| CARDIAC role of the mitochondrial Ca2+ transporters in the high-[K+](o) cardioprotection of rat hearts under ischemia and reperfusion: a mechano-energetic study. | |
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MedLine Citation:
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PMID: 19597370 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of mitochondrial transporters in the cardioprotection of rat hearts exposed to high [K+]-low [Ca2+]-cardioplegia (CPG) and ischemia and reperfusion (I/R) was studied through the mechano-energetic consequences of target drugs. The total heat rate (Ht) and the left intraventricular pressure (LVP) were simultaneously measured in isolated perfused hearts (30 degrees C and 1 Hz) inside a flow-calorimeter during 45 minutes of no-flow I and 45 minutes of R. After stabilization (C) they were pretreated with CPG and 100 microM 5-hydroxidecanoate (5HD, selective mKATP blocker) without and with 10 or 30 microM clonazepam (Clzp, mNCX inhibitor), 30 microM diazoxide (Dzx, selective mKATP opener), 1 microM Ru360 (selective Ca-uniporter blocker), and 0.2 microM cyclosporine-A, (mPTP inhibitor, before I and during R). Before I, 5-hydroxydecanoate in CPG increased the resting heat rate (17.83 +/- 3.55 mW/g) without changing the stunning. Clzp 30 microM + CPG + 5-hydroxydecanoate reduced the postischemic P with diastolic contracture and high Ht. Dzx protected C-hearts from stunning but increased it in CPG hearts with low economy (P/Ht) as well as Ru360. Cyclosporine-A did not modify the stunning of C or CPG ischemic hearts, suggesting that the mPTP was not opened. CONCLUSIONS: Mitochondria have a precise role for determining cardioprotection or stunning in high-K+ cardioplegic rat hearts under I/R. Known protective drugs, such as Dzx and Ru360, which reduce the mitochondrial Ca2+-uptake, increased the stunning of CPG-rat hearts and reduced muscle economy, whereas 5-hydroxydecanoate and Clzp together increased the stunning by inducing mitochondrial Ca2+ overload. |
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Authors:
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María Inés Ragone; Alicia E Consolini |
Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 54 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2010-05-06 Completed Date: 2010-08-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 213-22 Citation Subset: IM |
Affiliation:
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Cátedra de Farmacología, Area Farmacia, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium Channel Agonists / pharmacology Calcium Channel Blockers / pharmacology Calcium Channels / metabolism* Cardioplegic Solutions Heart / drug effects, physiopathology* Heart Arrest, Induced Heart Rate / drug effects Mitochondria, Heart / drug effects, enzymology*, physiology* Mitochondrial Membrane Transport Proteins / antagonists & inhibitors Myocardial Reperfusion Injury / physiopathology* Myocardial Stunning / chemically induced Potassium Channel Blockers / pharmacology Potassium Channels / agonists Rats Rats, Sprague-Dawley Sodium-Calcium Exchanger / antagonists & inhibitors Time Factors Ventricular Pressure / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Agonists; 0/Calcium Channel Blockers; 0/Calcium Channels; 0/Cardioplegic Solutions; 0/Mitochondrial Membrane Transport Proteins; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Sodium-Calcium Exchanger; 0/mitochondrial calcium uniporter; 0/mitochondrial permeability transition pore |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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