Linked Life Data

10773021

Source:http://linkedlifedata.com/resource/pubmed/id/10773021

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-6-21
pubmed:abstractText
The mechanisms of the inotropic effect of mitoxantrone (MTO), a synthetic dihydroxyanthracenedione derivative with antineoplastic activity, was investigated in guinea pig ventricular myocytes using whole-cell patch-clamp methods combined with fura-2 fluorescence and cell-edge tracking techniques. In right ventricular papillary muscles, 30 microM MTO increased isometric force of contraction as well as action potential duration (APD) in a time-dependent manner. The force of contraction was increased approximately 3-fold within 4 h. This positive inotropic effect was accompanied by a prolongation of time to peak force and relaxation time. In current-clamped single myocytes treated with 30 microM MTO for 30 min, an increase of cell shortening by 77% and a prolongation of APD by 19% was observed. Peak amplitude of the intracellular Ca(2+) transients was also increased by 10%. The contribution of APD prolongation to the enhancement of cell shortening induced by MTO was assessed by clamping control myocytes with action potentials of various duration. Prolongation of APD(90) (ADP measured at 90% of repolarization) by 24% led to an increase of cell shortening by 13%. When the cells were clamped by an action potential with constant APD, MTO still caused an increase of cell shortening by 59% within 30 min. No increase of the peak intracellular Ca(2+) transients, however, was observed under this condition. We conclude that both the APD prolongation and a direct interaction with the contractile proteins contributed to the positive inotropic effect of MTO.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
501-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Effects of mitoxantrone on excitation-contraction coupling in guinea pig ventricular myocytes.
pubmed:affiliation
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't