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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-9
pubmed:abstractText
Positive inotropic drugs may attenuate or exacerbate the deleterious effects of ischemia and reperfusion (IR) injury on excitation-contraction coupling in hearts. We 1) quantified the phase-space relationship between simultaneously measured myoplasmic Ca2+ concentration ([Ca2+]) and isovolumetric left ventricular pressure (LVP) using indexes of loop area, orientation, and position; and 2) quantified cooperativity by linearly modeling the phase-space relationship between [Ca2+] and rate of LVP development in intact hearts during administration of positive inotropic drugs before and after global IR injury. Unpaced, isolated guinea pig hearts were perfused at a constant pressure with Krebs-Ringer solution (37 degrees C, 1.25 mM CaCl2). [Ca2+] was measured ratiometrically by indo 1 fluorescence by using a fiber-optic probe placed at the left ventricular free wall. LVP was measured by using a saline-filled latex balloon and transducer. Drugs were infused for 2 min, 30 min before, and for 2 min, 30 min after 30-min global ischemia. IR injury worsened Ca2+-contraction coupling, as seen from decreased orientation and repositioning of the loop rightward and downward and reduced cooperativity of contraction and relaxation with or without drugs. Dobutamine (4 microM) worsened, whereas dopamine (8 microM) improved Ca2+-contraction coupling before and after IR injury. Dobutamine and dopamine improved cooperativity of contraction and relaxation after IR injury, whereas only dopamine increased cooperativity of relaxation before IR injury. Digoxin (1 microM) improved Ca2+-contraction coupling and cooperativity of contraction after but not before ischemia. Levosimendan (1 microM) did not alter Ca2+-contraction coupling or cooperativity, despite producing concomitant increases in contractility, relaxation, and Ca2+ flux before and after ischemia. Dynamic indexes based on LVP-[Ca2+] diagrams (area, shape, position) can be used to identify and measure alterations in Ca2+-contraction coupling during administration of positive inotropic drugs in isolated hearts before and after IR injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
8750-7587
pubmed:author
pubmed:issnType
Print
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
940-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16282437-Adrenergic beta-Agonists, pubmed-meshheading:16282437-Animals, pubmed-meshheading:16282437-Calcium, pubmed-meshheading:16282437-Cardiotonic Agents, pubmed-meshheading:16282437-Digoxin, pubmed-meshheading:16282437-Dobutamine, pubmed-meshheading:16282437-Dopamine, pubmed-meshheading:16282437-Dopamine Agonists, pubmed-meshheading:16282437-Feedback, Physiological, pubmed-meshheading:16282437-Guinea Pigs, pubmed-meshheading:16282437-Heart, pubmed-meshheading:16282437-Hydrazones, pubmed-meshheading:16282437-Myocardial Contraction, pubmed-meshheading:16282437-Myocardial Reperfusion Injury, pubmed-meshheading:16282437-Myocardium, pubmed-meshheading:16282437-Pyridazines, pubmed-meshheading:16282437-Signal Transduction, pubmed-meshheading:16282437-Ventricular Function, Left
pubmed:year
2006
pubmed:articleTitle
Ischemia-reperfusion injury changes the dynamics of Ca2+-contraction coupling due to inotropic drugs in isolated hearts.
pubmed:affiliation
Department of Anesthesiology, M4280, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. srhodes@mcw.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural