Tedisamil in a chronic canine model of atrial flutter.

Tedisamil inhibits several cardiac potassium channels including Ito, Ikr, and the adenosine triphosphate (ATP)-sensitive potassium channel (I(KATP)), which may be important in the initiation and maintenance of atrial arrhythmias. We herein report the efficacy of tedisamil in terminating and protecting against the reinduction of atrial flutter (AFL) in a conscious canine model. Sustained AFL (> 15 min) was induced in eight of 10 mongrel dogs by programmed atrial stimulation (PAS) 2-41 days after producing a surgical barrier to conduction in the right atrium. At the time of surgery, an epicardial electrode was attached to the right atrial appendage for pacing and recording. Normal saline, 1 ml/kg, was infused after 15 min of AFL as placebo. Tedisamil (1.0 mg/kg) was given intravenously after 30 min of sustained AFL while recording surface ECGs and atrial electrograms. Conversion to sinus rhythm was achieved in 10 of 10 trials (eight dogs) in a mean time of 20.5 s (SD, +/- 11.8 s). Tedisamil had a negative chronotropic effect lasting > or =2 h and was protective against the reinduction of AFL. In five dogs, PAS was able to induce AFL in only two of seven trials 2 h after drug infusion. The corrected QT interval (QTc) was lengthened for the first 15 min after tedisamil administration (mean, +/- 39.3 ms; p < 0.05), but thereafter returned to baseline. The QRS interval was not altered by tedisamil. Saline alone, given after 15 min of sustained AFL, converted AFL in one of 11 trials (eight dogs) but did not alter the RR interval, QTc, or QRS interval compared with values measured during AFL. No significant adverse effects of tedisamil were observed. The results indicate that tedisamil is effective in interrupting and/or preventing reinduction of canine AFL, possibly by prolonging atrial refractoriness through inhibition of one or more potassium ion repolarizing currents in atrial muscle. Further studies are required to address the exact mechanism by which tedisamil exerts its antiarrhythmic effect.     

富马酸伊布利特与盐酸普罗帕酮治疗心房颤动和扑动的疗效比较

目的：比较静脉注射富马酸伊布利特与盐酸普罗帕酮治疗持续时间〈90d的房扑／房颤的有效性及安全性。方法：本研究为前瞻性随机单盲对照研究。房扑房颤患者共40例，随机分为试验组（伊布利特组，22例，其中房扑9例，房颤13例）和对照组（普罗帕酮组，18例，其中房扑7例。房颤11例）。两组分别在持续心电、血压监护下于10min内静脉推注伊布利特1mg或普罗帕酮70mg，如给药结束10min后仍未转复为窦性心律，重复前述治疗1次。观察给药后4h内的房扑／房颤的转复率及不良反应的发生情况。结果：40例中19例在90min内转复，其中盐酸普罗帕酮组5例，转复率27．8％，富马酸伊布利特组14例，转复率63．6％，两组比较差异有统计学意义（P〈0．05）。富马酸伊布利特组22例中有1例（4．4％）发生短阵室速，2例（8．1％）发生频发室早，未行特殊处理自行消失。无严重不良反应。结论：与普罗帕酮比较。富马酸伊布利特对房扑/房颤的转复具有明显的优势。     

静脉注射伊布利特转复心房颤动或心房扑动的临床分析

目的观察伊布利特注射液转复持续时间〈90d的心房颤动（简称房颤）、心房扑动（简称房扑）的有效性及安全性。方法选择心电图确诊为房颤、房扑，心室率≥60次／min且发作在90d以内的患者共52例，随机分为普罗帕酮组和伊布利特组，每组均为26例。伊布利特组：体重≥60kg者，首次静脉推注伊布利特注射液1mg；停用药后10min仍为房颤或房扑，再次静脉推注1mg。体重〈60kg者，首次0．01mg／kg静脉推注；停用药后10min仍为房颤或房扑，再次静脉给予0．01mg／kg，中途转复则立即停用。普罗帕酮组首次70mg静脉推注普罗帕酮，如无效，10min后再给予35mg，中途转复则立即停用。结果2组均能有效降低房颤或房扑的心室率，伊布利特组房颤、房扑的转复率明显高于普罗帕酮组，差异有统计学意义（65％对比42％，P〈0．01）。2组平均转复时间相比，伊布利特组明显短于普罗帕酮组，差异有统计学意义（P〈0．01）。伊布利特组3例出现短阵室性心动过速，普罗帕酮组2例出现低血压。结论伊布利特是一种起效快，对房扑、房颤患者转复率高的新型抗心律失常药物，与普罗帕酮比较，伊布利特对房扑、房颤的转复有明显的优势。     

Effects of the new class III antiarrhythmic drug E-4031 on myocardial contractility and electrophysiological parameters.

The effects of the new class III antiarrhythmic agent E-4031 were investigated in different guinea pig cardiac preparations. In left atria, E-4031 (10(-8)-10(-5) M) prolonged the functional refractory period up to 45% and reduced the frequency of spontaneously beating right atria by 32%. In papillary muscles, E-4031 (3 x 10(-8)-3 x 10(-7) M) reversibly prolonged the action potential duration (APD70) of fast and slow APs by 68 and 51%, respectively. Vmax, resting potential, and AP amplitude (APA) were not altered. In isolated ventricular myocytes, E-4031 reversibly prolonged the APD90 from 275 ms (control) to 1,496 ms (10(-6) M), pD2 value 6.5. The current changes that underlie the AP-prolonging effect were also studied in ventricular myocytes: in concentrations up to 10(-5) M), E-4031 did not affect the Na+ or Ca2+ inward current but reduced the delayed rectifier (IK) tail current by 76% (10(-7) M). Contractility was enhanced by E-4031 in isolated atria by 20% (3 x 10(-7) M) and increased cell shortening in ventricular myocytes. Thus, the class III antiarrhythmic action of E-4031 is due to a selective reduction of outward currents.     

Effect of E-4031, a class III antiarrhythmic agent, on experimental infarct size in a canine model of myocardial ischemia-reperfusion injury.

Class III antiarrhythmic agents such as E-4031 have demonstrated efficacy in preventing and/or terminating malignant ventricular arrhythmias in experimental models. It has recently been suggested that Class III agents might possess additional antiischemic properties that may translate into a reduction in the frequency or severity of arrhythmia. The potential for the Class III antiarrhythmic agent E-4031 to limit the extent of developing myocardial infarction was assessed in a barbiturate-anesthetized canine model of ischemic-reperfusion injury. Untreated control (n = 13) and E-4031-treated animals (n = 8, 300 micrograms/kg, i.v., immediately preceding myocardial ischemia) were subjected to a 90-min period of left circumflex coronary artery occlusion followed by a 5-h period of reperfusion. The predominant hemodynamic effect displayed by E-4031 was a reduction in heart rate throughout the period of coronary artery occlusion and early reperfusion. Areas at risk of infarction, expressed as percentages of left ventricle, were equivalent in the control and E-4031 treatment groups (38.5 +/- 1.0 and 34.6 +/- 1.9%, respectively). Posterolateral myocardial infarct sizes, expressed either as percentages of risk area or of total left ventricle, were reduced slightly but not significantly in the E-4031 treatment group compared to the control group (35.2 +/- 5.6 and 45.4 +/- 3.0% of risk area, respectively; 12.7 +/- 2.4 and 17.6 +/- 1.4% of left ventricle, respectively). Regional myocardial blood flows in nonischemic and central ischemic zones of myocardium did not differ significantly between the control and E-4031 treatment groups before and during the period of coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

三磷酸腺苷及双异丙吡胺防治家兔心房纤颤

实验结果表明：静脉注射三磷酸腺苷（１ｍｇ·ｋｇ－１）和双异丙吡胺（２．５，５ｍｇ·ｋｇ－１）均能有效地防治在体家兔右心房肌层注射乙酰胆碱诱发的心房纤颤。小剂量双异丙吡胺与三磷酸腺苷合用后，抗心房纤颤作用明显加强，除使ＡＦ持续时间明显缩短外，还显著降低了心房纤颤及心室纤颤发生率，动物死亡率亦明显低于单独用药组。两药单用均有抗心律失常作用及抗胆碱作用，合用后因抗胆碱作用加强而使抗心律失常效果更佳。此外，两药合用后对房室传导系统无明显不良影响。     

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 microM 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 microM 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).     

Inhibitory effect of bepridil on hKv1.5 channel current: comparison with amiodarone and E-4031

Effects of bepridil on the depolarization-activated outward K⁺ currents (I_out) in rat atrial myocytes and the human cardiac K⁺ (hKv1.5) channel current stably expressed in human embryonic kidney (HEK) 293 cells were examined, and compared with those of amiodarone and N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl] methanesulphonamide dihydrochloride dihydrate (E-4031). Membrane currents were recorded using patch-clamp techniques in enzymatically isolated rat atrial myocytes and HEK 293 cells expressing hKv1.5 channels. Bepridil potently inhibited I_out elicited by depolarization pulses and prolonged the action potential in rat atrial cells. Bepridil also inhibited the hKv1.5 channel current with the IC₅₀ value of 6.6 μM. The inhibitory effects of bepridil on the currents in HEK 293 cells were voltage-dependent. Amiodarone weakly inhibited rat atrial I_out and hKv1.5 channel current. In contrast, E-4031 at a concentration of 10 μM had little influence on these currents. Thus, bepridil inhibits hKv1.5 channel current and the inhibitory effect may be useful for the treatment of atrial fibrillation.     

伊布利特联合胺碘酮治疗心房扑动/心房颤动的疗效观察

目的观察伊布利特联合胺碘酮转复心房扑动（房扑）／心房颤动（房颤）的有效性及安全性。方法选择符合条件的患者88例,按制定的入选标准与排除标准将88例患者根据是否服用胺碘酮分为对照组和试验组。对照组：单用伊布利特;试验组：口服胺碘酮后联合伊布利特。口服胺碘酮组负荷量7～15g（3～4周内达到靶剂量）。伊布利特首剂1．0mg,10min内缓慢静脉注射,如给药10min后仍未转复为窦性心律,行第2次注射,剂量仍为1．0mg,观察开始给药后4h内转复的成功率、转复过程中用药剂量、用药前后的QT间期的差异及4h内不良反应的发生情况。结果①试验组房扑转复成功率（92％）高于对照组（56％）,但差异无统计学意义（P=0．116）;而房颤转复成功率试验组（76％）与对照组（44％）差异有统计学意义（P=0．010）;试验组（80％）与对照组（47％）房扑和房颤总的转复成功率差异亦有统计学意义（P=0．003）。②在转复房扑、房颤成功的患者伊布利特使用剂量房扑[（1．1±0．4）mg]低于房颤[（1．7±0．4）mg],差异有统计学意义（P〈0．01）。③试验组与对照组使用伊布利特前QT间期（0．49±0．08）、（0．43±0．04）差异无统计学意义（P=0．760）;2组使用伊布利特后QT间期（0．52±0．06）、（0．45±0．03）,差异亦无统计学意义（P=0．150）;试验组与对照组各自在注药前后QT间期均延长,差异有统计学意义（对照组P=-0．013;试验组P〈0．01）。④试验组有2例室性心动过速（发生率为2％）。1例在推药过程中发生尖端扭转型室性心动过速（Trip）,经电复律终止,转为窦性心律、频发室性早搏,再次房颤继之再发Tdp,静脉注射2．5g硫酸镁终止;1例在转复成功5min后发生非持续单形性室性心动过速,自行终止。2组各发生2例窦性停搏,均在2-3s后自行或经胸外按压后恢复窦性心律。结论口服胺碘酮联合伊布利特转复房扑,房颤成功率高于单一用药,并可预防其复发,联合应用未增加不良事件的发生率。     

Effects of pharmacologic agents on induced atrial flutter in dogs with right atrial enlargement

The effects of selected drugs on the sustained atrial flutter induced in conscious dogs with surgically produced right atrial enlargement (TI dogs) were evaluated. This was done to better understand the electrophysiologic mechanism of the tachyarrhythmias. Agents known to cause a slowing of atrioventricular (AV) nodal conduction--verapamil, methacholine, and phenylephrine--did not significantly decrease the rate of the induced flutter, whereas beta-adrenergic stimulation with an infusion of isoproterenol increased the rate of the flutter in all trials. Propranolol and atropine had little effect on the atrial flutter rate. Agents known to increase atrial refractoriness, such as procainamide, n-acetylprocainamide, bretylium, and clofilium, all increased the cycle length of the induced flutter and, in some cases, terminated the arrhythmia. These results suggest then that the perpetuation of the sustained atrial flutter in the conscious TI dog is not due to a delayed afterdepolarization mechanism but is more likely due to reentrant excitation. Furthermore, it is unlikely that the flutter is due to reentry over a pathway involving the AV node; rather, the arrhythmia seems to be caused by reentrant excitation of the leading circle type.     

普罗帕酮和普鲁卡因胺抗犬缺血性快速室性心律失常的对比研究(英文)

目的　观察普罗帕酮对犬在体心脏缺血性快速室性心律失常的心电生理影响并与普鲁卡因胺对比 ,以探讨其抗缺血性快速室性心律失常的效果及作用机制。方法　用冠状动脉左前降支结扎并部分再灌注法造成犬急性前壁心肌梗死 ,5～ 8d后 ,辅以心室程控电刺激 (PES)技术及冠状动脉内恒定微量直流电刺激技术 ,并诱发与终止持续性室性心动过速和心室纤颤 ,制备成犬急性心肌缺血再灌注后可控性快速室性心律失常的在体心脏心电模型 ,心电图对比观察普罗帕酮及普鲁卡因胺的抗心律失常作用。结果　普罗帕酮及普鲁卡因胺均能显著地延长心肌梗死犬的心电图QTc间期 (P <0 .0 1 )及正常和缺血心肌的有效不应期 (P <0 .0 1 ) ,降低缺血心肌和左室心肌的有效不应期离散度 (P <0 .0 1 ) ,提高正常心肌和缺血心肌的舒张期兴奋阈值 (P <0 .0 1 ) ,抑制PES诱发的持续性室性心动过速和心室纤颤 (P <0 .0 1 ) ,并能预防犬急性心肌梗死后再次缺血所致的自发性室性心动过速和心室纤颤 (P <0 .0 5)。结论　①该犬在体心脏心电药理学实验模型具有较好的重复性、可靠性及临床相关性 ,是一种有价值的心电药理学实验研究模型。②普罗帕酮及普鲁卡因胺均具有抗缺血性快速室性心律失常的心电生理作用 ,是有效的抗颤药物 ,两药效果相似     

Penetration of ASM 981 in canine skin: a comparative study.

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.     

Effects of ibutilide on spontaneous and induced ventricular arrhythmias in 24-hour canine myocardial infarction: a comparative study with sotalol and encainide.

The electrophysiologic and antiarrhythmic effects of ibutilide, sotalol, and encainide were compared in dogs 24 h after myocardial infarction. Ibutilide (0.03 to 0.3 mg/kg i.v.) prevented the induction of ventricular arrhythmias in 100% of the dogs that had demonstrated inducible ventricular arrhythmias prior to treatment. This antiarrhythmic action was associated with significant increases in ventricular refractoriness and monophasic action potential duration. Sotalol (1.0 to 10.0 mg/kg i.v.) increased the ventricular refractory period and monophasic action potential duration and prevented the induction of ventricular arrhythmias in 75% of the dogs that demonstrated inducible ventricular tachyarrhythmias at baseline. Although 10 mg/kg of sotalol was required to prevent the initiation of ventricular tachycardia, this dose produced marked cardiovascular depression and hypotension in 50% of the dogs tested. Neither ibutilide nor sotalol significantly decreased the incidence of spontaneous ventricular arrhythmias. The class IC agent encainide (0.3 to 3.0 mg/kg i.v.) was successful in preventing the induction of ventricular arrhythmias in only 20% of the dogs tested. However, in contrast to ibutilide and sotalol, encainide significantly reduced spontaneous arrhythmias. Atrial and ventricular refractoriness were significantly increased only after the highest dose of encainide tested (3.0 mg/kg). Over the dose ranges studied, the relative efficacy for prevention of pacing-induced ventricular arrhythmias was ibutilide greater than sotalol much greater than encainide. For suppression of spontaneous ventricular arrhythmias, the relative efficacy was encainide much greater than ibutilide = sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dofetilide: a review of its use in atrial fibrillation and atrial flutter

Dofetilide is a 'pure' class III antiarrhythmic agent which has demonstrated efficacy in the conversion of atrial fibrillation or flutter to sinus rhythm and the maintenance of sinus rhythm. By blocking the rapid component of the cardiac delayed rectifier potassium current (I(Kr)), dofetilide prolongs the cardiac action potential duration and the effective refractory period. This is thought to increase the likelihood of a re-entrant wavefront encountering refractory tissue and terminating the arrhythmia. Preliminary findings from the EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) and SAFIRE-D (Symptomatic Atrial Fibrillation Investigation and Randomized Evaluation of Dofetilide) studies suggest that oral dofetilide is effective in the conversion of atrial fibrillation or flutter to sinus rhythm. Both studies have yet to be published in full. In SAFIRE-D, dofetilide 500microg twice daily for 3 days achieved a conversion rate of 32% compared with a 1% rate for placebo. A similar conversion rate was achieved after 3 days in EMERALD with dofetilide 500microg twice daily (29%) which was significantly greater than that achieved with sotalol 80mg twice daily (6%; p < 0.05). Oral dofetilide also appears to be effective in the maintenance of sinus rhythm. An abstract report of EMERALD participants who had been converted to sinus rhythm showed that 71% of patients who received oral dofetilide remained in sinus rhythm after 6 months (compared with 26% of placebo and 59% of sotalol recipients: both p < 0.05). Restoration of sinus rhythm using intravenous dofetilide is more likely in patients with recent-onset versus prolonged-duration arrhythmia, and in those with atrial flutter rather than atrial fibrillation. Limitations of comparative data for intravenous dofetilide are such that few conclusions can be drawn. Although generally well tolerated in clinical trials, dofetilide has proarrhythmic potential. Torsade de pointes ventricular tachycardia was reported in up to 3.3% of patients who received oral dofetilide in the DIAMOND (Diamond Investigations of Arrhythmia and Mortality on Dofetilide) studies, although only a small proportion of patients in these studies had atrial fibrillation; most episodes occurred within the first 3 days. Whether the propensity of dofetilide for this life-threatening arrhythmia is similar to that of other class III antiarrhythmic agents has yet to be determined. Importantly, the long term use of oral dofetilide in patients at high risk for sudden cardiac death is not associated with an increased risk of mortality, although these DIAMOND findings cannot necessarily be extrapolated to patients with atrial fibrillation. CONCLUSIONS: Dofetilide offers an alternative to currently available antiarrhythmic agents for the pharmacological conversion of atrial fibrillation or atrial flutter to sinus rhythm and for the maintenance of sinus rhythm after cardioversion. However, further comparative data are necessary before its definitive place can be determined.     

Oral loading with propafenone for conversion of recent-onset atrial fibrillation: a review on in-hospital treatment

Atrial fibrillation (AF) is a very common arrhythmia. In order to treat acute AF rapidly, effective drug regimens are required. Propafenone is a class IC antiarrhythmic agent that is suitable for oral loading as it reaches peak plasma concentrations within 2 to 4 hours of administration. The use of propafenone loading in patients with AF must be based on appropriate patient selection in view of the negative inotropic effect and the potential proarrhythmic effects of the drug. A series of controlled trials in patients with recent-onset AF without heart failure who were hospitalised with enforced bed rest has shown that orally loaded propafenone (450 to 600 mg as single dose) exerts a relatively quick effect (within 3 to 4 hours) and a high rate of efficacy (72 to 78% within 8 hours). A potentially harmful effect of class IC agents is the risk of transforming AF into atrial flutter (3.5 to 5% of patients). However, atrial flutter with 1 : 1 atrioventricular response was observed in only two of 709 patients receiving propafenone (0.3% incidence). Nevertheless, the potential negative inotropic effect of propafenone demands careful patient selection, with systematic exclusion of patients with left ventricular dysfunction or congestive heart failure. Oral loading with propafenone can be considered as an episodic treatment in patients with AF recurrences, as has been proposed for other drugs in the past. However, the safety of oral loading with propafenone as an outpatient treatment in appropriately selected patients has to be assessed by appropriately designed prospective studies.     

Effects of WAY-123,398, a new class III antiarrhythmic agent, on cardiac refractoriness and ventricular fibrillation threshold in anesthetized dogs: a comparison with UK-68798, E-4031, and dl-sotalol.

Previous studies in isolated ventricular myocytes showed that WAY-123,398 is a selective blocker of the delayed rectifier K+ current (IK). In this report, we studied the electrophysiological and hemodynamic effects of WAY-123,398 in open-chest anesthetized dogs. WAY-123,398 prolonged atrial and ventricular refractoriness without affecting conduction; WAY-123,398 was as effective as UK-68798, E-4031, and dl-sotalol, but less potent than UK-68798 and E-4031. The increase in atrial refractoriness was approximately twice as large as the ventricular increase with all compounds. The hemodynamic effects of WAY-123,398 were similar to those of UK-68798; at the ED20 for increasing ventricular refractoriness, WAY-123,398 did not affect the mean arterial pressure and decreased the heart rate by 20%. In a different series of experiments, all four compounds produced large and comparable increases in the ventricular fibrillation threshold in anesthetized dogs; WAY-123,398 and UK-68798 induced defibrillation and restoration of sinus rhythm in two of six dogs each and E-4031 in one of six dogs. No episodes of drug-induced restoration to sinus rhythm were observed in dogs treated with sotalol or vehicle. In conclusion, WAY-123,398 is an effective Class III agent without Class I actions and with a favorable hemodynamic profile.     

Effects of N-acetylprocainamide and recainam in the pharmacologic conversion and suppression of experimental canine atrial flutter: significance of changes in refractoriness and conduction

The electrophysiologic determinants of the pharmacologic conversion and the prevention of atrial flutter are poorly defined. This study investigated the effects of pharmacologically induced changes in atrial conduction velocity and refractoriness, in the conversion and suppression of atrial flutter induced in the open-chest anesthetized dog by intercaval crush and rapid atrial pacing. The effects of an intravenous infusion of the new class III antiarrhythmic drug N-acetylprocainamide (30 mg/kg over 15 min) and the class Ic antiarrhythmic drug recainam (10 mg/kg over 20 min followed by 10 mg/kg/h) were evaluated. N-acetylprocainamide restored sinus rhythm in 10 of 15 (66%) dogs, while recainam converted only 2 of 10 (20%). N-acetylprocainamide prevented reinduction in 3 (20%), while recainam was effective in none. In the atria, N-acetylprocainamide induced significant increases in effective refractory period (+27%, p less than 0.01), functional refractory period (+22%, p less than 0.01), and in atrial flutter cycle length (+13%, p less than 0.01). Recainam increased effective refractory period (+28%, p less than 0.01), functional refractory period (+20%, p less than 0.01), conduction time at atrial paced cycle length of 150 msec (+70%, p less than 0.01) and atrial flutter cycle length (+56%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of CM7857, a derivative of disopyramide, on electrophysiologic properties of canine Purkinje fibers and inotropic properties of canine ventricular muscle

Effects of CM7857 on electrophysiologic properties in canine Purkinje fibers and inotropic effects in canine ventricular muscle were studied. As CM7857 is a derivative of disopyramide phosphate, the effects of CM7857 (5 mg/L, 1.5 X 10(-5) M) were compared with those of disopyramide phosphate (5 mg/L, 1.4 X 10(-5) M). CM7857 significantly lowered the maximum rate of rise of phase 0 (Vmax) from 351.5 +/- 50.6 V/s (mean +/- SE, n = 5) to 283.6 +/- 33.0 V/s, and conduction velocity from 2.68 +/- 0.56 m/s to 1.70 +/- 0.28 m/s. The automaticity of Purkinje fibers was depressed by CM7857 as the result of reduction in the slope of phase 4. These effects were comparable to those of disopyramide. A marked difference between CM7857 and disopyramide was observed in the effect on action potential duration. APD90 was significantly shortened from 327.4 +/- 14.8 ms (n = 8) to 279.9 +/- 12.9 ms by CM7857, whereas disopyramide did not show any significant changes in APD90. As the CM7857-induced shortening of APD disappeared in low [Na+]o or low [K+]o concentration, it may be attributed to the lowering effect of "window current," a steady-state sodium current, maintaining action potential plateau. Effective refractory period (ERP) did not show any significant change. An acetylstrophanthidin-induced oscillatory afterpotential was significantly depressed by disopyramide, but not by CM7857. Isotonic contraction and isometric contraction of the right ventricular trabecullae were depressed by both drugs.     

胺碘酮与普罗帕酮治疗阵发性心房颤动的疗效研究

目的对比研究静脉推注胺碘酮与普罗帕酮转复阵发性心房颤动的效果。方法122例房颤持续时间<48h的患者随机分为两组,胺碘酮组62例:胺碘酮5mg/kg10min内静脉推注;普罗帕酮组60例:普罗帕酮70mg静脉推注,5～10min注完。观察30min若未转复可重复应用。结果转复率:胺碘酮组69·4%(43/62),普罗帕酮组60%(36/60),两组转复率比较差异无统计学意义(P>0·05)。结论胺碘酮和普罗帕酮对阵发性房颤均有较高的转复率。