Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiac electrophysiologic actions of a novel calcium antagonist, KB-944 [Fostedil, Abbott-53986, diethyl 4-(benzothiazol-2-yl) benzylphosphonate], were examined in anesthetized dogs. Cumulative doses of 0.5, 2.5 and 12.5 mg/kg i.v. produced dose-dependent increases in atrioventricular (AV) nodal refractoriness and conduction time (AH interval), although failing to alter atrial or ventricular refractoriness. Intra-atrial, infranodal and intraventricular conduction (PA, HV and H-EG intervals, respectively) were unchanged. In three of nine dogs, 2.5 to 12.5 mg/kg of KB-944 produced third degree AV blockade. Pretreatment with propranolol (0.1 mg/kg) was accompanied by sinoatrial blockade in three of five dogs who later received 12.5 mg/kg of KB-944. Glucagon (4 micrograms/kg) reversed the electrophysiologic changes associated with administration of KB-944 alone or in conjunction with propranolol. An examination of the temporal profiles of the cardiac electrophysiologic effects of KB-944 indicated selective alterations in AV nodal conduction and refractoriness for durations of approximately 60, 120 and 180 to 240 min after administration of 0.3, 1.0 or 3.0 mg/kg i.v. These results suggest that KB-944 may be an effective agent for treatment of supraventricular tachyarrhythmias via selective depression of the AV nodal conduction system.
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PMID:Cardiac electrophysiologic actions of KB-944 (Fostedil), a new calcium antagonist, in the anesthetized dog. 654 Aug 6

The electrophysiologic effects of incremental doses of intravenous amiodarone were studied in the intact neonatal canine heart and were compared with the responses observed in the adult. Seven neonatal puppies aged 5 to 14 days, and 6 adult dogs were studied. Assessment of sinus and atrioventricular (AV) nodal function and atrial and ventricular refractory periods was performed using standard His bundle recording techniques and programmed extrastimulation before and after doses of 2.5, 5 and 10 mg/kg of intravenous amiodarone. Amiodarone depressed sinus node cycle length, sinus node recovery time and AV nodal conduction in both groups. Atrial and ventricular refractory periods were also prolonged in a dose-dependent fashion in both the neonatal and adult dogs. Although similar responses to amiodarone were observed in both groups, the immature dogs were more sensitive to amiodarone in prolongation of atrial refractory periods and depression of sinus node recovery time. The neonatal group, however, demonstrated more resistance to amiodarone-induced depression of AV nodal conduction. Thus, intravenous amiodarone produces dose-dependent electrophysiologic changes in the neonate similar to those in the adult, although the significant differences in drug sensitivity may be clinically important.
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PMID:Dose-dependent electrophysiologic effects of amiodarone in the immature canine heart. 661 89

To ascertain whether the long cardiac pauses on the Holter ECGs of patients with the sick sinus syndrome were related to the spontaneously occurring overdrive suppression, the heart rates for the 12 seconds preceding the cardiac pauses longer than 5 seconds were compared with that averaged for 24 hours. Even in six out of seven patients with bradycardia-tachycardia syndrome the former rate was not significantly greater than the latter, indicating that episodes of such long cardiac pauses may not result from spontaneously occurring overdrive suppression. This observation was also consistent with the result that no statistically significant correlation was obtained between the maximum pauses measured from Holter ECGs of sick sinus syndrome and those obtained by the overdrive suppression test. In conclusion, many episodes of long life-threatening cardiac pauses observed in sick sinus syndrome may be attributed to accidental depression of the sinus nodal and subsidiary pacemaker activity rather than to spontaneously occurring overdrive suppression; therefore, Holter monitoring may be useful as an additional tool for diagnosis of sick sinus syndrome.
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PMID:Comparative evaluation of depressed automaticity in sick sinus syndrome by Holter monitoring and overdrive suppression test. 668 81

Electrophysiologic and hemodynamic studies were performed before and after intravenous infusion of a new antiarrhythmic agent, propafenone, in 28 patients with recurrent ventricular tachycardia. Propafenone was given at a loading dose of 2 mg/kg in all patients. Subsequently, group A, the first 14 patients, received 1 mg/min and group B, the second 14 patients, received 2 mg/min continuous infusion. Propafenone exerted no effect on sinus nodal recovery time and sinoatrial conduction time, but significantly prolonged atrioventricular (AV) nodal and His-Purkinje conduction time and the QRS duration (respectively, 95 +/- 19, 48 +/- 10 and 120 +/- 23 ms before, and 110 +/- 28, 53 +/- 10 and 135 +/- 27 ms after; p less than 0.001). Propafenone did not change the mean arterial blood pressure but slightly increased right atrial, pulmonary artery and capillary wedge pressures resulting in mild depression of the cardiac index (2.6 +/- 0.8 liters/min per m2 before and 2.3 +/- 0.7 liters/min per m2 after; p less than 0.001). None of the patients were symptomatic from these changes. In group A, propafenone did not affect the inducibility of ventricular tachycardia except for one patient whose arrhythmia was sustained before and become nonsustained after propafenone. In group B, sustained ventricular tachycardia became noninducible in three patients and nonsustained in two patients, and nonsustained ventricular tachycardia became noninducible in one patient after propafenone. Therefore, an appropriate loading dose of intravenous propafenone such as 2 mg/kg followed by 2 mg/min infusion may be given safely and may suppress ventricular tachycardia. Propafenone may be a useful addition to currently available antiarrhythmic agents.
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PMID:Electrophysiologic and hemodynamic effects of intravenous propafenone in patients with recurrent ventricular tachycardia. 670 82

The effect of alinidine on transmembrane electrical activity of nodal and atrial fibers was studied in the isolated right auricle of the guinea-pig. Alinidine was applied in concentrations between 0.72 and 28.5 X 10(-5) M. In nodal fibers the main effect was a dose-dependent decrease in rate of diastolic depolarization and a delayed repolarization of especially the terminal part of the action potential. In both fiber types alinidine causes a marked delay of the terminal part of repolarization; the increase of the duration of the action potential was related to the alinidine concentration over the whole concentration range used. In addition the amplitude of the action potential and the maximal diastolic potential are increased dose dependently up to a concentration of 2.8 x 10(-5) M. Application of higher concentrations does not increase these parameters. In nodal fibers diastolic depolarization is already depressed considerably at a relatively low concentration. This is particularly so in fibers that normally have a high rate of diastolic depolarization, i.e., the dominant pacemaker fibers. A shifting of the pacemaker seems only to occur at high concentrations (11.4 X 10(-5) M or higher). The strong negative chronotropic effect of alinidine can be attributed to both the depression of diastolic depolarization and the increase in duration of the action potential. At low concentrations the increase of the maximum diastolic potential can also contribute to the slowing of the heart rate.
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PMID:Electrophysiological effects of alinidine on nodal and atrial fibers in the guinea-pig heart. 671 76

In 13 patients with chronic atrial fibrillation, programmed right ventricular pacing was performed before and after intravenous administration of 4 mg gallopamil. Application of the Ca-antagonist resulted in a marked decrease in the ventricular response in all and in a regularization of the ventricular response (variation coefficient of the ventricular cycle length: less than 10%) in 7 of 13 cases, while atrial fibrillation persisted. During regularization right ventricular extrastimulus testing showed a constancy of the postextrasystolic interval irrespective of the changes in the coupling interval of the extrasystole. The postextrasystolic cycle was slightly longer than the basic cycle; the difference amounts to a mean value of 107 +/- 22 ms. During the control period the postextrasystolic cycle showed the same irregularity as the basic cycle. The same random distribution was observed if the first 10 cycles of the spontaneous rhythm were analyzed after a short period of ventricular overdrive pacing. After regularization the first 2-3 postpacing cycles were markedly prolonged, and during the following cycles a gradual adjustment to the length of the basic cycles before overdrive pacing was seen, resembling the warming up of a pacemaker. It is concluded that regularization is most probably due to atrioventricular nodal depression and the occurrence of a junctional escape pacemaker.
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PMID:[Regularization of ventricular intervals in atrial fibrillation--electrophysiologic findings on the underlying mechanism]. 671 83

The electrophysiologic changes produced by the intravenous administration of 0.6 mg/kg of sotalol were studied in 12 patients aged 45 to 85 years (mean 68 years). Effects upon atrioventricular (AV) nodal conduction time (AH interval) and His-Purkinje conduction time (HV interval) were assessed at identical rates. The Wenckebach cycle length was determined by rapid atrial stimulation. Refractory periods before and after the drug were compared at the same cycle length. Retrograde conduction was studied, with special reference to reentry phenomena within the His-Purkinje system. Sinoatrial function was evaluated using sinus node recovery time and sinoatrial conduction time. The following changes were noted: (1) decrease in sinus rate, (2) prolongation of QT interval, (3) depression of AV nodal conduction (prolonged AH interval) and increase in effective and functional refractory periods of the AV node, (4) increase in relative refractory period of the His-Purkinje system with no associated change in HV interval, (5) prolongation of effective refractory period in the atrium and ventricle, and (6) increase in retrograde refractory period of specialized ventricular tissue and depressed conduction of premature ventricular responses. Reentry phenomena in the His-Purkinje system were not significantly affected by the drug. Thus certain of the electrophysiologic effects of sotalol in humans were found to be in favor of a class III antiarrhythmic mechanism of action. These results justify further studies to evaluate the usefulness of this drug as an antiarrhythmic agent.
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PMID:Clinical electrophysiology of intravenous sotalol, a beta-blocking drug with class III antiarrhythmic properties. 672 May 18

Amiodarone, a wide spectrum antiarrhythmic agent, has been associated with hypotensive reactions in man as well as in dogs after intravenous use. This hypotensive effect has been attributed to Tween 80, the diluent in the commercially available form of amiodarone. We studied the electrophysiologic effects of Tween 80 in the cardiac conduction system of the dog. Electrophysiologic studies were conducted in anesthetized adult dogs before and after the administration of 10 and 20 mg/kg of Tween 80, equivalent to the amount of diluent in 5 and 10 mg/kg respectively of commercial intravenous amiodarone. In addition to a drop of 60% in systolic blood pressure and 66% in diastolic blood pressure (p less than 0.005), 10 mg/kg of Tween 80 induced a decrease in heart rate (sinus cycle length increased from 523 +/- 57 msec to 662 +/- 27 msec, p less than 0.025), prolongation of sinus node recovery time (652 +/- 77 msec to 804 +/- 45 msec, p less than 0.05), depression of AV nodal function manifested by induction of Wenckebach at longer cycle length (from 208 +/- 18 msec to 266 +/- 14 msec, p less than 0.005), and increase in atrial ERP (from 138 +/- 7 msec to 176 +/- 14 msec, p less than 0.025) and FRP (from 180 +/- 14 msec to 209 +/- 12 msec, p less than 0.025). No further significant changes were observed after the second Tween 80 dose. The ventricular ERP increased significantly (from 168 +/- 18 msec to 20 +/- 16 msec, p less than 0.025) following the 20 mg/kg dose. It is demonstrated that Tween 80 is a potent depressant of the cardiac conduction system in the dog, capable of causing electrophysiologic changes similar to those produced by amiodarone in humans and dogs.
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PMID:Electrophysiologic effects of Tween 80 in the myocardium and specialized conduction system of the canine heart. 673 37

Verapamil hydrochloride, a prototype calcium antagonist, is now marketed in the United States for the acute treatment of supraventricular tachyarrhythmias and for chronic management of vasospastic and chronic stable angina. It inhibits the slow inward channel in in the heart and blocks calcium influx in smooth muscle. Its intrinsic negative inotropic action, which is apparent in isolated tissues, is offset in vivo by peripheral vasodilation. It has a mild, noncompetitive sympathetic antagonist effect; its most important electrophysiologic action is a depression of AV nodal conduction, accounting for its effect in supraventricular tachyarrhythmias. Its hemodynamic actions are characterized by a complex interplay of changes in preload, afterload, contractility, heart rate, and coronary blood flow. It does not depress cardiac function, except in severe heart failure. The drug has a mild dilator action on coronary arteries and reverses ergonovine-induced vasoconstriction. Controlled trials have established its role in Prinzmetal's variant angina, unstable angina, and chronic stable angina. It has also been found to be effective in obstructive cardiomyopathies. The potential role of verapamil in such conditions as hypertension, cardioprotection, and Raynaud's phenomenon needs further evaluation; at present these indications have not been approved by the Food and Drug Administration. The most common side effects include constipation, skin rash, and dizziness; AV block, heart failure, and sinus arrest may occasionally be encountered, especially when ventricular function is compromised or conduction system disease is present.
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PMID:Verapamil hydrochloride: pharmacological properties and role in cardiovascular therapeutics. 676 30

The electrophysiological effects of diltiazem (0.25 mg/kg), administered by intravenous bolus, have been assessed during intracardiac investigation in 10 patients. Effects on both sinus node and atrioventricular nodal function were measured, as was the influence on reentry atrioventricular tachycardia. There was a tendency for the sinus rate to increase after both diltiazem and verapamil, although with neither drug was this uniform. There was, however, a consistent depression of atrioventricular nodal function with diltiazem which was similar in magnitude to the changes seen after verapamil. With neither drug was there an alteration in His-Purkinje conduction. The drugs had similar effects when given during reentry tachycardia. In six of eight patients, termination occurred, whereas, in the others, both drugs slowed the arrhythmia but failed to terminate it. Diltiazem shows a range of electrophysiological and antiarrhythmic properties similar to those of verapamil. These make it potentially useful for both the acute and chronic treatment of arrhythmias where depression of atrioventricular nodal function is desired.
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PMID:The comparative effects of diltiazem and verapamil on atrioventricular conduction and atrioventricular reentry tachycardia. 683 49


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