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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1998-8-4
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pubmed:abstractText |
1. Ischaemic cardiac preconditioning represents an important cardioprotective mechanism which limits myocardial ischaemic damage. The aim of this investigation was to assess the impact of dichloroacetate (DCA), a pyruvate dehydrogenase complex activator, on preconditioning. 2. Rat isolated hearts were perfused by use of the Langendorff technique, and were subjected to either preconditioning (3 x 4 or 3 x 6 min ischaemia) or continuous perfusion, followed by 30 min global ischaemia and 60 min reperfusion. DCA (3 mM) was either given throughout the protocol (pretreatment), during reperfusion only (post-treatment), or not at all. Throughout reperfusion mechanical performance was assessed as the rate-pressure product (RPP: left ventricular developed pressure x heart rate). 3. In non-preconditioned control hearts, mechanical performance was substantially (P < 0.001) depressed on reperfusion (the RPP after 60 min of reperfusion (RPP(t=60)) was 4,246+/-974 mmHg beats min(-1) compared to baseline value of 21,297+/-1,728 mmHg beats min(-1)). Preconditioning with either 3 x 4 min or 3 x 6 min cycles caused significant protection, as shown by enhanced recovery (RPP(t=60) = 7,818+/-1,138, P < 0.05, and 11,123+/-587 mmHg beats min(-1), P < 0.001, respectively). 4. Addition of DCA (3 mM) to hearts under baseline conditions significantly (P < 0.001) enhanced systolic function with an increased left ventricular developed pressure of 108+/-5 mmHg compared to 88.3+/-3.0 mmHg in the controls. 5. Pretreatment with 3 mM DCA had no effect on recovery of mechanical performance in the non-preconditioned hearts (RPP(t=60) = 3,640+/-1,235 mmHg beats min(-1)) while the beneficial effects of preconditioning were reduced in the preconditioned hearts (3 x 4 min: RPP(t=60) = 2,919+/-1,060 mmHg beats min(-1); 3 x 6 min: RPP(t=60) = 8,032+/-1,367 mmHg beats min(-1)). Therefore, DCA had increased the threshold for preconditioning. 6. By contrast, post-treatment of hearts with 3 mM DCA substantially improved recovery on reperfusion in all groups (RPP(t=60) = 5,827+/-1,328 (non-preconditioned), 14,022+/-3,743 (3 x 4 min; P < 0.01) and 23,219+/-1,374 (3 x 6 min; P < 0.001) mmHg beats min(-1)). 7. The results of the present investigation clearly show that pretreatment with DCA enhances baseline cardiac mechanical performance but increases the threshold for cardiac preconditioning. However, post-treatment with DCA substantially augments the beneficial effects of preconditioning.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0007-1188
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
124
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
245-51
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:9630366-Animals,
pubmed-meshheading:9630366-Dichloroacetate,
pubmed-meshheading:9630366-Energy Metabolism,
pubmed-meshheading:9630366-Enzyme Activation,
pubmed-meshheading:9630366-Ischemic Preconditioning, Myocardial,
pubmed-meshheading:9630366-Male,
pubmed-meshheading:9630366-Myocardial Ischemia,
pubmed-meshheading:9630366-Pyruvate Dehydrogenase Complex,
pubmed-meshheading:9630366-Rats,
pubmed-meshheading:9630366-Rats, Wistar
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pubmed:year |
1998
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pubmed:articleTitle |
Dual effects of dichloroacetate on cardiac ischaemic preconditioning in the rat isolated perfused heart.
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pubmed:affiliation |
School of Biomedical Sciences, University of Nottingham Medical School.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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