Cardiac electrophysiologic and antiarrhythmic actions of a pavine alkaloid derivative, O‐methyl‐neocaryachine, in rat heart

Abstract

1 O-methyl-neocaryachine (OMNC) suppressed the ischaemia/reperfusion-induced ventricular arrhythmias in Langendor-perfused rat hearts (EC 50 =4.3 mM). Its electrophysiological eects on cardiac myocytes and the conduction system in isolated hearts as well as the electromechanical eects on the papillary muscles were examined. 2 In rat papillary muscles, OMNC prolonged the action potential duration (APD) and decreased the maximal rate of depolarization (V max ). As compared to quinidine, OMNC exerted less eects on both the V max and APD but a positive inotropic eect. 3 In the voltage clamp study, OMNC decreased Na + current (I Na ) (IC 50 =0.9 mM) with a negativeshift of the voltage-dependent inactivation and a slowed rate of recovery from inactivation. The voltage dependence of I Na activation was, however, unaected. With repetitive depolarizations, OMNC blocked I Na frequency-dependently. OMNC blocked I Ca with an IC 50 of 6.6 mM and a maximum inhibition of 40.7%. 4 OMNC inhibited the transient outward K + current (I to ) (IC 50 =9.5 mM) with an acceleration of its rate of inactivation and a slowed rate of recovery from inactivation. However, it produced little change in the steady-state inactivation curve. The steady-state outward K + current (I SS ) was inhibited with an IC 50 of 8.7 mM. The inward recti®er K + current (I K1 ) was also reduced by OMNC. 5 In the perfused heart model, OMNC (3 to 30 mM) prolonged the ventricular repolarization time, the spontaneous cycle length and the atrial and ventricular refractory period. The conduction through the AV node and His-Purkinje system, as well as the AV nodal refractory period and Wenckebach cycle length were also prolonged (30 mM). 6 In conclusion, OMNC blocks Na + , I to and I SS channels and in similar concentrations partly blocks Ca 2+ channels. These eects lead to a modi®cation of the electromechanical function and may likely contribute to the termination of ventricular arrhythmias. These results provide an opportunity to develop an eective antiarrhythmic agent with modest positive inotropy as well as low proarrhythmic potential.

Cardiac Electrophysiological and Antiarrhythmic Effects of <i>N</i>-n-butyl Haloperidol Iodide

“…After a further 5 min of perfusion, the left anterior descending coronary artery was ligated for 20 min before the release of the ligature. The establishment of ischaemia/reperfusion was ascertained by the amount of coronary effluent [9]. Successful occlusion was confirmed by 30% -40% reduction in coronary flow as compared with pre-ischaemic values.…”

“…At this constant rate pacing, the intra-atrial conduction time (SA), atrioventricular nodal conduction time (AH), His-Purkinje conduction time (HV) and ventricular repolarization time (VRT) were measured. The 3 following stimulating protocols were introduced for electrophysiological studies [9]. (1) Incremental right atrial pacing was used to determine the Wenckebach cycle length (WCL).…”

Multiple Cellular Electrophysiological Effects of a Novel Antiarrhythmic Furoquinoline Derivative HA-7 [N-Benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione] in Guinea Pig Cardiac Preparations

“…and given heparin (300 units/kg, i.p.). Following anesthesia, the heart was excised via thoracotomy and the ascending aorta was retrogradely perfused at a rate of 4 ml/min/g cardiac tissue with normal Tyrode's solution (Chang et al, 2002). The solution was continuously gassed with 95% O 2 and 5% CO 2 to give a pH of 7.4 and was maintained at 37°C.…”

“…Action potentials were recorded from guinea pig cardiac muscle preparations with a conventional intracellular recording technique (Chang et al, 2002). In brief, the left atrial strip or ventricular papillary muscle was placed in a tissue chamber and perfused at a rate of 20 ml/min with normal Tyrode's solution.…”

Effects of anandamide on potassium channels in rat ventricular myocytes: a suppression of Ito and augmentation of KATP channels

“…Isolation of ventricular myocytes. Cardiac ventricular myocytes were isolated by using enzymatic dissociation, as described previously (5). Briefly, the rat was anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg) and heparin (300 U/kg).…”