Relationship between the positive inotropic effect of ouabain and its inhibitory effects on Na+, K+ -ATPase and active transport of Rb+ in the dog heart

Two previous reports have indicated that in the dog if sustained positive inotropy without arrhythmias is induced by ouabain infusion, inhibition of myocardial Na+, K+-activated adenosine triphosphatase is not observed. Another previous study has shown that in similar experiments induction of sustained inotropy is accompanied by inhibition of the active uptake of Rb+. To resolve the apparent inconsistencies between these findings, we repeated the experiments and measured the inhibition of the enzyme and the inhibition of Rb+ uptake after the induction of sustained inotropy with ouabain. Utilizing three different ouabain dosage regimens in open-chested dogs, we obtained three different quasi-steady state plasma levels of ouabain. At the highest level, ouabain toxicity accompanied by enzyme inhibition and inhibition to RB+ uptake was observed. With the intermediate levels, positive inotropy without significant toxicity was also accompanied by enzyme inhibition and the inhibition of Rb+ uptake. At the lowest ouabain plasma levels, sustained positive inotropy without significant inhibition of either enzyme activity or +b+ uptake was obtained. The data indicate that in this preparation either a small degree of enzyme inhibition, which is difficult to detect is sufficient to produce pronounced positive inotropy, or that the inhibition of the enzyme is not required for the induction of positive inotropy.     

室性心动过速患者心率减速力与心率变异性的分析

目的测定心率减速力与心率变异性指标,分析发生室性心动过速的冠心病患者自主神经功能变化。方法选择61例冠心病患者,其中VT组31例,非VT组30例,与年龄、性别相匹配的30例正常对照组进行比较,采集24 h动态心电图的DC值、HRV各指标值进行统计分析。结果 3组间DC值、SDNN、rMSSD和pNN50比较,差异具有统计学意义(P<0.05);VT组和非VT组DC值低于对照组,VT组SDNN、rMSSD和pNN50低于对照组(P<0.05)。结论发生室性心动过速的冠心病患者自主神经功能降低,迷走神经张力降低更明显。     

The effect of theophylline alone and in combination with ouabain on the isolated dog heart

Summary A comparative study of the inotropic effects of theophylline and ouabain as well as a study of the interaction between the two pharmacological agents were carried out in the nonfailing Starling heart-lung preparation modified to permit metabolic studies. Single doses of theophylline ranging between 100 to 200 mg added to the venous reservoir produced consistent increases in myocardial contractile force, as gauged by the maximal rate of rise of left ventricular pressure, dp/dt, 73%; systemic output, 28%; coronary output, 277%; total cardiac output, 41%; heart rate, 27%; left ventricular work, 45% and myocardial oxygen consumption, 43%. In addition, systolic time decreased consistently by 15%. 20 min and 30 min after the onset of an ouabain infusion of 5g per min, which was started 15 min after the addition of theophylline, there was further increase in dp/dt to 87% and 107%, respectively, with no significant change in the remaining parameters from the levels attained 15 min after the administration of theophylline. As compared to ouabain administered alone, ouabain administered at peak effect of theophylline led to an earlier occurence of ventricular arrhythmias and death. It may be concluded from this study that maximally effective doses of theophylline brought about an increase in dp/dt which is greater than that brought about by maximal therapeutic doses of ouabain. Secondly, ouabain administered after the peak effect of theophylline was exerted led to an additional increase in dp/dt implying that the mechanisms underlying the inotropic action of each drug are different. Thirdly, at constant aortic pressure, heart rate, left ventricular enddiastolic and left atrial pressures, ouabain in the presence of theophylline brought about an increase in myocardial contractility, as gauged by an increase in dp/dt, without a concomitant increase in myocardial oxygen consumption, thus confirming earlier results obtained with ouabain alone. Fourthly, ouabain administered at peak effect of theophylline led to an earlier occurrence of ventricular arrhythmias and death.This work was supported by a grant from the Lebanese National Research Council.     

Deleterious effects of taurine in cats with digitalis-induced arrhythmias.

An established model of digitalis toxicity was used to investigate the antiarrhythmic properties of taurine. I.v. doses of taurine ranging from 0.01 to 4.0 mmole/kg were ineffective in converting a deslanoside-induced arrhythmia to sinus rhythm. Indeed, taurine was found to aggravate the arrhythmia and in three experiments precipitated ventricular fibrillation. In addition, pretreatment with 5 mmole/kg taurine i.v. had no significant effect on the doses of deslanoside to produce ventricular arrhythmia and fibrillation.     

Antiarrhythmic, electrophysiological and haemodynamic effects of prolonged oral dosing with Org 7797 in the anaesthetized rat.

The antiarrhythmic, electrophysiological and haemodynamic effects of chronic oral administration of Org 7797 ((16 alpha,17 beta)-17-methylamino-oestra-1,3,5(10)-triene-3, 16-diol-(Z)-2-butonedioate) were studied in rats. During dosing (10 mg kg-1 twice a day for 10 days) no effects on the electrocardiogram, monitored in conscious animals, were observed despite modest reductions (15-18%) in the maximum rate of depolarization of papillary muscle excised 1 or 6 h after completion of the dosing regime. Following anaesthesia, Org 7797 reduced the severity of arrhythmias induced by coronary artery occlusion and prevented the accompanying decrease in the ventricular fibrillation threshold (VFT) at 1 h after completion of dosing. By 6 h the effect on VFT had waned but protection against ischaemia-induced arrhythmias was retained despite a substantial decrease in Org 7797 plasma levels. Drug treatment did not modify arterial blood pressure, heart rate or stroke volume. We conclude that Org 7797 given chronically via the oral route exerts antiarrhythmic actions which may, at least in part, be due to sodium-channel block. In addition, our results suggest the presence of an active metabolite. The protective effects of Org 7797 were seen in the absence of electrocardiographic or haemodynamic changes suggesting that multiple oral doses of Org 7797 do not compromise normal cardiac function.     

The effect of the tricyclic antidepressant drug,nortriptyline on left ventricular ejection fraction and left ventricular volumes

Eight patients with major depression but otherwise healthy underwent radionuclide cardiography before and during nortriptyline treatment. The second examination was performed when the nortriptyline plasma concentration was within the therapeutic range (60–150 g·l^–1). Heart rate, arterial blood pressure, left ventricular ejection fraction, left ventricular volumes, systolic pressure-volume ratio, and cardiac output were determined. Heart rate increased in mean by 13% (P<0.05). All other variables were unchanged. We conclude that nortriptyline in therapeutic doses produces no major adverse effect on left ventricular function. Routine radionuclide cardiography might be a suitable method to detect among those treated with tricyclic antidepressants the occasional susceptible patient. This may particularly apply to patients with known heart disease and to elderly patients.     

Hemodynamic and myocardial effects of (-)-delta9-trans-tetrahydrocannabinol in anesthetized dogs

(?)-Δ⁹-trans-tetrahydrocannabinol (Δ⁹-THC) (39 μg–2.5 mg/kg, i.v.) decreased blood pressure, heart rate, cardiac output and right ventricular contractile force in a dose-related manner in intact dogs under pentobarbital anesthesia. The Δ⁹-THC-induced hypotension appeared to result mainly from a consistent and reproducible attenuation of cardiac output since no marked alteration in total peripheral resistance occured. In these animals the decrease in cardiac output appeared to be related to the bradycardia since there was no change in stroke volume following Δ⁹-THC. However, when the change in heart rate was prevented by atrial pacing or cardiac denervation, a less but significant reduction in cardiac output was induced by Δ⁹-THC. Under these experimental conditions Δ⁹-THC also significantly attenuated stroke volume. In contrast, Δ⁹-THC did not induce any significant changes in cardiac output, blood pressure, and heart rate of dogs pretreated with a ganglionic blocker.Δ⁹-THC appeared to be devoid of any measurable direct effect on the myocardium since the compound neither significantly altered right ventricular contractile force of the denervated or ganglionic blocker-pretreated hearts nor interfered with the positive inotropic responses to i.v. calcium and isoproterenol.In the major vessel occlusion preparation administration of Δ⁹-THC was followed by a reduction in venous tone. Furthermore, measurements of blood and plasma volume excluded an effect of Δ⁹-THC in these parameters.From these findings it is suggested that the reduction in cardiac output induced by Δ⁹-THC is the result of the action of this compound on cardiac rate as well as venous return; no evidence could be documented for a direct effect of this compound on the myocardium.     

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Abstract

Context: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations.

Objective: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat.

Materials and methods: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200?mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30?mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery.

Results: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p?<?0.05). Ventricular tachycardia (VT)/VF numbers (3.2?±?1.2), durations (4.9?±?2.6) and also arrhythmia severity (1.9?±?0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4?±?11.6, 52?±?31 and 3.3?±?0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p?<?0.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval.

Conclusion: The results suggest that pretreatment with saffron, especially at the dosage of 100?mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.     

Diuretic and hemodynamic effects of furosemide in the isolated dog kidney

Summary The effects of furosemide on the renal concentrating mechanism and on intrarenal hemodynamics were assessed in isolated blood-perfused dog kidneys. The natriuretic, diuretic and hemodynamic responses to furosemide were lesser in magnitude and shorter in duration than those seen in intact animals. Indocyanine green dye dilution curves were used to assess the intrarenal distribution of blood flow. The washout curve prior to furosemide was described by three components. After furosemide, the curve was described by four components. The greatest change in intrarenal distribution of blood flow after furosemide occurred in the noncortical compartments. The data suggest a disproportionately greater increase in medullary blood flow after furosemide. Blood flow through the slow-flow compartments increased 107% whereas flow through the fast-flow compartment increased only 7%. This is in agreement with our previous hypothesis that the increase in renal blood flow and, more importantly, the redistribution of blood flow, produced by furosemide can markedly enhance the effect of the drug, particularly on the concentrating mechanism.Work supported in part by USPHS Grant No. AM-10913 and grants from the Michigan Kidney Foundation and Hoechst Pharmaceutical Company.USPHS Predoctoral Trainee (GM-01761)     

Antiarrhythmic effects of a benzothiazine derivative (SD-3211) and its stereoisomer (SA3212) in anaesthetized rats and isolated perfused rat hearts compared with bepridil

Summary The antiarrhythmic effects of a new calcium channel blocking agent (SD-3211) and its stereoisomer with additional sodium channel blocking activity (SA3212), were compared with those of a known antiarrhythmic drug (bepridil), using the left coronary artery ligation- and reperfusion-associated arrhythmia models both in isolated rat hearts and in anaesthetized rats.Isolated and perfused rat hearts were subjected to regional ischaemia for 15 min and subsequent reperfusion for 5 min. SD-3211 and SA3212 showed dose-dependently prolongations of the time interval between coronary ligation and first appearance of ventricular premature beats, reductions in the number of total ventricular premature beats during the ligation period and reductions in the incidence of reperfusion-induced ventricular fibrillation. The values of the negative logarithm of IC₅₀ (mol/l) of SD-3211, SA3212 and bepridil were 7.97, 7.41 and 6.64 for the reduction of ventricular premature beats during ligation and 6.43, 7.49 and 6.17 for the reduction of ventricular fibrillation during reperfusion, respectively. In a separate study on force of concentration and coronary flow in perfused heart paced at 340–360 beats/min SD-3211 caused a significant negative inotropic effect between 10^–7 and 10^–6 mol/l. SA3212 at the concentration of < 10^–6 mol/l did not result in any significant change in force of contraction. The coronary flow was increased dose-dependently by SA3212, while it was first increased and then reduced in the presence of higher concentration of SD-3211 (> 10^–7 mol/l). Hearts of aneasthetized rats were also subjected to regional ischaemia for 7 min and subsequent reperfusion. SD-3211, even at the lowest dose tested (25 mg/kg), had a marked protective effect against the ligation-associated arrhythmias. The highest dosage of SA3212 tested (100 mg/kg) also reduced them. SA3212, even at the lowest dosage (25 mg/kg), resulted in a significant reduction of the incidence of reperfusion-induced ventricular fibrillation, while only the highest dosage of SD-3211 (100 mg/kg) reduced it. As for the protective effect against ligation-associated ventricular premature beats SD-3211 is about seven times as potent as bepridil, and for the reduction in the incidence of reperfusion-induced ventricular fibrillation SA3212 is about fourteen times as potent as bepridil. Significant falls in systolic blood pressure and heart rate were observed at the higher doses of SD-3211 (50 and 100 mg/kg).Thus, SD-3211 affords substantial protection against ischaemia-induced ventricular antiarrhythmias partly through the negative inotropic and chronotropic effects, and reduction of afterload. The antiarrhythmic action of SA3212 against reperfusion-induced ventricular fibrillation may be partly explained by depression of automaticity together with a reduction of the inward sodium current.Send offprint requests to M. Fukuchi at the above address     

Gabaminergic and serotonergic modulation of the antidyskinetic effects of tiapride and oxiperomide in the model using 2-(N,N-dipropyl)animo-5,6-dihydroxytetralin.

The activities of oxiperomide and tiapride were compared with those of control "neuroleptic" agents in the dyskinesia model using 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin to induce peri-oral movements, in order to determine whether the differential activities (oxiperomide and tiapride being comparatively more effective as antagonists) may involve striatal gabaminergic and serotonergic mechanisms. The peri-oral movements induced by the 2-aminotetralin compound (0.05 mg/kg s.c.) were antagonised by intrastriatal GABA (2.5--10 microgram bilateral) and serotonin (25--100 microgram bilateral). Sodium valproate (i.p.) had little effect but 1.25 mg/kg s.c. quipazine abolished the peri-oral dyskinesia. Subthreshold doses (i.p.) of oxiperomide and tiapride synergised with subthreshold intrastriatal doses of both GABA and serotonin, and with s.c. quipazine, to antagonise the peri-oral movements induced by the 2-aminotetralin compound. Subthreshold doses of haloperidol, sultopride, metoclopramide and pimozide failed to consistently antagonise peri-oral movements when similarly combined with GABA, serotonin or quipazine. It is suggested that, in addition to their known action on cerebral dopamine mechanisms, oxiperomide and tiapride may modify abnormal peri-oral movements by modulation of striatal gabaminergic and serotonergic mechanisms.     

Acute behavioral and cardiac effects of cocaine and alcohol combinations in humans

Subjects received acute doses of orally administered alcohol (0–1.0 g/kg) and intranasal cocaine (4–96 mg/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST performance, increased ratings of drunkenness, heart rate and skin temperature, and decreased blood pressure. Combining cocaine and alcohol attenuated the disruptions in DSST performance observed with alcohol alone, and either did not change or attenuated the improvements in performance observed with cocaine alone. Combining the drugs also attenuated effects observed with the drugs alone on skin temperature and, to a lesser extent, blood pressure. By contrast, drug combinations increased heart rate above levels observed when cocaine or alcohol were administered alone. Effects of the drug combinations on subject ratings were variable.     

美托洛尔对老年患者心功能及心率变异性的影响

目的评价美托洛尔对老年患者心功能及心率变异性(HRV)的影响。方法心血管病老年患者426例,年龄≥70岁,口服美托洛尔治疗12个月。观察治疗前、治疗12个月后BP、HR、HRV(340例窦性心律患者)、左室收缩末期容积(LVESV)和舒张末期容积(LVEDV)、左室射血分数(LVEF)和心排血量(CO)的变化。结果与治疗前比较,治疗后BP、HR明显降低(P<0.05),LVEDV及LVESV明显降低[(173.22±45.42)ml vs.(158.55±40.34)ml和(150.34±54.14)mlvs.(134.65±44.02)ml](P<0.05)],而LVEF和CO明显增加[(56.16±3.26)%vs.(60.25±4.05)%和(4.2±1.2)L vs.(5.4±1.9)L](P<0.05)]。HRV各参数均较治疗前明显升高。药物相关的不良反应无明显增加。结论对老年患者,美托洛尔降低心率和血压的同时,明显改善HRV及心功能。     

Cardiotoxicity of a new inotrope/vasodilator drug (SK&F 94120) in the dog

The cardiotoxicity and haemodynamic changes induced by IV administration of high doses of SK&F 94120, a novel positive inotrope/vasodilator, were studied in the dog. Inotropism was observed at a dose of 0.375 mg/kg. Mean blood pressure was reduced in a dose-related manner, reaching a nadir of 43.7 mm Hg at 24 mg/ kg. Heart rate was increased at doses of 1.5 mg/kg and above. ECG examination revealed a shortening of PR interval and an increase in T-wave amplitude. At doses of 15 mg/kg and above, occasional AV dissociation with accrochage were sometimes seen shortly after the start of the infusion. Ventricular extrasystoles were only seen at doses of 120 mg/kg and above. A dose-related increase in severity and incidence of haemorrhages, deposition of haemosiderin and fibroplasia were seen in the left ventricular endocardium and atrioventricular valves at doses of 15 mg/ kg and above. Focal myocardial necrosis, predominantly of the left ventricular papillary muscle, and mild periarteritis of medium-sized extramural arteries, mostly in the right atrium, were seen at doses of 45 mg/kg and above. Intimai proliferation of intra- and extramural coronary vessels was observed. A necrotising peri/panarteritis of these arteries was noted at doses of 200 and 400 mg/kg. The cardiotoxicity observed was considered to be due to the exaggerated pharmacologic effects seen at these high dose levels.     

The effects of captopril (SQ14,225) on the systemic and coronary haemodynamics of the intact anaesthetized dog

1. The effects of Captopril (SQ14,225), an inhibitor of angiotensin-converting enzyme, given intravenously in a dose of 0.3 mg/kg ws studied in intact anaesthetized dogs. 2. The drug caused a decrease in systemic and pulmonary arterial mean pressures, an increase in cardiac output, and hence a decrease in calculated systemic and pulmonary vascular resistances. A sustained tachycardia also occurred. 3. A minor, transient increase in coronary sinus flow was recorded, with a sustained decrease in calculated coronary vascular resistance. 4. No change was found in cardiac oxygen metabolism nor in calculated cardiac efficiency. 5. The plasma renin values increased in the control animals and those given the drug.     

射频消融对室上性心动过速(左侧旁道)患者左室功能的影响

目的 观察射频消融术（RFCA）对房室折返性心动过速（左侧旁道）[AVRT（L）]患者左室功能的影响。方法 利用二维和Doppler超声检查AVRT（L）患者手术前、后三天左室收缩功能及舒张期充盈情况,为提高敏感性,检查时增加了三级等长收缩运动。结果 （1）在各级运动中心率（HR）、收缩压（SBp)、舒张压（DBp)均显著增加,但三者均值分别不超过90bpm、160mmHg、95mmHg,运动后五分钟均恢复。（2）RFCA术前,后同级运动量时左室功能各参数无显著变化。结论 对于AVRT（L）患者,在有经验医师操作下,RFCA术中施放总能量在一定范围内时,对左室功能无影响。     

Electrophysiologic and hemodynamic effects of H 234/09 (almokalant), quinidine, and (+)-sotalol in the anesthetized dog.

The electrophysiologic and hemodynamic effects of H 234/09 (Almokalant), a novel class II antiarrhythmic agent, were studied in the anesthetized dog. H 234/09 (1.0 mumol/kg i.v.) significantly prolonged the atrial and ventricular effective refractory periods, the ventricular monophasic action potential duration, and the paced QT interval. At this dose, atrial, ventricular, and atrioventricular conduction was not affected, aortic blood pressure was not changed, and contractile force was transiently increased. The effects on cardiac repolarization and refractoriness induced by H 234/09 were both larger and more long lasting than the effects observed after quinidine (11.8 mumol/kg) and (+)-sotalol (9.7 mumol/kg). However, both quinidine and (+)-sotalol significantly reduced the aortic blood pressure and (+)-sotalol also decreased cardiac contractility. The effect of H 234/09 on atrial refractoriness was very little influenced by the paced heart rate and was twice as large as the corresponding effect in the ventricle. In conclusion, H 234/09 has electrophysiological properties suggestive of a class III antiarrhythmic. H 234/09 may have a favorable therapeutic profile compared to both quinidine and (+)-sotalol, especially for the treatment of atrial arrhythmias.     

Positive inotropy contributes to the hemodynamic mechanism of action of flosequinan (BTS 49465) in the intact dog.

Flosequinan (BTS 49465) is a putative, selective direct-acting balanced vasodilator currently undergoing evaluation for the treatment of congestive heart failure (CHF) and hypertension. We examined the pharmacologic action of flosequinan and compared it to milrinone and nitroprusside (SNP). In ferret papillary muscle, in vitro, flosequinan (1-100 microM) increased the rate of force development up to 116%. The effect was not blocked by nadolol (10 microM). Flosequinan was less effective than milrinone and SNP as a relaxant of canine renal and coronary arteries, in vitro, since 100 microM of flosequinan produced less than 50% relaxation of the arteries, whereas milrinone or SNP (100 microM) produced between 85 and 125% relaxation of the precontracted arteries. Flosequinan, SNP, and milrinone (100 microM) completely relaxed precontracted canine mesenteric veins. Fifteen minutes after intraduodenal administration (i.d.) of flosequinan (0.3, 1.0, and 3.0 mg/kg) to anesthetized dogs (n = 7), mean left ventricular (LV) dP/dT increased by 11, 27, and 54%, respectively, whereas total peripheral resistance (TPR) decreased by 4, 4, and 13%, and mean arterial pressure (MAP) decreased by 7, 14, and 23%, respectively. flosequinan was 4.6 times more potent as a positive inotrope than as a vasodilator. The hemodynamic profile of milrinone was similar to that of flosequinan, except milrinone produced greater increases in LV dP/dT and decreases in MAP and TPR. In contrast, SNP (1, 3, and 10 micrograms/kg/min i.v.) decreased TPR (7, 18, and 34%, respectively) and MAP (14, 32, and 41%, respectively) without any increase in LV dP/dT. In dogs with propranolol-induced heart failure (PIHF), flosequinan (1.0 and 3.0 mg/kg, i.d.) increased mean myocardial dP/dT by 54 and 84% (n = 5) and MAP, but decreased TPR. The data show that (a) the hemodynamic effects of flosequinan in the normal and PIHF dogs were primarily due to positive inotropy rather than to arterial vasodilation and (b) the positive inotropic effect of flosequinan is independent of catecholamines, since it occurred in dogs with PIHF. The beneficial effect of flosequinan in patients with CHF may not be mediated by balanced vasodilation.     

Prulifloxacin: in vitro (HERG current) and in vivo (conscious dog) assessment of cardiac risk

Prulifloxacin, a new thiazeto-quinoline derivative with antibiotic properties, was evaluated for cardiac risk both in vitro on the ether-à-go-go-related gene (HERG) K+ channel, and in vivo in the conscious dog monitored by telemetry. HERG current was measured from stably transfected human embryonic kidney (HEK) 293 cells by means of the patch-clamp technique. Application of AF 3013, the active metabolite of prulifloxacin, produced only minor reduction of HERG current amplitude (tail current=-40 mV), producing a maximum blockade of 12.3 +/- 3.3% at the highest concentration tested (335 microM). In comparison, ciprofloxacin also failed to produce a 50% inhibition of HERG current amplitude, although the maximum blockade was greater than that observed with prulifloxacin (47.6 +/- 1.9% at the highest concentration tested (335 microM). In contrast, moxifloxacin blocked HERG current amplitude with an IC50 value of 74.7 microM. Prulifloxacin had no effect on the QTc interval (Fridericia's) following 5 days of repeated oral administration (150 mg/kg/day) in the conscious dog monitored by telemetry. These findings suggest that prulifloxacin is not likely to prolong the QT interval.     

Electrocardiographic and hemodynamic effects of tocainide (W-36095) in man

Summary Tocainide is a new antiarrhythmic drug with a chemical structure related to that of lidocaine. In the present study, healthy volunteers were investigated after infusion of tocainide 450 mg over 45 min. In nine subjects His bundle electrograms, sinus recovery time and ventricular effective refractory periods were recorded. No major changes were seen. In eight cases the hemodynamic effects at rest and during exercise were studied. No significant circulatory effects were observed. No clinically important side-effects were noted.