Voltage-sensitive dye mapping in Langendorff-perfused rat hearts.
ABSTRACT An imaging system suitable for recordings from Langendorff-perfused rat hearts using the voltage-sensitive dye 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) has been developed. Conduction velocity was measured under hyper- and hypokalemic conditions, as well as at physiological and reduced temperature. Elevation of extracellular [K(+)] to 9 mM from 5.9 mM caused a slowing of conduction velocity from 0.66 +/- 0.08 to 0.43 +/- 0.07 mm/ms (35%), and reduction of the temperature to 32 degrees C from 37 degrees C caused a slowing from 0.64 +/- 0.07 to 0.46 +/- 0.05 mm/ms (28%). Ventricular activation patterns in sinus rhythm showed areas of early activation (breakthrough) in both the right and left ventricle, with breakthrough at a site near the apex of the right ventricle usually occurring first. The effects of mechanically immobilizing the preparation to reduce motion artifact were also characterized. Activation patterns in epicardially paced rhythm were insensitive to this procedure over the range of applied force tested. In sinus rhythm, however, a relatively large immobilizing force caused prolonged PQ intervals as well as altered ventricular activation patterns. The time-dependent effects of the dye on the rat heart were characterized and include 1) a transient vasodilation at the onset of dye perfusion and 2) a long-lasting prolongation of the PQ interval of the electrocardiogram, frequently resulting in brief episodes of atrioventricular block.
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ABSTRACT: Two animal models - guinea pig and rabbit - were used to record monophasic action potentials using voltage sensitive dye di-4-ANEPPS in isolated hearts perfused according to Langendorf. The hearts undergo the same isolation and loading procedures. Changes in electrogram and coronary flow are followed. During the loading and washout, prominent electrophysiological changes occur (mainly decrease of spontaneous heart rate and changes in the shape of T wave), accompanied with decrease in mean coronary flow. However, these changes differ in the two species. It may be concluded that rabbit heart is more resistant to the changes which are triggered with VSD application. Although these changes are partially reversible in guinea pig heart, this model seems to be more sensitive and thus less reliableComputers in Cardiology, 2005; 02/2005
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ABSTRACT: In normal cardiac function, orderly activation of the heart is facilitated by the Purkinje system (PS), a specialized network of fast-conducting fibers that lines the ventricles. Its role during ventricular defibrillation remains unelucidated. Physical characteristics of the PS make it a poor candidate for direct electrical observation using contemporary experimental techniques. This study uses a computer modeling approach to assess contributions by the PS to the response to electrical stimulation. Normal sinus rhythm was simulated and epicardial breakthrough sites were distributed in a manner consistent with experimental results. Defibrillation shocks of several strengths and orientations were applied to quiescent ventricles, with and without PS, and electrical activation was analyzed. All shocks induced local polarizations in PS branches parallel to the field, which led to the rapid spread of excitation through the network. This produced early activations at myocardial sites where tissue was unexcited by the shock and coupled to the PS. Shocks along the apico-basal axis of the heart resulted in a significant abbreviation of activation time when the PS was present; these shocks are of particular interest because the fields generated by internal cardioverter defibrillators tend to have a strong component in the same direction. The extent of PS-induced changes, both temporal and spatial, was constrained by the amount of shock-activated myocardium. Increasing field strength decreased the transmission delay between PS and ventricular tissue at Purkinje-myocardial junctions (PMJs), but this did not have a major effect on the organ-level response. Weaker shocks directly affect a smaller volume of myocardial tissue but easily excite the PS, which makes the PS contribution to far field excitation more substantial than for stronger shocks.Annals of Biomedical Engineering 10/2009; 38(2):456-68. · 3.23 Impact Factor
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ABSTRACT: Dofetilide (DOF), a novel Class III antiarrhythmic drug, prolongs the action potential duration (APD) and shows a positive inotropic effect in guinea pig papillary muscle. The present experiments were designed to study the positive inotropic effect of DOF on rat ventricle and explore its possible mechanism(s). Hearts from male Wistar rats (260-320 g) were divided into five groups and perfused in Langendorff mode. Ventricular myocytes were enzymatically isolated from male Wistar rats. Whole-cell voltage-clamping technique was used to test the Na(+)-Ca(2+) exchange (NCE) current (I(NCX)); Calcium transients and cell shortening provoked by field stimulation or using calcium current command waveform were observed synchronously with an ionic imaging system. DOF (0.03-1.0 microM) increased left ventricular function in isolated rat hearts in a concentration-dependent manner. DOF (0.03-1.0 microM) also concentration-dependently increased both inward and outward I (NCX) in isolated rat ventricular cells. The EC(50) values of DOF were 0.149 microM for the inward I(NCX) and 0.249 microM for outward I(NCX), respectively. DOF 0.2 microM significantly enhanced Ca(2+) transient and cell shortening in single rat ventricular myocytes driven by field electric stimulation. When the patch clamp system was connected to the ionic imaging system, Ca(2+) current (I(Ca)), Ca(2+) transient and cell shortening amplitude in a same cell were recorded synchronously. Application of DOF 0.2 microM had no effect on I(Ca), but significantly increased Ca(2+) transient and cell shortening. NCX inhibitor KB-R7943 0.6 microM significantly depressed the effects of DOF on Ca(2+) transient and cell shortening. We conclude that DOF enhanced contractility of rat ventricular myocytes. The enhancement of NCE may be involved in the positive inotropic action of DOF.Cardiovascular Drugs and Therapy 03/2009; 23(3):207-14. · 2.67 Impact Factor