Ouabain-induced Arrhythmias Research Articles

Effects of mediator antagonists on ischemic—and ouabain-induced cardiac arrhythmias in sensitized and non-sensitized guinea-pigs

Effects of mediator antagonists on ischemic—and ouabain-induced cardiac arrhythmias in sensitized and non-sensitized guinea-pigs

Significance of the number of stimuli to initiate ouabain-induced arrhythmias in the intact heart.

Ouabain-induced arrhythmias are a well-known model used to study triggered activity resulting from delayed afterdepolarizations. In the intact heart, initiation of these arrhythmias is promoted by pacing, especially at fast rates. However, the relevance of the number of stimuli is unknown. In conscious dogs with formalin-induced atrioventricular block, we investigated the effect of variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at progressive levels of ouabain intoxication, and 2) the induction of sustained ventricular tachycardia (VT). Twenty experiments were analyzed. Ouabain was administered as a bolus of 40 micrograms/kg followed by continuous infusion. Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until completion or induction of VT. When VT could not be initiated, the experiment was repeated at least 1 week later, adding 5-10 micrograms/kg ouabain to the bolus and increasing the infusion rate correspondingly. This was repeated until VT could be induced. Four interstimulus intervals (200, 400, 600, and 800 msec) and seven numbers of stimuli (5, 10, 20, 35, 50, 100, and 150) were given in two pacing protocols. The effect of these protocols on 1) the number of induced beats per stimulation train, 2) their first postpacing interval, and 3) induction of VT were studied. Initiation of VT occurred after 75 +/- 42 minutes. The bolus of ouabain needed to induce VT was inversely related to the body weight of the animals. Progression of ouabain intoxication resulted in 1) a significant increase in the number of induced beats per stimulation train and 2) a significant shortening of the first postpacing interval. Stimulation at a faster rate and/or more stimuli resulted in 1) a significantly pronounced increase in the number of induced beats at the higher levels and 2) a significantly shorter first postpacing interval at successive levels of ouabain intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

ICI 181,037: A Novel Eukalemic Diuretic with Antiarrhythmic Activity.

ICI 181,037, the most active compound from a series of 1,1-diarylcarbin-1-ol-2 amines, was evaluated for diuretic and cardiovascular activity. In saline-loaded rats, the magnitude of water diuresis and saluresis produced by ICI 181,037 (10 mg/kg, p.o.) was equal to that of hydrochlorothiazide. Water diuresis and saluresis produced by ICI 181,037 were enhanced with SKF 525A, ampicillin or neomycin plus lincomycin, suggesting that ICI 181,037 is an active diuretic. In conscious dogs, the saluretic activity of ICI d-181,037 (5 mg/kg, p.o.) was about 80% of the corresponding hydrochlorothiazide value, whereas the l-isomer demonstrated only minimum saluretic activity. In both rats and dogs, the concurrent kaliuresis after ICI 181,037 or its enantiomers was minimal as compared to hydrochlorothiazide. Following chronic dosing with diuretic doses, the basal levels of plasma potassium in dogs were not altered. In amphibian in vitro models for mimicking mammalian nephron, ICI 181,037 and its enantiomers demonstrated antinatriferic and antichloriferic activities, suggesting multiple renal sites of action for this agent. Racemic ICI 181,037 and its isomers reversed ouabain-induced arrhythmia in dogs and/or reduced the ouabain-induced mortality in mice after intravenous administration. It is concluded that ICI 181,037, particularly its d-isomer, is a novel eukalemic diuretic and possesses antiarrhythmic activity.

The in vivo response of ouabain-induced arrhythmias to pacing: Acceleration instead of termination

In vitro, arrhythmias that result from triggered activity based on delayed afterdepolarizations can be reproducibly terminated by pacing. We studied the effect of similar pacing protocols on ouabain-induced ventricular tachycardia (VT) in the intact canine heart. The experiments were performed in 17 conscious dogs that had surgically induced artioventricular block. The pacing protocol included 1, 2, or 20 stimuli and also continous stimulation during 15, 60, and 120 seconds with interstimulus intervals varying between 500 and 200 msec. A total of 331 stimulation trains were given. The cycle length of the ouabain-induced VT was compared before and after pacing. The mean R-R interval of the induced VT was 380 ± 80 msec. Termination was only observed in 3% of the pacing experiments and was not reproducible. The common response to pacing was a shortening in cycle length of VT that resulted in R-R intervals of 300 ± 50 msec ( p ≤ 0.001). Acceleration was dependent on duration of stimulation. A decrease in the interstimulus interval resulted in shortening of both the first postpacing interval and the cycle length of VT after pacing. These concordant relations were independent of the pacing modes. In conclusion, pacing of ouabain-induced VT in the intact heart rarely results in termination of the arrhythmia. Acceleration of VT is the rule. This finding may be of help in differentiating triggered activity that results from delayed afterdepolarizations from other arrhythmogenic mechanisms.

Ouabain-induced arrhythmias and diminished coronary flow: Effect of propranolol, verapamil and indomethacin: Ralph D. Tanz. Department of Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon (97201) USA

Ouabain-induced arrhythmias and diminished coronary flow: Effect of propranolol, verapamil and indomethacin: Ralph D. Tanz. Department of Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon (97201) USA

Antiarrhythmic effects of prostaglandins E 2 and I 2 on ouabain-induced cardiac arrhythmias in cats: Effect of vagotomy and adrenergic neuron blockade

The effects of i.v. prostaglandins (PGs) E 2 and I 2 on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and guanethidine-pretreatment interventions were employed to elucidate the involvement of vagal and sympathetic neural influences in these effects. PGE 2 (1 μg/kg/min i.v. infusion for 5 min) and PGI 2 (4–16μg/kg i.v. bolus injections) effectively suppressed the ouabain-induced arrhythmias in a control group of cats. The bilateral vagotomy or guanethidine-pretreatment interventions did not significantly alter the antiarrhythmic effects of PGE 2 and PGI 2. It is concluded that the presence of functionally intact sympathetic and vagal nerve supply to the heart is not a prerequisite for the antiarrhythmic effects of i.v. administered PGE 2 and PGI 2. The possible role of direct action of these PGs on the myocardium is discussed.

Ｃｅｌｉｐｒｏｌｏｌの薬理学的研究 ＩＩＩ 心選択性β‐遮断薬Ｃｅｌｉｐｒｏｌｏｌの心血管および腎機能に対する作用並びに抗不整脈作用

Effects of celiprolol on the cardiovascular system and renal function, and its antiarrhythmic effects were studied. 1. In anesthetized dogs, celiprolol (0.01-3 mg/kg, i.v.) dose-dependently depressed the maximum rate of rise of left ventricular pressure, cardiac output and cardiac work less severely than propranolol and atenolol. 2. Celiprolol (0.01 mg/kg, i.v.) decreased the myocardial oxygen consumption in anesthetized dogs as potently as propranolol. 3. Celiprolol (0.03-3 mg/kg, i.v.) tended to increase femoral blood flow. Celiprolol (1 mg/kg, i.v.) increased common carotid blood flow. 4. Celiprolol decreased urine volume and urinary excretion of Na+ and Cl- at doses of 1 and 10 mg/kg and increased the sodium reabsorption rate at a dose of 10 mg/kg in anesthetized dogs, whereas it produced no change in plasma renin activity. 5. Celiprolol inhibited both halothane-adrenaline arrhythmia in dogs and ouabain-induced arrhythmia in rabbits. Its antiarrhythmic effects were 1/10-1/3 as potent as those of propranolol. 6. Celiprolol suppressed the maximum rate of rise of action potential at a concentration of 3 x 10(-4) M, which was 30 times as high as that of propranolol. Celiprolol (3 x 10(-5)-3 x 10(-4) M) dose-dependently shortened the effective refractory period (ERP), but it produced no change in the ratio of ERP to action potential duration. 7. These results suggest that celiprolol may be a useful drug for the treatment of ischemic heart disease and some types of arrhythmia, and that it has only a little influence on renal function.

The Effect of an Entrainment Protocol on Ouabain‐Induced Ventricular Tachycardia

Overdrive stimulation of reentrant ventricular tachycardias (VT) may result in entrainment and/or termination of these arrhythmias. We investigated whether surface ECG criteria of entrainment can also be observed in nonreentrant VT. For this purpose ouabain-induced tachycardias were used that are considered to be based on delayed afterdepolarizations. In nine conscious dogs, having surgically induced complete AV block, pacing was performed using trains of 20 stimuli from a site distant to the origin of the VT. The pacing intervals were shortened in steps of 5-10 msec, until complete capture from the pacing site or termination of the VT was obtained. During stimulation variable fusion was seen and complete capture of the ventricles from the pacing site occurred just after a slight decrease in pacing cycle length (20 +/- 10 msec). Overdrive stimulation resulted only in 1 out of 58 stimulation trains in termination of VT. Following stimulation it was observed that: (1) The length of the first postpacing interval was significantly longer (P less than 0.001) than both the mean prepacing VT cycle length and interstimulus interval; (2) A change in QRS configuration occurred after 57% of the stimulation trains; (3) The VT accelerated slightly in comparison to the prepacing rate (P less than 0.05); and (4) The length of the first postpacing interval and the mean R-R interval of the VT postpacing were directly related to the interstimulus interval (r = 0.82 and 0.97, respectively). In conclusion, overdrive stimulation of ouabain-induced arrhythmias did not result in entrainment or in termination of the tachycardia. Instead, other responses were seen that may be of help in differentiating between arrhythmias caused by delayed afterdepolarizations and reentry.

Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents.

To determine specificity of rodent models of arrhythmia for different Vaughan Williams classes of antiarrhythmic drugs, we tested 17 drugs from the four classes in one in vitro and four in vivo models. In the mouse chloroform-induced ventricular fibrillation model and in the guinea pig ouabain-induced arrhythmia model, drugs of classes I (amefalone, aprindine, lidocaine, mexiletine, phenytoin, procainamide, or quinidine), II (metoprolol or propranolol), and IV (bepridil) were active. Class III drugs (bretylium, clofilium, or melperone did not suppress ouabain arrhythmias, but were active in the mouse chloroform model. In the rat coronary artery ligation model, disopyramide (class I), amefalone and melperone significantly (P less than 0.05) reduced the number of extrasystoles. Propranolol, sotalol, and verapamil (class IV) were less effective. In the rat coronary artery ligation/reperfusion model, all four classes of antiarrhythmic agents were active in vitro (isolated heart) and in vivo (anesthetized rat). Thus, one model of automaticity, the guinea pig ouabain model, detected class I, II, and IV drugs, whereas another automaticity model, the mouse chloroform model, also detected class III agents. The model of reentry induced by ischemia plus reperfusion (rat coronary artery ligation reperfusion) can be recommended as a screen for new antiarrhythmic agents based on its sensitivity to all four classes of antiarrhythmic drugs. The Vaughan Williams class of an antiarrhythmic agent must be determined, however, by additional mechanism studies.

Effects of dantrolene sodium in rodent models of cardiac arrhythmia

Dantrolene sodium has been compared with reference antiarrhythmic agents in rodent models of cardiac arrhythmia. In a coronary-artery-ligation model in rats, dantrolene sodium (3, 10 and 20 mg/kg i.v.) significantly decreased extrasystoles, episodes of ventricular tachyarrhythmia, and frequency, duration, and total episodes of ventricular fibrillation in a dose-dependent manner. In an electrically induced fibrillation model in rats, dantrolene sodium (10 and 20 mg/kg i.v.) significantly raised ventricular fibrillation threshold in a dose- and time-dependent manner. In contrast to its activity in these models, dantrolene sodium was not active in two chemically induced models involving automaticity. Aconitine-induced arrhythmias in rats and mice and ouabain-induced arrhythmias in guinea pigs were not suppressed by i.v. (10 or 20 mg/kg) or i.p. (100–300 mg/kg) doses of the drug. These results show that the antiarrhythmic potential of dantrolene sodium, predicted by in vitro Class III and Class IV electrophysiological effects, is expressed in whole animal models.

The protective action of R56865 against ouabain-induced intoxication in rat heart isolated atria and ventricles

The action of R56865 has been examined on the contractile effects produced by ouabain concentrations interacting with high (3 μM) and low (300 μM) affinity digitalis receptors on electrically stimulated ventricular strips isolated from rat. R56865 1 μM reduced the increase in resting tension produced by ouabain 300 μM and left unalterated the inotropic effect evoked by ouabain 3 and 300 μM was reduced by higher concentrations (3 and 6 μM) of R56865. The action of R56865 was also studied on ouabain-induced intoxication in electrically stimulated and spontaneously beating atria of rat. On electrically stimulated (3 Hz) whole atria, R56865 0.3 μM reduced the maximal increase in resting tension produced by ouabain 300 μM and delayed the time to onset of the ouabain-induced arrhythmias but did not affect ouabain's inotropic effect. Higher concentrations of R56865 were required to reduce the inotropic effect of ouabain. The protective action of R56865 against ouabain-induced intoxication was most pronounced on spontaneously beating atria where it reduced spontaneous rate of beats. Experiments in electrically driven left atria indicated that only a part of the protective effect of R56865 could be related to its bradycardic action. The effect of R56865 was also examined on ouabain-induced inhibition of sodium pump in human red blood cells. R56865 μM did not modify the inhibition produced by ouabain (from 0.3 to 10 nM), this indicates that the protective action of R56865 against ouabain-induced intoxication is not due to an interaction with the inhibitory effect of ouabain on sodium pump.

Efficacy and Plasma Concentrations of SC-36602 in Canine Models of Ventricular Arrhythmia

The antiarrhythmic effectiveness of a new class I agent, SC-36602, was evaluated in two canine models of ventricular arrhythmia. In a Harris coronary ligation-induced arrhythmia model, SC-36602 significantly reduced ectopic rate at doses of 8 mg/kg i.v. and 15, 20 and 30 mg/kg per os. In a ouabain-induced arrhythmia model, a 9 mg/kg i.v. dose of SC-36602 had a sustained (greater than or equal to 60 min) antiarrhythmic effect. The approximate plasma concentration of SC-36602 necessary for measurable antiarrhythmic activity was estimated to be 2-7 micrograms/ml after either i.v. or oral administration. No adverse cardiovascular or central nervous system effects were observed in conscious or anesthetized dogs in response to SC-36602.

Pharmacological studies of indole alkaloids obtained from domestic plants, Uncaria rhynchophylla Miq. and Amsonia elliptica Roem. et Schult

Pharmacological studies on hirsutine (HS), hirsuteine (HST), rhynchophylline (RP), isorhynchophylline (IRP) and dihydrocorynantheine (DCT) which were isolated from the domestic plant Uncaria rhynchophylla Miq. and beta-yohimbine (beta-Y) which was isolated from the domestic plant Amsonia elliptica Roem. et Schult. were carried out. These alkaloids showed a mild central depressive effect in mice, a week non-competitive anti-spasmodic action in the mouse intestine, and a hypotensive effect in rats. Since beta-Y showed alpha-adrenoceptor blocking action, the hypotensive effect of beta-Y may be partly due to the vasodilative effect induced by its alpha-adrenoceptor blocking action. HS and beta-Y showed a preventive effect on the development of gastric erosions in mice. HS had antiarrhythmic effects on both aconitine-induced arrhythmias in mice and ouabain-induced arrhythmias in guinea pigs. The potency of the antiarrhythmic effects induced by HS was approximately the same as that of ajmaline, an indole alkaloid. Since HS did not show beta-adrenoceptor blocking action, the antiarrhythmic effects of HS would not be due to its beta-adrenoceptor blocking effect.

Effects of the myocardial-selective alpha 1-adrenoceptor antagonist UK-52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs.

1. Adrenaline-induced arrhythmias in anaesthetized dogs respired with halothane were attenuated in 3 groups of 6 dogs by either UK-52046, 3.8 +/- 1.4 micrograms kg-1 (mean +/- s.e.mean), atenolol 14.6 +/- 2.1 micrograms kg-1, or a combination containing equal amounts of the two drugs of 0.36 +/- 0.1 microgram kg-1. The pressor response to adrenaline was reduced (P less than 0.01) by UK-52046 but not by atenolol or the combination of both drugs. 2. In a group of 6 dogs with multiventricular ectopic beats 24 h after coronary artery ligation (CAL), UK-52046, 32 micrograms kg-1, increased the number of sinus beats in each 5 min period from 137 +/- 47 to 662 +/- 99 (P less than 0.01); this was associated with a significant (P less than 0.01) fall in blood pressure. Atenolol in doses of up to 800 micrograms kg-1 had no effect. 3. UK-52046, 3.7 +/- 1.4 micrograms kg-1, prevented adrenaline-induced arrhythmias 3-4 days after CAL in 6/6 conscious dogs; atenolol in doses of up to 100 micrograms kg-1 produced an 84.4 +/- 7.4% reduction in the number of ventricular ectopic beats. A combination containing 3.7 +/- 1.1 micrograms kg-1 of each drug prevented the arrhythmia in 6/6 dogs. The pressor response to adrenaline was attenuated (P less than 0.05) by UK-52046, but resting blood pressure was unaffected by the different treatments. An increase (P less than 0.01) in heart rate was associated with both UK-52046 and the combination. 4. Neither UK-52046 (doses up to 64 micrograms kg-1) nor atenolol (up to 800 micrograms kg-1) had any effect upon ouabain-induced arrhythmias in 2 groups of 6 anaesthetized dogs. 5. In a study of the early (1a/1b) arrhythmias of acute myocardial ischaemia, the total number of ventricular ectopic beats occurring within 30 min of CAL was not reduced by 4 micrograms kg-1 UK-52046 but fell (P less than 0.01 compared with placebo) after 8 micrograms kg-1 [median values with ranges for placebo, 4 micrograms kg-1 and 8 micrograms kg-1 respectively 190 (4-674), 246 (9-1204) and 12 (1-154)]. Both doses of UK-52046 were associated with significant falls in blood pressure. 6. The arrhythmias produced by programmed electrical stimulation were studied in 2 groups of 6 conscious dogs, 7-30 days after CAL. With placebo, 4/6 dogs remained unchanged and 2 died: UK-52046 prevented arrhythmias in 2/6, 2 remained unchanged and 2 died (P = 0.29). Compared with placebo, blood pressure fell with doses greater than 4jg kg- '. 7. These results indicate antiarrhythmic effects of UK-52046 in a number of experimental models and suggest an enhanced role of alpha-receptors in the genesis of ischaemia-related arrhythmias. In several of the models used, UK-52046 produced haemodynamic changes in keeping with peripheral alpha-adrenoceptor antagonism.

Modified method for the production of cardiac arrhythmias by ouabain in anesthetized cats

A modified method of producing ouabain-induced cardiac arrhythmias in chloralose-anesthetized cats has been developed, whereby prolonged arrhythmias with low incidence of mortality (12%) are observed. Furthermore, the employment of a modified arrhythmia scale in the present model allowed a quantitative estimation of antiarrhythmic efficacy of test drugs and also made it possible to unravel the arrhythmogenic nature of these substances. This improved method could be conveniently used for the quantitative screening of both the antiar-rhythmic or the arrhythmogenic nature of test drugs.

Effect of some non-steroidal anti-inflammatory drugs on ouabain-induced arrhythmias in guinea-pigs.

1. Effects of some non-steroidal anti-inflammatory drugs on ouabain-induced arrhythmias in guinea-pigs were studied. 2. Ventricular premature beats, ventricular fibrillation and cardiac arrest were induced in pentobarbitone-anaesthetized guinea-pigs by a slow intravenous infusion of ouabain. 3. Aspirin and indomethacin were found to accord a significant protection to the guinea-pigs against arrhythmias whereas ketoprofen was found to be ineffective. 4. It is concluded that the protective effect of aspirin and indomethacin may be due to inhibition of synthesis and release of thromboxane A2 from the myocardium.

Protective effect of verapamil upon ouabain-induced cardiac arrhythmias.

Protective influence of verapamil upon ouabain-induced cardiac arrhythmias was investigated in anesthetized (alpha-chloralose 60 mg/kg and urethane 500 mg/kg) open-chest guinea pigs. Verapamil in doses between 100 and 150 micrograms/kg significantly increased (80-90%) the dose of ouabain, necessary to cause ventricular arrhythmias. This was also associated with a larger survival rate. A larger dose of verapamil (225 micrograms/kg) caused a further increase in the dose of ouabain, necessary for the initiation of arrhythmias, but in all the cases second or third degree heart block occurred. Verapamil (150 micrograms/kg) also prevented the development of fatal arrhythmias and death, when it was administered at the onset of ventricular ectopy. However, once the arrhythmias were firmly established, verapamil was ineffective in reversing the toxic response. The data suggests that verapamil exerts a protective effect against the development of digitalis-induced cardiac arrhythmias in doses which are comparable to therapeutic levels in humans. The larger doses of verapamil, however, will be contradicted because of the slowing of AV node and the likelihood of complete heart block.

Actions of a Newly Synthesized Compound (711389-S) on Various Types of Experimentally Induced Arrhythmias in Mammalian Species In Situ

We examined effects of 711389-S, a new antiarrhythmic agent, on ouabain-induced arrhythmias in dogs and guinea-pigs, aconitine-induced arrhythmias in dogs and mice, adrenaline-induced arrhythmias in dogs under an anesthetized condition, and arrhythmias induced by coronary artery ligation and occlusion by a glass bead in dogs under conscious and un-restrained conditions. 711389-S (1-3 mg/kg, i.v.) decreased the number of ventricular extrasystoles induced by ouabain in dogs, and the doses of ouabain required to induce various types of arrhythmias were increased by pretreatment of guinea-pigs with intraduodenal application of 71 1389-S (5-10 mg/kg). In mice, 711389-S (3 mg/kg, i.v. or 10 mg/kg, p.o.) significantly prolonged the time to onset of arrhythmias induced by aconitine infusion. Atrial fibrillation induced by a topical application of aconitine on the atrium was blocked by 711389-S (1 mg/kg, i.v.) in dogs. 711389-S (1-3 mg/kg, i.v.) depressed arrhythmias induced by adrenaline and restored the sinus rhythm by significantly decreasing the number of ventricular ectopic beats induced by coronary ligation or occlusion in dogs. Oral administration of 711389-S (10-30 mg/kg) in dogs markedly depressed the ventricular ectopic beats induced by coronary ligation. The half decay time of 711389-S after a single bolus injection of 711389-S ranged from 60 to 80 min. Results indicate that 711389-S has similar antiarrhythmic effects to those of other Class I antiarrhythmic agents in situ, and they suggest that this compound might have potential usefulness as a new type of antiarrhythmic agent for clinical use.

Actions of a newly synthesized compound (711389-S) on various types of experimentally induced arrhythmias in mammalian species in situ.

We examined effects of 711389-S, a new antiarrhythmic agent, on ouabain-induced arrhythmias in dogs and guinea-pigs, aconitine-induced arrhythmias in dogs and mice, adrenaline-induced arrhythmias in dogs under an anesthetized condition, and arrhythmias induced by coronary artery ligation and occlusion by a glass bead in dogs under conscious and un-restrained conditions. 711389-S (1-3 mg/kg, i.v.) decreased the number of ventricular extrasystoles induced by ouabain in dogs, and the doses of ouabain required to induce various types of arrhythmias were increased by pretreatment of guinea-pigs with intraduodenal application of 711389-S (5-10 mg/kg). In mice, 711389-S (3 mg/kg, i.v. or 10 mg/kg, p.o.) significantly prolonged the time to onset of arrhythmias induced by aconitine infusion. Atrial fibrillation induced by a topical application of aconitine on the atrium was blocked by 711389-S (1 mg/kg, i.v.) in dogs. 711389-S (1-3 mg/kg, i.v.) depressed arrhythmias induced by adrenaline and restored the sinus rhythm by significantly decreasing the number of ventricular ectopic beats induced by coronary ligation or occlusion in dogs. Oral administration of 711389-S (10-30 mg/kg) in dogs markedly depressed the ventricular ectopic beats induced by coronary ligation. The half decay time of 711389-S after a single bolus injection of 711389-S ranged from 60 to 80 min. Results indicate that 711389-S has similar antiarrhythmic effects to those of other Class I antiarrhythmic agents in situ, and they suggest that this compound might have potential usefulness as a new type of antiarrhythmic agent for clinical use.

The vagal involvement in the antiarrhythmic and arrhythmogenic effects of prostaglandin F 2α on ouabain-induced cardiac arrhythmias in cats

The effects of prostaglandin F 2α (PGF 2α) on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and atropine intervention were employed to elucidate the involvement of vagal neural influences. PGF 2α (2–16 μg/kg i.v. bolus) predominantly suppressed the ouabain-induced ventricular and supraventricular arrhythmias and less commonly aggravated them in vagi-intact cats. The antiarrhythmic effect of PGF 2α was considerably, but not statistically significantly, decreased while its arrhythmogenic effect was significantly (p < 0.05) increased in atropine-pretreated group. In vagotomised group PGF 2α failed to abolish the arrhythmias but it aggravated them to a degree comparable to that observed in vagi-intact group. It is concluded that the PGF 2α exhibits both antiarrhythmic and arrhythmogenic properties and these are largely due to elicitation of two opposing neural reflexes — one being protective and another being deleterious to ouabain-induced arrhythmias.