Number Of Ventricular Ectopic Beats Research Articles

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.

Ketanserin and Ritanserin Can Reduce Reperfusion-Induced But Not Ischaemia-Induced Arrhythmias in Anaesthetised Rats

The effects of the 5-hydroxytryptamine2 (5-HT2) antagonists ketanserin and ritanserin on ischaemia- and reperfusion-induced arrhythmias were investigated in pentobarbitone-anaesthetised rats. Both ketanserin (3 mg kg-1) and ritanserin (1 mg kg-1) significantly reduced the incidence of ventricular fibrillation (from 60 to 25% and 88 to 12%, respectively) and the mortality induced by reperfusion after 5 min of myocardial ischaemia. Neither drug significantly altered the number of ventricular ectopic beats, the incidence of ventricular tachycardia, ventricular fibrillation, or mortality during the first 25 min of coronary artery occlusion. Significant dose-dependent reductions in heart rate and arterial blood pressure were observed with all doses of ketanserin (0.1-3 mg kg-1) and ritanserin (0.3 and 1 mg kg-1), but neither drug had any major effect on arterial blood gases or pH. In isolated guinea pig and rat atria and ventricular muscle preparations, ketanserin (10(-5) M) and ritanserin (3 X 10(-5) M) reduced the maximal driving frequency, whereas 5-HT itself was without effect. The results suggest that the antiarrhythmic activity of ketanserin and ritanserin observed in this study was probably not due to 5-HT2 receptor or alpha 1-adrenoceptor blockade, but may have been due to a direct action on cardiac muscle.

Antiarrhythmic effects of the thromboxane antagonist BM 13.177

The effects of the thromboxane antagonist BM 13.177 (5 mg kg −1 + 0.15 mg kg −1 min −) was investigated on the ventricular arrhythmias that result from coronary artery occlusion and reperfusion in anaesthetised open-chest greyhounds. BM 13.177 markedly reduced the severity and incidence of arrhythmias resulting from ischaemia; the number of ventricular ectopic beats was reduced from 1 084 ± 159 (in controls) to 544 ± 179 (in dogs given BM 13.177) and the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) were reduced from 86 to 22% and from 30 to 10% respectively. Following reperfusion the incidence of VF was 86% in controls and 44% in dogs given BM 13.177. Thus the total incidence of VF during the combined ischaemia-reperfusion insult was significantly reduced by treatment with BM 13.177 from 90% (in control dogs) to 50%. These results lend further support to the hypothesis that thromboxane is involved in the genesis of arrhythmias and that blockade of thromboxane receptors may be a suitable approach to antiarrhythmic therapy under conditions of ischaemia and reperfusion.

Effects of bunazosin and propranolol on ventricular arrhythmias in dogs with hypokalemia

The arrhythmogenic mechanism in dogs with hypokalemia was investigated in relation to the effects of an alpha 1-blocking agent and a beta-blocking agent. Hypokalemia was induced by inserting an ion-exchange resin into the colon. In the hypokalemia group, nine out of 17 dogs with arrhythmia ratios of over 10% (that is the percentage of the number of ventricular ectopic beats divided by the total number of heart beats during 5 min, after 10 micrograms/kg of epinephrine injection) were observed. In the control group (n = 13), which maintained normal serum K+ levels, only one dog showed an arrhythmia ratio of over 10%. Dogs with lower serum K+ levels showed higher arrhythmia ratios. The Ca2+ content of heart mitochondria, considered to be a reflection of intracellular Ca2+ concentration, was 24.4 +/- 5.7 nmoles/mg protein in the control group 5 min after epinephrine injection, while that of the hypokalemia group was increased to 35.0 +/- 13.4. A good reciprocal correlation between the concentration of serum K+ just before epinephrine injection and mitochondrial Ca2+ content was observed in the hypokalemia group (r = -0.79), while in the control group, no correlation was observed. Clear correlation between mitochondrial Ca2+ content and the arrhythmia ratio was also observed in the propranolol group. Pretreatment with bunazosin, an alpha 1-"blocker," effectively prevented the increase in mitochondrial Ca2+ content, and reduced the arrhythmia ratio. On the other hand, pretreatment with propranolol, a beta-"blocker," did not affect the mitochondrial Ca2+ content and the arrhythmia ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of cardiac arrhythmias induced by epinephrine in dogs with hypokalemia

To investigate the mechanism of ventricular arrhythmias induced by epinephrine in dogs with hypokalemia, 30 adult mongrel dogs were separated into a control group (n = 13) and a hypokalemia group (n = 17). In the hypokalemia group, sodium polystyrene sulfonate (5 g/kg body weight) was infused into the colon. In both groups, the serum concentrations of sodium, potassium and calcium were measured every 15 minutes for 60 minutes. The mean (+/- standard deviation) serum potassium level of the hypokalemia group decreased significantly from 3.81 +/- 0.21 to 2.92 +/- 0.36 mEq/liter; there were no significant changes in other electrolytes. After 60 minutes, epinephrine (10 micrograms/kg) was injected intravenously in the hypokalemia and control groups, and the arrhythmia ratio (the number of ventricular ectopic beats divided by the total heart rate) was calculated for 5 minutes. Each group was further classified into subgroups of dogs with an arrhythmia ratio higher or lower than 10%. An arrhythmia ratio over 10% was observed in 7.7% of the control group and 53% of the hypokalemia group. Immediately after 5 minutes of epinephrine injection, myocardial mitochondria and plasma membrane fraction were prepared from each group. Mitochondrial calcium content and phospholipase activity of plasma membrane fraction were determined. Significant increases in both mitochondrial calcium content and phospholipase activity were observed in the dogs with hypokalemia and an arrhythmia ratio greater than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereospecific antiarrhythmic effect of opioid receptor antagonists in myocardial ischaemia.

The effects of the stereoisomers of two different antagonists at opioid receptors were examined on the ventricular arrhythmias that result from acute coronary artery ligation in anaesthetized male rats. (-)-Mr 1452(but not the (+)-isomer, Mr 1453) reduced, in a dose-dependent manner, the number of ventricular ectopic beats and the incidence or duration of both ventricular tachycardia and fibrillation. (-)-WIN 44,441-3 (but not its (+)-isomer, WIN 44,441-2) had a similar protective effect in ischaemia. These results suggest that antagonism of the effects of endogenous opioid peptides at specific receptors results in reduced severity of arrhythmias in myocardial ischaemia.

Effects of the enantiomers of the dihydropyridine derivative 202–791 on contractility, coronary flow and ischemia-related arrhythmias in rat heart

The (+)-enantiomer of the dihydropydine 202–791 produced coronary constrictor and positive inotropic effects in Langendorff-perfused rat hearts whereas (-)-202-791 showed coronary dilator and negative inotropic effects. Both enantiomers showed the vascular effects at lower concentrations than the myocardial effects. Furthermore, the (+)-enantiomer significantly increased whilst the (-)-enantiomer reduced the number of ventricular ectopic beats occurring during coronary ligation. Arrhythmia-enhancing effects must therfore be considered when the potential therapeutic uses of calcium channel activators are discussed.

Lidoflazine in the early stages of acute myocardial ischaemia.

1 Pretreatment of anaesthetized rats with intravenously administered lidoflazine (an antianginal agent) reduced the incidence and severity of ventricular arrhythmias which resulted from acute coronary artery ligation. Ventricular fibrillation was completely prevented by doses of 50 micrograms/kg and 2 mg/kg and no animal so treated died ( contrast 50% incidence of fibrillation in the controls and 30% mortality). 2 In anaesthetized greyhound dogs, lidoflazine (2 mg/kg) administration resulted in transient reductions in systemic arterial pressure, LV dP/dt max and cardiac output. Coronary sinus Po2 was markedly increased, indicating pronounced coronary vasodilatation. 3 Lidoflazine pretreatment inhibited the increase in epicardial ST-segment elevation which resulted, in dogs, from short (3 min) occlusions of the left anterior descending coronary artery. This effect was especially marked at sites where, in control occlusions, ST-segment elevation was most pronounced. 4 Lidoflazine greatly reduced the number of ventricular ectopic beats which usually resulted from more prolonged (30 min) periods of acute coronary artery occlusion. There was no ventricular fibrillation in these dogs (contrast 25% incidence in the controls). 5 Lidoflazine did not modify the ventricular fibrillation which results from reperfusion of a previously ischaemic area of the left ventricular wall.

Antiarrhythmic effects of Org 6001 in rats: correlation with plasma and tissue drug concentrations.

The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10, 20, 50 and 100 mg/kg given 1 h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0-30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug.

The effects of prostaglandins E2, F2 alpha, prostacyclin, flurbiprofen and aspirin on arrhythmias resulting from coronary artery ligation in anaesthetized rats.

1 Various prostaglandins and inhibitors of prostaglandin synthesis were administered prior to acute coronary artery ligation in anaesthetized rats and their effects were assessed on the number and severity of the resulting early arrhythmias (ventricular ectopic activity; incidence and duration of ventricular tachycardia and of ventricular fibrillation). 2 Prostaglandin E2 (PGE2), PGF2 alpha and prostacyclin all showed antiarrhythmic activity; in contrast flurbiprofen increased the incidence of ventricular fibrillation and mortality. 3 Both the number of ventricular ectopic beats and the incidence of ventricular fibrillation were reduced by aspirin. 4 The results suggest that the release of endogenous PGE2, PGF2 alpha and prostacyclin could reduce early post-infarction ventricular arrhythmias whilst the protective effect of aspirin in this model adds further support for the hypothesis that thromboxane release is involved in the genesis of these arrhythmias.

A prospective randomized trial of tocainide in patients following myocardial infarction

One hundred forty-six patients with recent acute myocardial infarction were grouped at random into those treated with tocainide, an oral analogue of lignocaine, or placebo and followed up for 6 months. In addition to standard investigations, a 24-hour ambulatory taped ECG recording was obtained prior to randomization and thereafter at 2, 8, 16, and 24 hours after discharge. The ECGs were analyzed by means of an automated, computerized reporting system. Forty-two patients had significant ventricular arrhythmias, 10 of whom had effective plasma levels of tocainide compared with 27 patients on placebo ( P < 0.005). In the placebo patients with increasing mobilization there was a consistent rise in the number of ventricular ectopic beats per day. There was no such increase in the tocainide patients ( p < 0.01). Side effects were few and the incidence of central nervous system side effects was similar in both the tocainide and placebo groups. There was no conclusive evidence of myocardial depression, heart rate and blood pressure being unchanged over the 6-month period. Although ventricular arrhythmias were suppressed, the number of patients in the study was too small to draw conclusions regarding the mortality rate.

The influence of prostacyclin on coronary occlusion induced arrhythmia in cats

The present study examined the effect of prostacyclin (PGI2) on ventricular arrhythmias following coronary artery occlusion in the cat. The left anterior descending coronary artery (LAD) was occluded abruptly in 50 cats anesthetized with a-chloralose.The ECG (Lead II) along with arterial blood pressure were monitored before and for at least one hour after occlusion. Either vehicle or PGI2 was infused at a rate of 0.15 ml·min 1 into the left atrium 15 min before and 1 hour after LAD occlusion. PGI2 was infused at 4 doses: 2.7,27,270 and 2700 pmole.kg 1·min 1. Infusion of PGI2 before occlusion produced a dose dependent decrease in mean arterial blood pressure with no significant change in heart rate. Abrupt occlusion of the LAD produced ventricular arrhythmia in all cats ranging from ventricular premature beats to ventricular fibrillation (VF). In cats infused with PGI2 the incidence of VF ranged from 30–40% at the low and middle doses to a maximum of 60% at the highest dose (2700 pmoles·kg 1·min 1). The incidence of VF in the latter group was two times greater than that observed in the control group (30%). In addition, the mean number of ventricular ectopic beats was greater at the 27 and 2700 pmole·kg 1·min 1 doses of PGI2 than in the control group. An increase in ventricular ectopic beats was not observed at the 2.7 or 270 pmole·kg 1·min 1 doses of PGI2. These data indicate that PGI2 can exert an arrhythmogenic effect following coronary artery occlusion and that this effect occurs in a biphasic manner i.e., the increase in arrhythmia observed at 27 did not occur at 270 but occurred again at the 10 fold higher dose (2700 pmole·kg 1·min 1).At the lowest dose of PGI2 infarct size was approximately 14% less than in the control group while, at the highest dose, infarct size was 20% greater than control and approximately 40% greather than the lowest dose of PGI2.

Kinetics of Hemodynamic and Electrocardiographic Changes Following Intravenous Disopyramide

Changes in hemodynamic and ECG variables following disopyramide (1.7 mg = 3.9 mmol/kg b.wt.) were studied in 9 patients with ventricular arrhythmias. All patients displayed a marked reduction in the number of ventricular ectopic beats, all except one exhibiting complete abolition of the arrhythmia for at least 30 min. QT and QRS intervals showed statistically significant prolongations, and thereafter decreased exponentially with time. Above a certain concentration threshold that varied between the patients, systolic time intervals and aortic (dp/dt)max showed linear changes with increasing drug serum levels. Changes in diastolic pulmonary artery pressure showed no simple relationship with disopyramide concentration or time after injection. In 3 out of 4 patients studied, there was a good correlation between the lowest level of disopyramide that elicited both an antiarrhythmic effect and a demonstrable decrease in cardiac contractility.

Antiarrhythmic and electrocardiographic effects of single oral doses of disopyramide

Ten patients with various heart diseases and ventricular arrhythmia received a single oral dose of disopyramide (DE) 200 mg. The ECG was recorded continuously for about 50 h from 2-4 h before drug administration. A statistically significant reduction in the number of ventricular ectopic beats (VEBs) was seen 1.0-3.5 h after drug intake; the average number of VEBs per 30 min decreased from 317 during the control period to 92 by 1.0-3.5 h after treatment and if one patient who did not respond is excluded, the corresponding figures were 272 and 14, respectively. Consecutive VEBs were seen in seven patients before DE was given and decreased significantly (p less than 0.05) 1.5-5.5 h after drug administration. There was no change in the PQ interval, the QRS interval showed a slight increase, whereas the QT interval was prolonged 0.5-4 h after administration of DE. A specific gas chromatographic method was used for DE assay in plasma and urine. Absorption was rapid in all patients. Urinary excretion during the first 48 h after drug intake varied between 35 and 75%. The lowest effective antiarrhythmic concentration estimated in six patients ranged from 1.4 to 7.0 mug/ml. beta-Phase half-life in five patients was between 10.3 and 22.1 h.

Relation between infarct size and ventricular arrhythmia.

In order to determine whether ventricular arrhythmia is quantitatively related to infarct size estimated enzymatically we studied 31 patients with acute myocardial infarction without cargiogenic shock. Infarct size index was estimated from hourly serum creatine kinase (CK) changes during periods of 48 to 72 hours. Ventricular arrhythmia was quantified by automated analysis of continuous electrocardiographic recordings over a period of 20 hours with the use of the Argus/H computer system. Patients were classified into three groups according to infarct size index. Patients in all groups had similar average heart rate, blood pressure, serum potassium, and arterial pH and PCO2 values during the first 10 hours after admission. The total number of ventricular ectopic beats (VEB), frequency of couplets, and ventricular tachycardia, and peak rate of ventricular ectopic beats during the first 10 hours after admission were all related to infarct size index. For example, patients with small, medium, and large estimated infarct size averaged 26, 104, and 405 ventricular ectopic beats, respectively. These results suggest that the severity of ventricular arrhythmia early after myocardial infarction is related to the extent of myocardial injury as estimated enzymatically. Thus the apparent efficacy and therefore the evaluation of antiarrhythmic agents early after myocardial infarction may be influenced by the magnitude of injury sustained by the heart.

Reduction in ventricular arrhythmias following acute coronary artery ligation in the dog after the administration of creatine phosphate.

The infusion of creatine phosphate into the left ventricle of dogs markedly reduced the number of ventricular ectopic beats which normally result from acute coronary ligation. This dose of creatine phosphate (100 mg/kg) had no significant effect on resting haemodynamics or on myocardial metabolism.

Treatment of refractory ventricular tachysystole with hyperbaric oxygenation

A case of acute myocardial infarction in a 37 year old man resulting in severe ventricular tachyarrhythmias is reported. The patient's course was altered for the better after two exposures to hyperbaric oxygenation, each lasting seven hours. Hyperbaric oxygenation appeared to be successful in reducing the ventricular rate and in abolishing the requirement for vasopressors; during the first period of exposure, when the patient was critically ill, the number of ventricular ectopic beats was reduced during hyperbaric oxygenation. This experience indicates the need for further experimental trials of hyperbaric oxygenation in the control of refractory ventricular arrhythmias due to myocardial infarction.