1 The electrophysiological e ects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje ®bres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and patch-clamp techniques. 2 Chronic treatment with dronedarone (2625 mg 71 kg 71 day p.o. for 4 weeks), unlike chronic administration of amiodarone (50 mg 71 kg 71 day p.o. for 4 weeks), did not lengthen signi®cantly the QTc interval of the electrocardiogram or the action potential duration (APD) in papillary muscle. After chronic oral treatment with dronedarone a small, but signi®cant use-dependent V max block was noticed, while after chronic amiodarone administration a strong use-dependent V max depression was observed. 3 Acute superfusion of dronedarone (10 mM), similar to that of amiodarone (10 mM), moderately lengthened APD in papillary muscle (at 1 Hz from 239.6+5.3 to 248.6+5.3 ms, n=13, P50.05), but shortened it in Purkinje ®bres (at 1 Hz from 309.6+11.8 to 287.1+10.8 ms, n=7, P50.05). 4 Both dronedarone (10 mM) and amiodarone (10 mM) superfusion reduced the incidence of early and delayed afterdepolarizations evoked by 1 mM dofetilide and 0.2 mM strophantidine in Purkinje ®bres. 5 In patch-clamp experiments 10 mM dronedarone markedly reduced the L-type calcium current (76.5+0.7 %, n=6, P50.05) and the rapid component of the delayed recti®er potassium current (97+1.2 %, n=5, P50.05) in ventricular myocytes. 6 It is concluded that after acute administration dronedarone exhibits e ects on cardiac electrical activity similar to those of amiodarone, but it lacks the`amiodarone like' chronic electrophysiological characteristics.
In isolated spontaneously beating right ventricular strips and right atrial preparations of guinea pigs adenosine was found to exert a concentration-dependent suppressing effect on the pacemaker activity. Responsiveness to adenosine was approximately 30-fold higher in ventricular than in atrial preparations. A decrease in the rate of slow diastolic (phase 4) depolarization of Purkinje and sinoatrial nodal fibers proved to be a major determinant of the adenosine-induced alteration in pacemaker activity. It is suggested that adenosine might exert its depressant effect on ventricular automaticity via direct excitation of purine receptors located in the specialized pacemaker fibres of the ventricular tissue.
The aim of this study was to analyse the effects of eliprodil, a noncardiac drug with neuroprotective properties, on the cardiac repolarisation under in vitro circumstances, under normal conditions and after the attenuation of the ‘repolarisation reserve’ by blocking the inward rectifier potassium current (IK1) current with BaCl2. In canine right ventricular papillary muscle by applying the conventional microelectrode technique, under normal conditions, eliprodil (1 μM) produced a moderate reverse rate‐dependent prolongation of the action potential duration (7.4±1.5, 8.9±2.1 and 9.9±1.8% at cycle lengths of 300, 1000 and 5000 ms, respectively; n=9). This effect was augmented in preparations where IK1 was previously blocked by BaCl2 (10 μM). BaCl2 alone lengthened APD in a reverse frequency‐dependent manner (7.0±1.3, 14.2±1.6 and 28.1±2.1% at cycle lengths of 300, 1000 and 5000 ms, respectively; n=8). When eliprodil (1 μM) was administered to these preparations, the drug induced a marked further lengthening relative to the APD values measured after the administration of BaCl2 (12.5±1.0, 17.6±1.5 and 20.5±0.9% at cycle lengths of 300, 1000 and 5000 ms, respectively; n=8). In the normal Langendorff‐perfused rabbit heart, eliprodil (1 μM) produced a significant QTc prolongation at 1 Hz stimulation frequency (12.7±1.8%, n=9). After the attenuation of the ‘repolarisation reserve’ by the IK1 blocker BaCl2 (10 μM), the eliprodil‐evoked QTc prolongation was greatly enhanced (28.5±7.9%, n=6). In two out of six Langendorff preparations, this QTc lengthening degenerated into torsade de pointes ventricular tachycardia. Eliprodil significantly decreased the amplitude of rapid component of the delayed rectifier potassium current (IKr), but slow component (IKs), transient outward current (Ito) and IK1 were not considerably affected by the drug when measured in dog ventricular myocytes by applying the whole‐cell configuration of the patch‐clamp technique. The results indicate that eliprodil, under normal conditions, moderately lengthens cardiac repolarisation by inhibition of IKr. However, after the attenuation of the normal ‘repolarisation reserve’, this drug can induce marked QT interval prolongation, which may result in proarrhythmic action. British Journal of Pharmacology (2004) 143, 152–158. doi:
BACKGROUND: Acute and chronic treatment with amiodarone has been reported to cause different electrocardiographic changes in patients. The cellular electrophysiologic effects of chronic administration (50 mg/kg/day orally for 6 weeks) and acute superfusion (5 µM in the tissue bath) of amiodarone were therefore studied in dog cardiac ventricular muscle and Purkinje fibers using conventional microelectrode techniques. METHODS AND RESULTS: During stimulation at 1 Hz, chronic amiodarone treatment lengthened the ventricular muscle action potential duration (APD) from 227.8 +/- 6.3 ms (n = 20) to 262.3 +/- 5.2 ms (n = 21; P <.01), but shortened that of Purkinje fibers from 337.6 +/- 9.2 (n = 21) to 308.3 +/- 7.1 (n = 19; P <.05). Acute superfusion of 5 µM amiodarone in cardiac tissue obtained from chronically treated dogs did not change ventricular muscle APD but shortened Purkinje fiber AP from 309.7 +/- 13.6 ms to 281.9 +/- 11.9 ms (n = 8; P <.05). Neither the chronic nor the acute amiodarone exposure prevented the APD shortening in ventricular muscle evoked by 10 µM pinacidil, suggesting that amiodarone does not interfere with the ATP-dependent potassium channels. The normal difference in APD between ventricular muscle and Purkinje fibers in untreated, control preparations was 110 ms but decreased to 46 ms in fibers obtained from dogs chronically treated with amiodarone and increased to 185 ms in fibers obtained from dogs chronically treated with amiodarone and increased to 185 ms in the presence of 30 µM sotalol, a class III antiarrhythmic drug used for comparison. Amiodarone (5 µM) applied directly abolished early afterdepolarizations (EADs) (induced by 1 µM dofetilide + 20 µM BaCl(2) + 2 mM CsCl) in 5 of 6 experiments and caused strong use-dependent V(max) block with relatively fast onset kinetics (rate constant = 1.23 +/- 0.13 AP(-1), n = 5) and offset (time constant = 364 +/- 62.5 ms, n = 5). After chronic amiodarone treatment, in contrast with acute sotalol application (30 µM), no reverse use-dependent effect was observed on the APD in Purkinje fibers. CONCLUSIONS: These results provide further evidence that amiodarone differs from other recognized class III antiarrhythmic drugs (ie, it is a mixed type agent with acute fast kinetic class I [type B] and a unique class III antiarrhythmic action characterized by decreased dispersion of APDs between ventricular muscle and Purkinje fibers). Amiodarone can abolish EADs unlike other class III agents that are usually associated to induction of EADs. These features might be responsible not only for the antiarrhythmic efficacy, but also for the relative safety (low incidence of torsade de pointes) of amiodarone in clinical settings.
Beside steam reforming, methane pyrolysis is an alternative method for hydrogen production. ‘Turquoise’ hydrogen with solid carbon is formed in the pyrolysis process, contrary to ‘grey’ or ‘blue’ hydrogen via steam methane reforming, where waste carbon dioxide is produced. Thermal pyrolysis is conducted at higher temperatures, but catalytic decomposition of methane (CDM) is a promising route for sustainable hydrogen production. CDM is generally carried out over four types of catalyst: nickel, carbon, noble metal and iron. The applied reactors can be fixed bed, fluidized bed, plasma bed or molten-metal reactors. Two main advantages of CDM are that (i) carbon-oxide free hydrogen, ideal for fuel cell applications, is formed and (ii) the by-product can be tailored into carbon with advanced morphology (e.g., nanofibers, nanotubes). The aim of this review is to reveal the very recent research advances of the last two years achieved in the field of this promising prospective technology.
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