Abstract:
OBJECTIVE:We investigate the impact of different regimens of parenteral hydrogen sulfide (H2S) administration on myocardium during ischemia-reperfusion (IR) and the molecular pathways involved in its cytoprotective effects. METHODS:Eighteen male Yorkshire pigs underwent 60 minutes of mid-left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. Pigs received either placebo (control, n = 6) or H2S as a bolus (bolus group, n = 6, 0.2 mg/kg over 10 seconds at the start of reperfusion) or as an infusion (infusion group, n = 6, 2 mg.kg.h initiated at the onset of ischemia and continued into the reperfusion period). Myocardial function was monitored throughout the experiment. The area at risk and myocardial necrosis was determined by Monastral blue/triphenyl tetrazolium chloride staining. Apoptosis and the expression pattern of various intracellular effector pathways were investigated in the ischemic territory. Coronary microvascular reactivity to endothelium-dependent and endothelium-independent factors was measured. RESULTS:H2S infusion but not bolus administration markedly reduce myocardial infarct size (P < 0.05) and improve regional left ventricular function, as well as endothelium-dependent and endothelium-independent microvascular reactivity (P < 0.05). The expression of B-cell lymphoma 2 (P = 0.059), heat shock protein 27 and alphaB-crystallin (P < 0.05) were lower in H2S-treated groups. Infusion of H2S caused higher expression of phospho-glycogen synthase kinase-3 beta isoform(P < 0.05) and lower expression of mammalian target of rapamycin and apoptosis-inducing factor (P < 0.05). Bolus of H2S caused higher expression of phospho-p44/42 MAPK extracellular signal-regulated kinase and lower expression of Beclin-1 (P < 0.05). The expression of caspase 3 and cleaved caspase 3 were lower (P < 0.05), whereas the expression of phospho-Bad(Ser136) was higher in the bolus group versus control and infusion groups (P < 0.05). The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cell count was lower in both H2S-treated groups compared with the control (P < 0.05). CONCLUSIONS:This study demonstrates that infusion of H2S is superior to a bolus alone in reducing myocardial necrosis after IR injury, even though some markers of apoptosis and autophagy were affected in both H2S-treated groups. Thus, the current results indicate that infusion of H2S throughout IR may offer better myocardial protection from IR injury.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Osipov RM,Robich MP,Feng J,Liu Y,Clements RT,Glazer HP,Sodha NR,Szabo C,Bianchi C,Sellke FWdoi
10.1097/FJC.0b013e3181b2b72bsubject
Has Abstractpub_date
2009-10-01 00:00:00pages
287-97issue
4eissn
0160-2446issn
1533-4023journal_volume
54pub_type
杂志文章abstract::Both population (mass) strategies and targeted strategies for the management of high blood pressure are necessary. However, it has yet to be proven that reducing blood pressure by lifestyle changes in the population will confer the same cardiovascular benefit that results from lowering blood pressure by drugs. It is i...
journal_title:Journal of cardiovascular pharmacology
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abstract::In congestive heart failure, the chronic sympathetic hyperactivity contributes to a poor prognosis. In this respect, clonidine, a centrally acting sympathoinhibitory drug, has previously been tested in clinical trials. The aim of the current study was to evaluate the effects of clonidine on morbidity and mortality in ...
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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abstract::In conscious rats, intrathecal (i.t.) administration of norepinephrine (NE) produced pressor responses, whereas i.t. epinephrine (Epi) caused depressor responses at low doses (0.1-1 microgram) and pressor responses at a higher dose (10 micrograms). Epi administered i.t. produced bradycardia; however, NE caused tachyca...
journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-199209000-00005
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abstract::Forty patients (aged 28-66 years) with essential hypertension were randomized to 14 weeks of treatment with diltiazem or hydrochlorothiazide (HCTZ) in a double-blind, parallel study design. A significant reduction in supine body weight (-6.0 +/- 1.5 lb; p less than 0.001) and increase in pulse (+6 +/- 2 beats/min; p l...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of cardiovascular pharmacology
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abstract::Trimetazidine has no hemodynamic/antithrombotic actions. Hence, its anti-ischemic properties have been mostly attributed to its metabolic effects. However, this issue is not completely elucidated. We investigated whether inhibition of neutrophil activation may also contribute to its cardioprotective action. We first s...
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-199404000-00002
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1995-01-01 00:00:00
abstract::The effects of 3 quinazoline alpha-adrenoreceptor antagonists, prazosin, trimazosin, and UK-33,274, on lying blood pressure (BP), BP response to 60 degrees tilt, pressor response to noradrenaline, phenylephrine, and exercise (isometric and dynamic) were measured in a double-blind study in 6 volunteers. There was no di...
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1995-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2008-12-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199409000-00012
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND:Dopamine is an inotrope effective in the short term treatment of acute heart failure - including that caused by coronary artery disease. Catecholamines however can potentiate platelet activation and pre-dispose to coronary thrombosis. AIMS:Dopamine was studied for effect on agonist induced human platelet Ca...
journal_title:Journal of cardiovascular pharmacology
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更新日期:2009-03-01 00:00:00