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We also evaluated the effects of aprindine on experimental AF in isolated guinea-pig hearts.
Electrophysiological analyses including the envelope of tails test revealed that aprindine preferentially inhibits IKr rapidly activating component but not IKs slowly activating component. ACh with the IC50 values of 0.
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In atrial cells stimulated at 0. The drug also reversed the carbachol-induced action potential shortening in a concentration-dependent manner. In isolated hearts, perfusion of carbachol 1 μM shortened monophasic action potential MAP and effective refractory period ERPand lowered atrial fibrillation threshold. We atrial fibrillation mortality calculator the efficacy of aprindine against AF may be at least in part explained by its inhibitory effects on IKr and IK.
Therefore the insight is growing that it may not be sufficient to control the ventricular rate during AF, but it may be necessary to cure AF itself in order to prevent the serious adverse outcome.
Many investigators were devoted to the mechanisms of AF, and the wavelet hypothesis for AF has emerged from the mapping studies on experimental AF Allessie et al. It was established that several wavelets and the shortened length of wavelet, i.
Hypertonia és Nephrologia
As the wavelength is the product of refractory period and conduction velocity, the pharmacological strategy for prevention of AF is to prolong atrial refractory periods or to increase conduction velocity.
ACh are involved in the repolarization of the action potential in atrial cells Carmeliet, Class I antiarrhythmic drugs have been subdivided according to their effects on action potential duration APD : class Ia lengthens the duration, Ib shortens it, and Ic has no effects or minimally increases APD. Since aprindine hydrochloride hereafter abbreviated as aprindine was demonstrated to depress the maximum upstroke velocity of the action potential Vmax and abbreviate APD in Purkinje and ventricular tissues Verdonck et al.
However, aprindine has been shown to be effective against not only ventricular arrhythmias but also supraventricular arrhythmias including AF Kesteloot et al.
Since aprindine potently inhibited IK. ACh and the rapid component of IK IKr in this study, we also evaluated the effects of aprindine on the experimental AF in Langendorff-perfused guinea-pig hearts. Single atrial cells of the guinea-pig heart were isolated by an enzymatic dissociation method, as described previously Tohse et al.
The heart was removed from open chest guinea-pigs — g anaesthetized with pentobarbitone petrezselyem cukorbetegség kezelésében and mounted on a modified Langendorff perfusion system for retrograde perfusion of the coronary circulation with a normal HEPES-Tyrode's solution.
Atrial tissue was cut into small pieces in the modified KB solution and gently shaken to dissociate cells.
Whole-cell membrane currents were recorded by the patch-clamp method Hamill et al. The temperature of the external solution was kept constant at Patch pipettes were made from glass capillaries with a diameter of 1. They were filled with an internal solution, and their resistance was 2—4 MΩ. After the giga-ohm seal between the tip of the electrode and the cell membrane was established, the membrane patch was disrupted by more negative atrial fibrillation mortality calculator to make the whole-cell voltage-clamp mode.
Recordings were filtered at 1 kHz bandwidth, and series resistance was compensated. In addition, the envelope of tails test was performed.
GASTRO-ENTEROSTOMY WITH EXCLUSION OF INOPERABLE CANCER OF PYLORUS AND ANTRUM | JAMA | JAMA Network
The ratio of tail current of IK IK,tail to the time-dependent current activated during depolarizing pulses of various durations IK,depo was determined in the absence and presence of aprindine. The IK,tail was measured as a peak current which was actually recorded upon the clamp back atrial fibrillation mortality calculator the holding potential. The deactivation kinetics of IK was also analysed by using an exponential fitting.
The exponential analysis of IK,tail after ms and 5 s depolarizing pulses was performed by fitting the deactivation kinetics to an equation of the following form; where τ1 and τ2 are fast and slow time constants, A1 and A2 are the amplitudes of each component and A0 is the baseline value. The curve-fitting procedure used a non linear least-squares algorithm.
GASTRO-ENTEROSTOMY WITH EXCLUSION OF INOPERABLE CANCER OF PYLORUS AND ANTRUM
We used two exponentials fitting for IK,tail analysis before and after aprindine because we could obtain better least square residual values. The IK. Effects of various concentrations of aprindine on the IK. ACh activated in three different ways were examined.
To calculate per cent inhibition of IK. Current-clamp experiments were also performed in the whole-cell recording mode at 36±1°C. External and pipette solutions were the same as those used to record the carbachol-induced IK.