Coronary Ligation Arrhythmia Research Articles

Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias and reperfusion-induced arrhythmias in anesthetized rats.

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats. In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 micromol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 micromol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained. In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 micromol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 micromol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure. We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.

Antiarrhythmic effects of a novel class III drug, KCB-328, on canine ventricular arrhythmia models.

KCB-328 is a newly synthesized class III drug. To determine whether this drug has antiarrhythmic or proarrhythmic effects, we used canine ventricular arrhythmia models induced by coronary ligation and reperfusion, programmed electrical stimulation (PES), two-stage coronary ligation, digitalis, or epinephrine. KCB-328, in an intravenous infusion of 0.5 mg/kg/30 min, prolonged the QTc interval only 11%, but had antiarrhythmic effects on the reentry arrhythmias induced by PES (12 of 12 dogs with old myocardial infarction; p < 0.05). KCB-328, in an infusion of 1 mg/kg/h, suppressed the occurrence of fatal ventricular fibrillation (VF) induced by coronary ligation and reperfusion under either halothane anesthesia (p < 0.05) or pentobarbital anesthesia (p < 0.05). Under the halothane anesthesia, KCB-328 alone showed proarrhythmic effects [i.e., induction of ventricular premature contractions (VPCs)], but it did not induce a more severe effect such as torsades de pointes-type ventricular tachycardia (VT). In addition, KCB-328 had weak antiarrhythmic effects on the automaticity arrhythmias induced by 24-h coronary ligation but was effective neither on 48-h coronary ligation arrhythmias nor on the digitalis- and epinephrine-induced arrhythmias. Our results indicate that KCB-328 has powerful antiarrhythmic effects with fewer proarrhythmic potencies.

Effects of a cardioselective M2 receptor antagonist, AF-DX 116, on ventricular arrhythmias in dogs.

AF-DX 116 is a cardioselective M2 receptor antagonist and, thus, it should induce sinus tachycardia. Since normal ventricular automaticity is suppressed by atrial overdriving, AF-DX 116 might become an antiarrhythmic drug and act by increasing the sinus node automaticity. Ventricular arrhythmia models used in this study were induced either by two-stage coronary ligation, digitalis, or adrenaline in beagle dogs. AF-DX 116 (0.3 mg/kg i.v.) tended to increase the sinus rate of the conscious beagles compared to the pre-drug level (although the effect was not significant) but had no antiarrhythmic effect (i.e., there was no decrease in the arrhythmic ratio defined as the number of PVC divided by the total heart rate) on the ventricular tachycardia (VT) induced 24 h after aseptic ligation of the left anterior descending coronary artery. AF-DX 116 did not alter the blood pressure. The drug also did not suppress digitalis-induced VT and did not increase the atrial rate, which was already increased to about 210 beats/min by ouabain. AF-DX 116 decreased the arrhythmic ratio, 9 min after bolus injection, and increased the atrial rate in the adrenaline VT model. The maximum plasma concentration of AF-DX 116 reached nearly 1microg/ml 1 min after the bolus injections in the digitalis and adrenaline arrhythmia experiments, which is close to the maximum concentration expected to be attained in the clinical application of this drug. Although AF-DX 116 increased the heart rate, under the present experimental conditions of increased atrial rate, the extent of tachycardia was not strong enough to suppress the 24-h coronary ligation and digitalis-induced arrhythmias. The late onset of the antiarrhythmic effect of AF-DX 116 on adrenaline-induced arrhythmia cannot be explained by the overdrive suppression mechanism.

Effects of a new forskolin derivative, NKH477, on canine ventricular arrhythmia models.

Using two-stage coronary ligation-, digitalis- and epinephrine-induced canine ventricular arrhythmia models, we examined whether a new positive inotropic agent, NKH477, 6-(3-dimethylaminopropionyl)forskolin hydrochloride, a water-soluble derivative of forskolin, had deleterious effects on arrhythmias. NKH477 increased heart rate (HR) and decreased blood pressure (BP) in dogs with all the arrhythmia models. Unexpectedly, NKH477 suppressed digitalis- and epinephrine-induced arrhythmias, but did not suppress two-stage coronary ligation arrhythmia or aggravate it. These results indicate that NKH477, unlike other new positive inotropic agents such as amrinone, milrinone, sulmazole and vesnarinone, did not worsen these arrhythmias; thus, NKH477 may be a useful positive inotropic agent with little arrhythmogenic effect.

Effects of a new class I antiarrhythmic drug bidisomide on canine ventricular arrhythmia models.

The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent, bidisomide, alpha-(2-[acetyl(1-methylethyl)amino]ethyl)-alpha-(2- chlorophenyl)-1-piperidinebutanamide, were investigated. To determine the anti-arrhythmic effects, spontaneously occurring adrenaline-, digitalis- and two-stage coronary ligation-induced arrhythmias were used. Bidisomide suppressed these three arrhythmia models. The antiarrhythmic plasma concentration, IC50, of bidisomide for digitalis-induced arrhythmia was 22.1 micrograms/ml, and those calculated for intravenous bidisomide in 24 h and 48 h coronary ligation-arrhythmias were 15.1 and 11.6 micrograms/ml and that calculated for oral bidisomide in 24 h coronary ligation-arrhythmia was 5.4 micrograms/ml and that for adrenaline induced arrhythmia was 58.7 micrograms/ml. In the blood perfused sinoatrial node and papillary muscle preparations, bidisomide decreased the sinoatrial rate and contractile force and increased the intraventricular conduction time and coronary blood flow. These results indicate that bidisomide is similar to other class I antiarrhythmic agents such as pirmenol and KW-3401 in its antiarrhythmic profile and is expected to become a clinically useful antiarrhythmic drug.

Antiarrhythmic effects of MS-551, a new class III antiarrhythmic agent, on canine models of ventricular arrhythmia.

The antiarrhythmic effects of MS-551, which prolongs cardiac action potential duration without affecting the maximum upstroke velocity of the action potential, were assessed in three different canine ventricular arrhythmia models: 1) ventricular tachycardia (VT) induced by electrical stimuli 3-5 days after myocardial infarction, 2) spontaneous ventricular tachyarrhythmias 24-48 hr after two-stage coronary ligation and 3) ventricular tachyarrhythmias induced by digitalis. Intravenous administration of MS-551 (0.1-1 mg/kg) decreased the susceptibility in 10 dogs out of 13 to VT or ventricular fibrillation evoked by programmed electrical stimulation (PES) delivered to the ventricular septum 3-5 days after myocardial infarction. Oral administration of MS-551 (3 mg/kg) also decreased the susceptibility to VT evoked by PES in 7 out of 10 conscious postinfarction dogs. Concurrently, intravenous (0.1-1 mg/kg) or oral (3 mg/kg) administration of MS-551 produced increases in the ventricular effective refractory periods (ERP) by 7 +/- 1% - 17 +/- 3% or 13 +/- 2%, respectively. Similarly, d-sotalol (0.3-3 mg/kg, i.v. and 10 mg/kg, p.o.) decreased the susceptibility to VT with increased ERP. However, MS-551 (1 and 10 mg/kg, i.v.) failed to inhibit both canine two-stage coronary ligation arrhythmia and digitalis arrhythmia. These results suggest that MS-551 is a pure class III antiarrhythmic drug which may be effective in the treatment of life-threatening reentrant tachyarrhythmias, but not in automaticity arrhythmias.

Antiarrhythmic Effects of MS-551, a New Class Ill Antiarrhythmic Agent, on Canine Models of Ventricular Arrhythmia

The antiarrhythmic effects of MS-551, which prolongs cardiac action potential duration without affecting the maximum upstroke velocity of the action potential, were assessed in three different canine ventricular arrhythmia models: 1) ventricular tachycardia (VT) induced by electrical stimuli 3–5 days after myocardial infarction, 2) spontaneous ventricular tachyarrhythmias 24–48 hr after two-stage coronary ligation and 3) ventricular tachyarrhythmias induced by digitalis. Intravenous administration of MS-551 (0.1–1 mg/kg) decreased the susceptibility in 10 dogs out of 13 to VT or ventricular fibrillation evoked by programmed electrical stimulation (PES) delivered to the ventricular septum 3–5 days after myocardial infarction. Oral administration of MS-551 (3 mg/kg) also decreased the susceptibility to VT evoked by PES in 7 out of 10 conscious postinfarction dogs. Concurrently, intravenous (0.1–1 mg/kg) or oral (3 mg/kg) administration of MS-551 produced increases in the ventricular effective refractory periods (ERP) by 7 ± 1%–17 ± 3% or 13 ± 2%, respectively. Similarly, d-sotalol (0.3–3 mg/kg, i.v. and 10 mg/kg, p.o.) decreased the susceptibility to VT with increased ERP. However, MS-551 (1 and 10 mg/kg, i.v.) failed to inhibit both canine two-stage coronary ligation arrhythmia and digitalis arrhythmia. These results suggest that MS-551 is a pure class III antiarrhythmic drug which may be effective in the treatment of life-threatening reentrant tachyarrhythmias, but not in automaticity arrhythmias.

Antiarrhythmic Plasma Concentrations of NIK-244 on Canine Ventricular Arrhythmias

Using two-stage coronary ligation-, digitalis-, and epinephrine (EPI)-induced canine ventricular arrhythmias, we examined antiarrhythmic effects of NIK-244 and determined the minimum effective plasma concentration for each arrhythmia model. NIK-244 suppressed coronary ligation- and digitalis-induced arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-h and 48-h coronary ligation and digitalis were 0.41 +/- 0.10 (by 1 mg/kg i.v.), 0.70 +/- 0.13 (by 1 mg/kg i.v.), and 0.21 +/- 0.08 (by 0.5 mg/kg i.v.) microgram/ml, respectively (mean +/- SD of the mean, n = 6). The concentration for digitalis-induced arrhythmia was significantly lower than those for coronary ligation arrhythmias. NIK-244 was not effective on EPI arrhythmia, and 1 mg/kg worsened the arrhythmia to ventricular fibrillation in three of six dogs. This pharmacologic profile is similar to those of disopyramide, procainamide, and SUN 1165. Since NIK-244 had no deleterious effects on blood pressure and sinus node activity, its clinical usefulness is expected.

Antiarrhythmic effect of a new class 1 antiarrhythmic drug, AN-132, on ventricular arrhythmias in beagles

Using two-stage coronary-ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in beagles, antiarrhythmic effects of AN-132 were examined, and the minimum effective plasma concentration for each arrhythmia model was determined. AN-132 suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-hour coronary ligation, 48-hour coronary ligation, digitalis, and adrenaline were 3.4-4.6, 1.5-2.3, 0.83, and 9.3 micrograms/ml, respectively. The concentration for adrenaline-induced arrhythmia was significantly higher than that of 24-hour coronary ligation arrhythmia, and it was also higher than that of digitalis arrhythmia. This pharmacologic profile is similar to those of pirmenol and mexiletine. Since AN-132 had no deleterious effects on the hemodynamics and the central nervous system, it may become a clinically useful antiarrhythmic drug.

Effects of KT-362, a New Na and Ca Influx and Ca Release Inhibitor, on Canine Ventricular Arrhythmias

AbstractAntiarrhythmic effects of the new drug KT-362. which was reported to suppress Na and Ca currents of cardiac cells and also to suppress intracellular Ca release in isolated smooth muscle preparations, were examined using two-stage coronary ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in the dog. Intravenous KT-362 at 10 mg/kg suppressed coronary ligation arrhythmia both at 24 and 48 hr after ligation, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation and 48 hr coronary ligation were 6.1±1.7 and 8.6±2.7 μg/ml, respectively. Antiarrhythmic effects were accompanied by transient hypotension. Oral administration of 70-100 mg/kg was also effective on 24 hr coronary ligation arrhythmia. However, there was no prominent hypotension in these experiments. Intravenous KT-362 at 3 mg/kg suppressed digitalis arrhythmia: and the minimum effective plasma concentration was 3.3±1.2 μg/ml, which was lower than the effective plasma concentrations for coronary ligation arrhythmias. Intravenous KT-362 at 1 mg/kg also suppressed adrenaline arrhythmia; and the minimum effective plasma concentration was 1.0±0.1 μg/ml, the lowest among the effective plasma concentrations. These pharmacological profiles of KT-362 are quite different from those of class 4 Ca antagonists, but similar to those of class 1 drugs such as propafenone. Though KT-362 has a hypotensive effect, it is effective on canine ventricular arrhythmias: thus its clinical usefulness for supraventricular and ventricular arrhythmias is expected

Effects of KT-362, a new Na and Ca influx and Ca release inhibitor, on canine ventricular arrhythmias.

Antiarrhythmic effects of the new drug KT-362, which was reported to suppress Na and Ca currents of cardiac cells and also to suppress intracellular Ca release in isolated smooth muscle preparations, were examined using two-stage coronary ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in the dog. Intravenous KT-362 at 10 mg/kg suppressed coronary ligation arrhythmia both at 24 and 48 hr after ligation, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation and 48 hr coronary ligation were 6.1 +/- 1.7 and 8.6 +/- 2.7 micrograms/ml, respectively. Antiarrhythmic effects were accompanied by transient hypotension. Oral administration of 70-100 mg/kg was also effective on 24 hr coronary ligation arrhythmia. However, there was no prominent hypotension in these experiments. Intravenous KT-362 at 3 mg/kg suppressed digitalis arrhythmia; and the minimum effective plasma concentration was 3.3 +/- 1.2 micrograms/ml, which was lower than the effective plasma concentrations for coronary ligation arrhythmias. Intravenous KT-362 at 1 mg/kg also suppressed adrenaline arrhythmia; and the minimum effective plasma concentration was 1.0 +/- 0.1 microgram/ml, the lowest among the effective plasma concentrations. These pharmacological profiles of KT-362 are quite different from those of class 4 Ca antagonists, but similar to those of class 1 drugs such as propafenone. Though KT-362 has a hypotensive effect, it is effective on canine ventricular arrhythmias; thus its clinical usefulness for supraventricular and ventricular arrhythmias is expected.

Antiarrhythmic Effect of a New Class 1 Antiarrhythmic Drug, Nicainoprol, on Canine Ventricular Arrhythmias

Using two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of nicainoprol were examined in dogs, and the minimum effective plasma concentration for each arrhythmia model was determined. Nicainoprol suppressed the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 48 hr coronary ligation, digitalis and adrenaline were 8.9 μg/ml (by 5 mg/kg, i.v.), 3.0 μg/ml (by 3 mg/kg, i.v.) and 2.7 μg/ml (by 3 mg/kg, i.v.), respectively. The concentration for coronary ligation arrhythmia was higher than those for the digitalis and adrenaline arrhythmias. This pharmacological profile is similar to those of aprindine and propafenone. Nicainoprol induced some central nervous system effect including vomiting in conscious coronary ligated dogs. Though intravenous nicainoprol (5 mg/kg) was not effective on 24 hr coronary ligation arrhythmia, an oral dose of 30 to 40 mg/kg was effective. These results indicate that it may become a clinically useful antiarrhythmic drug.

Effects of antiarrhythmic drugs on canine ventricular arrhythmia models

In order to compare and clarify the effects of various antiarrhythmic drugs, we examined drug effects on several canine arrhythmia models, simultaneously determining the minimum effective plasma concentrations. We used 1) two-stage coronary ligation arrhythmia, 2) digitalis arrhythmia, and 3) halothane-adrenaline arrhythmia. The following are, a summary of our results: Antiarrhythmic drugs of class 1 all suppressed digitalis arrhythmia, and except for lidocaine, also suppressed coronary ligation arrhythmia. Class 2 antiarrhythmic drugs, beta blockers, and class 4 antiarrhythmic drugs, Ca channel blockers, had common features of effectiveness, where they suppressed adrenaline arrhythmia in relatively low concentrations. Some differences among the antiarrhythmic effects of class 1 drugs could not be explained by their subclassification based either on action potential duration or kinetic properties of dissociation or association with Na channels. A new arrhythmia model for triggered activity in in vivo canine heart was developed, but drug effects on it does not seem to be very different from the effects on the other three arrhythmia models.

Antiarrhythmic Plasma Concentrations of Cibenzoline on Canine Ventricular Arrhythmias

Using two-stage coronary ligation-, digitalis-, and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of cibenzoline were examined and the minimum effective plasma concentration for each arrhythmia model was determined. Cibenzoline suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and adrenaline were 1.9 +/- 0.9 (by 8 mg/kg i.v.), 1.6 +/- 0.5 (by 8 mg/kg i.v.), 0.6 +/- 0.2 (by 2 mg/kg i.v.), and 3.5 +/- 1.3 (by 5 mg/kg i.v.) micrograms/ml, respectively (mean +/- SDM, n = 6-7). The concentration for adrenaline-induced arrhythmia was significantly higher than those for the other types of arrhythmias. This pharmacological profile is similar to those of mexiletine and tocainide, and all three drugs have central nervous system (CNS) stimulant action. Because cibenzoline had only weak hypotensive and sinus node depressive effects and was found to be orally active when given to coronary ligation arrhythmia dogs, its clinical usefulness is expected.

Effects of OPC-8212, a new positive inotropic agent, on canine ventricular arrhythmias.

OPC-8212, a positive inotropic agent that increases intracellular cyclic AMP and stimulates the Ca current, was compared with amrinone and AR-L 115 in their effects on canine ventricular arrhythmias. OPC-8212, up to 3 mg kg-1, did not worsen 24 h coronary ligation arrhythmias, while it aggravated ventricular arrhythmias seen 48 h after coronary ligation. However, OPC-8212 did not at any time induce ventricular fibrillation in dogs subjected to coronary ligation. OPC-8212, up to 3 mg kg-1, had no arrhythmogenic or antiarrhythmic effect on digitalis-induced arrhythmias, while amrinone and AR-L 115 showed antiarrhythmic effects. With adrenaline-induced arrhythmias, the three drugs aggravated ventricular tachycardia to produce ventricular fibrillation. The absence of a worsening effect of the new positive inotropic agents on digitalis arrhythmia may be helpful in clinical setting of combined therapy of these new drugs with digitalis.

Canine digitalis arrhythmia as a model for detecting Na-channel blocking antiarrhythmic drugs: A comparative study using other canine arrhythmia models and the new antiarrhythmic drugs, propafenone, tocainide, and SUN 1165

Antiarrhythmic effects of three new drugs, propafenone, tocainide, and SUN 1165, were examined using three canine ventricular arrhythmia models, i.e., digitalis, adrenaline and two-stage coronary ligation arrhythmias. The effects of procainamide, disopyramide, lidocaine, and phenytoin, class 1 antiarrhythmic drugs, on digitalis arrhythmia were also examined. The minimum effective plasma concentrations of all these drugs for each arrhythmia model were determined for a quantitative comparison. Propafenone and tocainide suppressed all the arrhythmias, while SUN 1165 suppressed digitalis and coronary ligation arrhythmias. The minimum effective plasma concentrations of propafenone for digitalis, adrenaline, 24-h coronary ligation, and 48-h coronary ligation arrhythmias were 1.8 +/- 0.7, 0.58 +/- 0.20, 3.5 +/- 0.3, and 3.6 +/- 0.9 micrograms/ml, respectively, and those of tocainide were 6.2 +/- 2.1, 23.7 +/- 9.0, 11.4 +/- 0.5, and 8.6 +/- 2.9 micrograms/ml, respectively (mean +/- standard deviation, n = 6-7). The minimum effective concentrations of SUN 1165 for digitalis, 24-h coronary ligation, and 48-h coronary ligation arrhythmias were 0.92 +/- 0.19, 2.5 +/- 0.4, and 1.2 +/- 0.4 micrograms/ml. The minimum effective concentrations for digitalis arrhythmias were 1.7 +/- 0.4 micrograms/ml for disopyramide, 10.1 +/- 2.4 micrograms/ml for procainamide, 3.5 +/- 1.6 micrograms/ml for lidocaine, and 11.3 +/- 3.0 micrograms/ml for phenytoin. Digitalis arrhythmia seems to be a useful model for detecting class 1 drugs, as it was suppressed by all the class 1 Na-channel blocking antiarrhythmic drugs, while class 2 beta adrenergic blockers and class 4 Ca-channel blockers had no effect. Also, not all the class 1 drugs suppressed coronary ligation and adrenaline arrhythmias.

The effect of aspirin, indomethacin and sodium meclofenamate on coronary artery ligation arrhythmias in anaesthetized rats

The intravenous administration of either aspirin, (in doses of 1 and 3 mg/kg) sodium meclofenamate (1 and 3 mg/kg) or indomethacin (1 and 3 mg/kg) markedly reduced ventricular arrhythmias (VT and VF) induced by coronary artery ligation in anaesthetised rats. Their effect were very pronounced on ventricular ectopic activity occuring between the sixteenth and thirtieth min. These effects suggest the desirability of combining the non steroidal antiy-inflammatory drugs with β-madrenergic blockers in the treatment of ventricular arrhythmias following acute myocardial infarction.

Quantitative analysis of the antiarrhythmic effect of drugs on canine ventricular arrhythmias by the determination of minimum effective plasma concentrations.

Antiarrhythmic effects and minimum antiarrhythmic plasma concentrations (min PC) were examined using three canine ventricular arrhythmia models, i.e., two-stage coronary ligation arrhythmia (Cor), halothane-adrenaline arrhythmia (Adr) and digitalis arrhythmia (Dig). Disopyramide suppressed these three arrhythmias and its min PCs were 5.3 +/- 1.8 (Cor), 4.2 +/- 1.1 (Adr) and 1.7 +/- 0.4 micrograms/ml (Dig). Procainamide suppressed coronary ligation arrhythmia and its min PC was 27.1 +/- 4.0 micrograms/ml, but was not effective on adrenaline arrhythmia. Aprindine was effective on three arrhythmias and its min PCs were 1.6 +/- 0.3 (Cor), 1.0 +/- 0.4 (Adr) and 0.8 +/- 0.4 micrograms/ml (Dig). Lidocaine was not effective on coronary ligation arrhythmia, but was effective on adrenaline arrhythmia and its min PC was 15 micrograms/ml. Phenytoin was effective on three arrhythmias and its min PCs were 9.8 +/- 2.0 (Cor), 12.1 +/- 3.1 (Adr) and 11.3 +/- 3.0 micrograms/ml (Dig). It was not specifically effective on canine digitalis arrhythmia. Propranolol and other beta-blockers were effective on adrenaline arrhythmia, but very high doses were necessary for suppressing coronary ligation and digitalis arrhythmias. Verapamil was only effective on adrenaline arrhythmia and its min PC was 0.03 +/- 0.01 microgram/ml. Canine min PCs of drugs were almost the same as those reported in man except for procainamide and lidocaine. Membrane stabilizing effects seem to be important for suppressing canine ventricular arrhythmias.

EFFECTS OF PROSTAGLANDINS ON LATE CORONARY LIGATION ARRHYTHMIAS IN THE DOG

Effects of an intravenous injection of indomethacin, prostaglandins (PGs) E1, E2 and F2α and prostacyclin were examined by the use of a model of two-stage coronary ligation arrhythmias in conscious dogs. Indomethacin had no effect on the arrhythmias occurring 48 hr after coronary ligation. PGs and prostacyclin were injected after the injection of indomethacin. PGs did not show any significant antiarrhythmic effects on the/arrhythmias occurring 48 hr after coronary ligation, while prostacyclin showed a transient arrhythmogenic effect. From the foregoing results, both endogenous and exogenous PGs do not seem to play a significant role in the genesis of late coronary ligation arrhythmias in the dog.

Effects of prostaglandins on late coronary ligation arrhythmias in the dog.

Effects of an intravenous injection of indomethacin, prostaglandins (PGs) E1, E2 and F2 alpha and prostacyclin were examined by the use of a model of two-stage coronary ligation arrhythmias in conscious dogs. Indomethacin had no effect on the arrhythmias occurring 48 hr after coronary ligation. PGs and prostacyclin were injected after the injection of indomethacin. PGs did not show any significant antiarrhythmic effects on the arrhythmias occurring 48 hr after coronary ligation, while prostacyclin showed a transient arrhythmogenic effect. From the foregoing results, both endogenous and exogenous PGs do not seem to play a significant role in the genesis of late coronary ligation arrhythmias in the dog.