Category Archives: Cardiology

Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 7)

DISCUSSION
At a stimulation rate of 1 Hz, GE 70 decreased V max in guinea pig heart muscle preparations at the same concentration range as propafenone . Block of V max was use-and frequency-dependent, which is in agreement with results obtained with propafenone . The steady state inactivation curve was not shifted by GE 70, in contrast to reports of (R)- and (S)-propafenone , indicating an absence or much lower affinity of GE 70 to the inactivated sodium channel compared with propafenone. Reported time constant of recovery from the use-dependent block by propafenone in guinea pig papillary muscles and ventricular myocytes varies from 5.3 to 15.5 s. The time constant of recovery of V max from the use-dependent block by GE 70 in guinea pig papillary muscles of 6.6±0.6 s was similar to that for propafenone. Published data for propafenone and the presented data for GE 70 suggest similarities in use- and frequency-dependent block of V max and time course of recovery from that block, but differences in the voltage dependence of V max block.
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Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 6)

Effects on single channel current: The effect of 3 |J.mol/L GE 70 on single channel kinetics was studied in (S)-DPI 201-106 treated cell-attached patches (n=4). Figure 4 shows recordings from a typical experiment. The amplitude of the single channel current remained unchanged, while average open probability was reduced from 0.70±0.08 to 0.27±0.11 (P<0.05, n=4). The number of sweeps without activity was increased twofold by 3 |J.mol/L GE 70 from 15±5% nulls in control to 33±7% (n=4). Histograms of mean open and closed times (t) were best fitted with two exponentials. The mean open times were decreased (control: T1=3.9±0.5 ms, T2=38.3±4.7 ms; 3 |J.mol/L GE 70: T1=1.7±0.4 ms, P<0.05; T2=12.7±2.9 ms, P<0.05) and mean closed times were increased (control: T1=4.5±1.2 ms, T2=63.8±17.5 ms; 3 |J.mol/L GE 70: T1=5.5±1.6 ms, P>0.1; T2=154.7±22.3 ms, P<0.05) (Figure 5). Continue reading

Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 5)

Effects on the macroscopic sodium current: GE 70 (1, 3 and 10 |J.mol/L) was added to the bathing solution in all experiments. The drug concentration dependently decreased sodium current (peak sodium current and mean current per record) with a 50% inhibitory concentration of 2.3±0.2 |j,mol/L. The percentage reduction of the ensemble-averaged current (n=5) was almost the same at any measured holding potential (-140, -120, -110, -100, -90 and -80 mV). The membrane potential required for half-maximal steady state inactivation of the cardiac sodium channels (peak sodium current, 2 Hz) was not shifted by GE 70 (3 |j,mol/L: n=5) (Figure 2). Continue reading

Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 4)

guinea pig hearts (part 4)

RESULTS Data acquisition and analysis were controlled by pCLAMP (Axon Instruments) and ASCD (Droogmans, Laboratorium voor Fysiologie, KU Leuven, Belgium).

Statistical analysis: Quantitative results are given as arithmetic means ± SEM of n experiments. P<0.05 was considered statistically significant (Student’s t test, paired observations). Continue reading

Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 3)

guinea pig hearts (part 3)

Single channel recording: Single ventricular myocytes were enzymatically dissociated . Experiments were performed at room temperature (22±1°C). A bathing solution was used containing (in mmol/L) potassium aspartate 140, MgCl2 2, EGTA 10, ATP 2 and HEPES 10, titrated with KOH to pH 7.4. Cells were depolarized by this extracellular solution to about 0 mV. The pipette solution contained (in mmol/L) NaCl 140, HEPES 10, CsCl 10, MgCl2 2 and CaCl2 1.8, titrated with NaOH to pH 7.4. Single channel currents were measured in the cell-attached mode of the patch clamp technique . Continue reading

Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 2)

ANIMALS AND METHODS

Recording of action potentials: Guinea pigs of either sex (320 to 490 g) were killed by a blow to the neck. After excision of the heart, papillary muscles were dissected from the right ventricle. The isolated preparations were fixed in a lucite chamber (volume 1.5 mL), which was continuously superfused (1.6 to 2.1 mL/min) with a gassed (95% oxygen and 5% carbon dioxide) bathing solution of the following composition (in mmol/L): NaCl 136.9, KCl 5.4, MgCl2 1.05, NaHCO3 11.9, NaH2PO4 0.42, CaCl2 1.8, glucose 5.55; pH 7.2 to 7.4. Continue reading

Electrophysiological effects of GE 70 in isolated papillary muscle and ventricular myocytes of guinea pig hearts (part 1)

guinea pig hearts (part 1)

GE 70 (rac-1-[3-(phenylethyl)-2-benzofuryl]-2-(isopropyl-amino)-ethanol hydrochloride) is a newly synthesized antiarrhythmic compound in a series of substances structurally related to propafenone (Figure 1). Racemic propafenone is classified as a Ic antiarrhythmic agent. Besides these properties propafenone posesses a weak calcium antagonistic effect and nonselective beta-adrenoceptor blocking activity, which may be clinically relevant in humans. The (+)-(S)-enantiomer is the beta-adreno-ceptor blocking moiety of propafenone, whereas both (R)-and (S)-propafenone exert equal class I antiarrhythmic activity. Propafenone blocks sodium channels during the activated and the inactivated states. The drug provoked a flickering block in DPI-modified sodium channels.
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