| The effect of K201 on isolated working rabbit heart mechanical function during pharmacologically-induced Ca(2+) overload. | |
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MedLine Citation:
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PMID: 21658026 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background and purpose: Reduced cardiac contractility has been associated with disrupted myocardial Ca(2+) signaling. The drug K201 acts on a number of Ca(2+) handling proteins and in vivo improves cardiac contractility in a variety of animal models of myocardial dysfunction. However, it is unclear whether (i) this is dependent on the systemic effects of the drug or (ii) K201 acts to reverse the effects of Ca(2+) dysregulation regardless of the cause. Experimental approach: The effect of K201 on cardiac mechanical function was assessed in isolated adult rabbit working hearts using a ventricular pressure-volume catheter. In separate experiments, the effect of K201 was investigated in hearts following pharmacologically-induced Ca(2+) overload using elevated extracellular [Ca(2+) ] ([Ca(2+) ](o) ) and β-adrenergic stimulation. Key results: K201 led to a concentration-dependent decline in systolic function (peak pressure, dP/dt(max) and preload recruitable stroke work), lusitropy (reduced dP/dt(min) and increased end diastolic pressure) and stroke volume independent of the observed decrease in heart rate. In separate experiments, mechanical function in hearts exposed to 4.5 mmol/L [Ca(2+) ](o) and 150 nmol/L isoproterenol declined until cessation of aortic flow (in 6 out of 11 hearts). However, all hearts perfused with the addition of 1.0 µmol/L K201 maintained aortic flow and demonstrated significantly improved peak systolic pressures, dP/dt(max) and dP/dt(min) . Conclusions and Implications: K201 significantly improved mechanical function of the heart during Ca(2+) overload. This suggests that K201 can limit the detrimental effects of elevated intracellular Ca(2+) and exert beneficial effects on cardiac contractile function independent of systemic effects previously observed in vivo. |
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Authors:
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A Kelly; E B Elliott; R Matsuda; N Kaneko; G L Smith; C M Loughrey |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-9 |
Journal Detail:
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Title: British journal of pharmacology Volume: - ISSN: 1476-5381 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Institute of Cardiovascular & Medical Sciences, University of Glasgow, U.K., Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi, Japan. Utsunomiya Memorial Hospital, Japan. |
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