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Ischemia-reperfusion injury changes the dynamics of Ca2+-contraction coupling due to inotropic drugs in isolated hearts. J Appl Physiol (1985) 2006 Mar;100(3):940-50

Date

11/12/2005

Pubmed ID

16282437

DOI

10.1152/japplphysiol.00285.2005

Scopus ID

2-s2.0-33645548811   10 Citations

Abstract

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.

Author List

Rhodes SS, Ropella KM, Camara AK, Chen Q, Riess ML, Pagel PS, Stowe DF

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin
David F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adrenergic beta-Agonists
Animals
Calcium
Cardiotonic Agents
Digoxin
Dobutamine
Dopamine
Dopamine Agonists
Feedback, Physiological
Guinea Pigs
Heart
Hydrazones
In Vitro Techniques
Myocardial Contraction
Myocardial Reperfusion Injury
Myocardium
Pyridazines
Signal Transduction
Ventricular Function, Left
jenkins-FCD Prod-409 d1e206b0be345926047b0d9c353c78a4cce4058b