Gene/Protein Disease Symptom Drug Enzyme Compound
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 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model which relates the left ventricular (LV) geometry, structure and sarcomere properties to its global function, recently proposed by the authors, is extended to account for contractility changes which are a function of the heart rate, prematurity of the beat and calcium transients within the cell. To characterise LV function and relate it to fibre function under varying rhythm conditions, a model of muscle force restitution, based on calcium kinetics, was used to calculate the maximum fibre stress at the optimum sarcomere length sigma o as the parameter which depends on the heart rate, the test pulse interval TPI, the action potential duration APD and the restitution time constant. The global LV force interval relationship FIR was then calculated, and by comparing the calculated FIR to the experimental measurement (in dogs) at the ventricular level, the constants of the restitution of force at the fibre level were derived. Based on these constants, the LV function under ejecting conditions at various rhythm disturbances was calculated and related to the local, distributed parameters. This approach provides a tool to describe ventricular function as well as transmural distribution of stress and sarcomere length at a wide variety of loading and rhythm conditions based on given 'muscle level' parameters.
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PMID:Force interval relationship (FIR) related to the global function of the left ventricle: a computer study. 227 45

The intracellular electrophysiological properties of a new, orally effective antiarrhythmic agent, indecainide hydrochloride, were studied in isolated canine myocardial preparations stimulated at 1 Hz and superfused with Tyrode's solution. In Purkinje fibers, indecainide (10(-6) and 3 X 10(-6) M) decreased the maximal rate of rise of phase 0 (Vmax), conduction velocity, action potential duration APD, and effective refractory period, and shifted the membrane response curve by 5 mV in a hyperpolarizing direction. In papillary muscle, APD was unchanged, but Vmax was decreased. The effect of the drug on Vmax was rate dependent, but over physiologically relevant cycle lengths (370 to 1,000 ms), Vmax remained relatively constant. In the presence of indecainide (3 X 10(-6) M) and at a basic cycle length of 333 ms, the rate constant for block onset was 0.06 and 0.1 action potentials-1 in Purkinje fiber and papillary muscle, respectively. The recovery of Vmax from maximum steady-state block was half completed in Purkinje fibers and muscle in 52 and 49 s, respectively. No resting block was apparent in either tissue at normal resting membrane potential. Indecainide had only minimal effects on automaticity arising from normal or depolarized (barium) membrane potentials. Thus, indecainide is a potent class I local anesthetic antiarrhythmic agent that depresses Vmax and conduction in cardiac tissues. The depressant effects of indecainide are completely dependent on prior activation of the tissue, but because of its slow kinetics for recovery from sodium channel block, little additional change in Vmax occurs within physiologically relevant heart rates and prematurity intervals.
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PMID:Electrophysiological studies of indecainide hydrochloride, a new antiarrhythmic agent, in canine cardiac tissues. 620 15