrib><creatorcontrib>JYNGE, P</creatorcontrib><creatorcontrib>ILEBEKK, A</creatorcontrib><creatorcontrib>KIRKEBØEN, K. A</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>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SOMMERSCHILD, H. T</au><au>GRUND, F</au><au>OFFSTAD, J</au><au>JYNGE, P</au><au>ILEBEKK, A</au><au>KIRKEBØEN, K. A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1997-11-04</date><risdate>1997</risdate><volume>96</volume><issue>9</issue><spage>3094</spage><epage>3103</epage><pages>3094-3103</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P&lt;.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P&lt;.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P&lt;.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P&lt;.05). In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>9386180</pmid><doi>10.1161/01.CIR.96.9.3094</doi><tpages>10</tpages></addata></record>
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source MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete
subjects Adenosine - physiology
Animals
Animals, Newborn
Biological and medical sciences
Cardiology. Vascular system
Coronary heart disease
Creatine Kinase - metabolism
Heart
Medical sciences
Myocardial Contraction
Myocardial Ischemia - physiopathology
Myocardial Reperfusion
Piperazines - pharmacology
Swine
Theophylline - analogs & derivatives
Theophylline - pharmacology
title Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts
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