|Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A.|
|PMID: 22814384 Owner: NLM Status: MEDLINE|
|BACKGROUND: We have recently shown that postischemic administration of intralipid protects the heart against ischemia-reperfusion injury. Here we compared the cardioprotective effects of intralipid with cyclosporine-A, a potent inhibitor of the mitochondrial permeability transition pore opening.
METHODS: In vivo rat hearts or isolated Langendorff-perfused mouse hearts were subjected to ischemia followed by reperfusion with intralipid (0.5%, 1% and 2% ex-vivo, and 20% in vivo), cyclosporine-A (0.2 μM, 0.8 μM, and 1.5 μM ex- vivo and 10 mg/kg in vivo), or vehicle. The hemodynamic function, infarct size, calcium retention capacity, mitochondrial superoxide production, and phosphorylation levels of protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) were measured. The values are mean ± SEM.
RESULTS: Administration of intralipid at reperfusion significantly reduced myocardial infarct size compared with cyclosporine-A in vivo (infarct size/area at risk)%: 22.9 ± 2.5% vs. 35.2 ± 3.5%; P = 0.030, n = 7/group). Postischemic administration of intralipid at its optimal dose (1%) was more effective than cyclosporine-A (0.8 μM) in protecting the ex vivo heart against ischemia-reperfusion injury, as the rate pressure product at the end of reperfusion was significantly higher (mmHg · beats/min: 12,740 ± 675 [n = 7] vs. 9,203 ± 10,781 [n = 5], P = 0.024), and the infarct size was markedly smaller (17.3 ± 2.9 [n = 7] vs. 29.2 ± 2.7 [n = 5], P = 0.014). Intralipid was as efficient as cyclosporine-A in inhibiting the mitochondrial permeability transition pore opening (calcium retention capacity = 280 ± 8.2 vs. 260.3 ± 2.9 nmol/mg mitochondria protein in cyclosporine-A, P = 0.454, n = 6) and in reducing cardiac mitochondrial superoxide production. Unlike intralipid, which increased phosphorylation of Akt (6-fold) and GSK-3β (5-fold), cyclosporine-A had no effect on the activation of these prosurvival kinases.
CONCLUSIONS: Although intralipid inhibits the opening of the mitochondrial permeability transition pore as efficiently as cyclosporine-A, intralipid is more effective in reducing the infarct size and improving the cardiac functional recovery.
|Jingyuan Li; Andrea Iorga; Salil Sharma; Ji-Youn Youn; Rod Partow-Navid; Soban Umar; Hua Cai; Siamak Rahman; Mansoureh Eghbali|
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|Type: Comparative Study; In Vitro; Journal Article; Research Support, N.I.H., Extramural|
|Title: Anesthesiology Volume: 117 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2012 Oct|
|Created Date: 2012-09-19 Completed Date: 2012-11-23 Revised Date: 2013-12-18|
Medline Journal Info:
|Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States|
|Languages: eng Pagination: 836-46 Citation Subset: AIM; IM|
|APA/MLA Format Download EndNote Download BibTex|
Anterior Wall Myocardial Infarction / pathology
Calcium / metabolism, pharmacology
Coronary Vessels / physiology
Cyclosporine / pharmacology*
Dose-Response Relationship, Drug
Electron Spin Resonance Spectroscopy
Emulsions / pharmacology
Fat Emulsions, Intravenous / pharmacology*
Glycogen Synthase Kinase 3 / metabolism
Heart Function Tests
Immunosuppressive Agents / pharmacology*
Mice, Inbred C57BL
Mitochondria, Heart / drug effects
Myocardial Reperfusion Injury / pathology, prevention & control*
Oncogene Protein v-akt / metabolism
Phospholipids / pharmacology*
Reactive Oxygen Species / analysis, metabolism
Soybean Oil / pharmacology*
|HL077440/HL/NHLBI NIH HHS; HL088975/HL/NHLBI NIH HHS; HL089876/HL/NHLBI NIH HHS; HL089876S1/HL/NHLBI NIH HHS; HL101228/HL/NHLBI NIH HHS; R01 HL077440/HL/NHLBI NIH HHS; R01 HL088975/HL/NHLBI NIH HHS; R01 HL089876/HL/NHLBI NIH HHS; T32 GM065823/GM/NIGMS NIH HHS|
|0/Cardiotonic Agents; 0/Emulsions; 0/Fat Emulsions, Intravenous; 0/Immunosuppressive Agents; 0/Phospholipids; 0/Reactive Oxygen Species; 0/soybean oil, phospholipid emulsion; 8001-22-7/Soybean Oil; 83HN0GTJ6D/Cyclosporine; EC 220.127.116.11/Oncogene Protein v-akt; EC 18.104.22.168/glycogen synthase kinase 3 beta; EC 22.214.171.124/Glycogen Synthase Kinase 3; SY7Q814VUP/Calcium|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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