Hitoshi Adaniya

Effects of magnesium on polymorphic ventricular tachycardias induced by aconitine.

We examined the effects of Mg2+ on aconitine-induced polymorphic ventricular tachycardias (PVT) in excised rabbit hearts under Langendorff perfusion and in Purkinje-muscle preparations. Local electrograms using bipolar electrodes and transmembrane potentials with the microelectrode technique were recorded from Langendorff hearts and Purkinje-muscle preparations, respectively. In Langendorff preparations, intracoronary application of 0.1 microM aconitine induced PVT 28.8 +/- 3.4 min after development of regular monomorphic ventricular tachycardias (MVT) in all 18 preparations. Application of 5 and 10 mM Mg2+ restored aconitine-induced PVT to sinus rhythm after 26.8 +/- 3.4 min (n = 9), but < 3 mM Mg2+ was not effective in restoring of sinus rhythm. Increased Mg2+ concentrations < or = 5 mM in the coronary perfusate prevented development of PVT by aconitine. Intracoronary application of 10 microM tetrodotoxin (TTX) also restored aconitine-induced PVT to sinus rhythm after 3.2 +/- 0.8 min (n = 4). Although applications of 50 microM lidocaine, 10 microM flecainide, or 1 microM verapamil could change PVT to MVT, they were not effective in restoring sinus rhythm. In Purkinje-muscle preparations, spontaneous action potentials (AP) from slow diastolic depolarization appeared after aconitine at the maximum diastolic potential of -75.0 +/- 3.7 mV in Purkinje fibers and were conducted to ventricular muscles (n = 5). Spontaneous activity gradually increased in rate and then developed triggered activity arising from early after depolarization (EAD). EAD induced by aconitine always appeared first in Purkinje fibers and later in muscle fibers. Once triggered activities started from EAD, rate, rhythm and amplitudes of APs became fast and variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a novel class III antiarrhythmic agent, E-4031, on reentrant tachycardias in rabbit right atrium.

Effects of a new antiarrhythmic agent, E-4031, on reentrant types of tachycardias in rabbit right atrial preparations were studied using the microelectrode technique. E-4031 at concentrations of 0.1 and 1.0 μM prolonged the refractory period (RP) of the atrium and atrioventricular node (AVN) without affecting the intraatrial conduction time. In 13 of 17 preparations, premature stimulation repeatedly induced tachycardias lasting more than 10 beats. Twelve of 13 preparations exhibited a smooth AV conduction curve and showed activation patterns compatible with intraatrial reentry (IAR) during tachycardias, whereas the remaining preparation started tachycardia with a jump on the AV conduction curve, indicating dual AVN reentrant tachycardia (AVNRT). Application of 0.1 and 1.0 μM E-4031 completely prevented the initiation of both types of tachycardias by producing intraatrial conduction block due to prolonged effective refractory period (ERP) of the atrium. The results indicated that E-4031 exhibiting pure class III antiarrhythmic properties is effective for prevention of reentrant type of supraventricular tachycardias (SVTs).

Electrophysiological Effects of Clentiazem, a New Ca2+ Antagonist, on Rabbit Hearts

Electrophysiological effects of clentiazem, a new 1,5-benzothiazepine type Ca(2+) antagonist, were examined in comparison with those of diltiazem in excised rabbit heart preparations. In Langendorff-perfused hearts electrically driven at basic cycle lengths of 400-500 ms, clentiazem (10(-8)-10(-6)M) and diltiazem (10(-8)-10(-6)M) caused a concentration-dependent prolongation of the atrio-His bundle conduction time (A-H interval) without affecting the His bundle-ventricular conduction time (H-V interval). The effects of clentiazem were equivalent to those of diltiazem. In isolated rabbit atrioventricular (A-V) node preparations electrically driven at 400- to 500-ms intervals, clentiazem and diltiazem at >10(-6)M concentrations produced concentration-dependent decreases in action potential amplitude (APA), maximum rate of depolarization (V max), and shortened action potential duration at 20 and 50% repolarization (APD(20) and APD(50)), whereas APD(90) was little affected. Application of 10(-6)M clentiazem prolonged effective refractory period (ERP) of the A-V node by approximately 7% of the control, an effect similar to that of diltiazem. In spontaneously beating sinoatrial (S-A) node preparations, clentiazem l0(-6)M or the higher concentration significantly decreased APA, V(max), and slope of slow diastolic depolarization, while reducing the maximum diastolic potential. The inhibitory effects of clentiazem showed strong suppression of APA and V(max) by 31.1 and 47.2% of the control, respectively, whereas both clentiazem (10(-7)-10(-5)M) and diltiazem (10(-7)-10(-5)M) had no effects on parameters of ventricular APs. These results suggest that dentiazem, like diltiazem, has a preferential inhibitory action on cardiac slow Ca(2+) channels.

Electrophysiological properties of a new antiarrhythmic agent, bisaramil on guinea-pig, rabbit and canine cardiac preparations

SummaryElectrophysiological effects of bisaramil, a novel antiarrhythmic agent, were examined using the conventional microelectrode technique applied to cardiac multicellular preparations from guinea-pigs, rabbits and dogs and the whole-cell patch-clamp technique applied to guinea-pig ventricular myocytes. Bisaramil at 10−6 M or higher concentrations produced a dose-dependent decrease in the maximum rate of rise (

Function of atrial preferential conduction routes under normal and abnormal conditions

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Mechanism of Openings and Role of the ATP-Sensitive K+ Channels during Myocardial Ischemia/Reperfusion

max) of action potentials of guinea-pig papillary muscles without changes in resting membrane potentials. In the presence of bisaramil, trains of stimuli at rates > 0.1 Hz led to the use-dependent block of

Mechanisms of the rate-dependent effects of new class III agent, sematilide, on action potential duration in isolated guinea-pig ventricular myocytes.

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