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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electrophysiologic effects of the new antiarrhythmic drug, propafenone, were evaluated in anesthetized closed-chest dogs and on isolated cardiac tissues with the microelectrode technique. Propafenone (2 to 4 mg/kg intravenously) had no effect on sinus rate or on sinus nodal recovery time, but caused a dose-dependent significant decrease in the rate of idioventricular rhythm and increased the duration of ventricular overdrive suppression in dogs (n = 8) with complete atrioventricular block. On isolated canine Purkinje fibers (n = 8) manifesting automaticity with resting membrane potential less negative than -70 mV, propafenone reduced the slope of phase 4 depolarization and reduced the rate of automatic impulse initiation in a concentration-dependent manner (10(-6) M-4.10(-5) M). At these concentrations, propafenone had no effect on rabbit sinus nodal automaticity (n = 8) or on sinoatrial conduction. However, significant depression of sinus nodal automaticity occurred with propafenone concentrations above 5.10(-6) M in the presence of cholinergic or complete autonomic blockade with atropine (10(-6) M) and propranolol (5.10(-5) M). Propafenone caused a concentration-dependent decrease in the disparity of Purkinje fiber-ventricular muscle action potential duration (APD), mainly by shortening Purkinje fiber APD. We conclude: that propafenone suppresses idioventricular rhythm in the intact dog, most likely by depressing Purkinje fiber automaticity; the depressant effect of propafenone on sinus nodal automaticity is evident only during cholinergic receptor blockade; and the antiarrhythmic properties of propafenone may include removal of APD disparity by selective shortening of Purkinje fiber and not of ventricular muscle APD.
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PMID:Effects of propafenone on sinus nodal and ventricular automaticity: in vitro and in vivo correlation. 356 44

The purpose of these experiments was to determine the frequency dependence of the effects of amiodarone and its active desethyl metabolite on slow-channel tissues. Intravenous amiodarone and desethylamiodarone (10 or 25 mg/kg) increased atrioventricular conduction time (AVCT) and refractory period (AVERP) in open-chest, chloralose-anesthetized dogs. Drug effects on AVCT and AVERP were greatly augmented by increasing atrial stimulation frequency. The frequency dependence of drug effects was quantified by studying the response of atrioventricular (AV) conduction to changes in coupling interval. Under control conditions, premature atrial stimulation increased AVCT with a time constant of 70 msec. In the presence of amiodarone and desethylamiodarone, a biexponential relationship between AVCT and coupling interval was observed. One component had a time constant similar to control, and a slower component with a time constant of about 1 sec appeared. Slow-channel action potentials produced in canine cardiac false tendons by elevated potassium (25 mM) and isoproterenol in vitro showed interval-dependent changes in Vmax with a time constant averaging 74 msec in the absence of amiodarone. In the presence of amiodarone, a slower recovery phase of Vmax with a time constant averaging 0.94 sec was observed. These results indicate that amiodarone and its metabolite produce heart rate-dependent changes in AV nodal function in vivo and suggest use-dependent calcium-channel blockade as a mechanism of this action. Amiodarone's rate-related effects on slow-channel properties should produce selective depression of supraventricular tachyarrhythmias involving rapid activation of the AV node.
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PMID:Frequency-dependent effects of amiodarone on atrioventricular nodal function and slow-channel action potentials: evidence for calcium channel-blocking activity. 360 27

In anesthetized dogs, it has already been shown that cibenzoline (4 mg/kg i.v.) possesses class 1 anti-arrhythmic properties. In this work, the cardiac electrophysiologic effects of cibenzoline (1 mg/kg i.v.) were studied before and after propranolol (0.2 mg/kg i.v.) treatment. Cibenzoline caused a slight tachycardia, a reduction of conduction velocity in the His-Purkinje system and in the ventricle, but no significant effects in the atria and the atrioventricular node were detected. On the contrary, when dogs were given the beta-adrenoceptor blocking agent propranolol, cibenzoline produced major effects in the slow response structures, especially in the sinus node and the atrioventricular node (bradycardia and depression of the atrioventricular nodal conduction). No further effects were observed on the His-Purkinje system and ventricle as compared to administration of cibenzoline alone. In dogs, cibenzoline given i.v., had no effects on the slow response systems, probably because of sympathetic nervous system intervention since the class 4 effects of cibenzoline appeared after beta-adrenoceptor blockade.
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PMID:Evidence for a class 4 effect of cibenzoline "in vivo". 363 39

The effects of quinidine on sinus nodal and A-V nodal function were assessed in 20 patients (age: 60 +/- 7 years) with sinus bradycardia and a prolonged A-H interval. Electrophysiological studies were performed twice in each patient. In the first study, the measurements of sinus and A-V node function were evaluated both in the basal state and after autonomic blockade (propranolol 0.2 mg kg-1 and atropine 0.04 mg kg-1). Oral quinidine was administered for 3-4 days (1200 mg day-1) and the study was then repeated using the same methods. Comparison of data obtained in the two studies in the basal state allowed us to evaluate the overall effect of quinidine. Comparing the results obtained following autonomic blockade, the direct action of the drug could be assessed. In the basal state quinidine did not significantly change the function of either node. In contrast, after autonomic blockade, significant changes were noted after quinidine. In 3 patients with sinus rate less than 50 beats min-1 and an abnormal intrinsic heart rate, quinidine induced marked depression of sinus automaticity. These data suggest that: (1) in patients with sinus bradycardia and prolongation of the A-H interval, oral quinidine has a direct depressant effect on sinus and A-V nodal function, but this effect is counteracted by autonomically mediated actions; (2) in patients with moderate or severe bradycardia and an abnormal intrinsic heart rate, the drug can induce marked depression of sinus automaticity.
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PMID:Electrophysiological effects and mechanism of action of oral quinidine in patients with sinus bradycardia and first degree A-V nodal block. 367 37

The effects of 1.2, 1.7, and 2.3 MAC enflurane (ENF), halothane (HAL), and isoflurane (ISO) on specialized atrioventricular (AV) conduction times were compared with awake (control) in 23 dogs that were chronically instrumented for His bundle studies. Compared with awake, 1.2 MAC ENF and HAL produced 17% and 18% increases in AV nodal conduction time, respectively. There was little added prolongation related to depth of ENF or HAL. ISO did not prolong AV nodal conduction compared with awake at 1.7 (9%) and 2.3 MAC (12%). All agents produced an approximate 5% increase in His-Purkinje and ventricular conduction times compared with awake, with little additional effect related to depth of anesthesia. In separate experiments in ten of these dogs, anesthetic effects on conduction were determined following combined autonomic blockade with atropine and propranolol. During autonomic blockade, there was no effect of any anesthetic compared with awake, or to increased level of anesthesia, on specialized AV conduction times. The authors conclude that of the major inhalation anesthetics in current clinical use, ISO is least depressant of and ENF and HAL about equally depressant of AV nodal and His-Purkinje conduction times. Furthermore, depression of AV nodal conduction appears to be an indirect rather than direct effect of anesthesia. Finally, most depression of conduction occurs with light anesthesia, with little added depression related to depth of anesthesia over levels likely to be encountered clinically.
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PMID:Conscious-state comparisons of the effects of inhalation anesthetics on specialized atrioventricular conduction times in dogs. 371 34

High blood concentrations of local anesthetics are cardiotoxic. The aim of this study was to compare the effects of lidocaine and bupivacaine on the intrinsic pacemaker activity of in vitro sinoatrial nodal cells of the adult and neonatal guinea pig in the presence and absence of hypoxia and acidosis. Fifteen pairs of adult (greater than 80 days old) and neonatal (0-3 days old) hearts were isolated. Nodal tissues were suffused with Krebs-Ringer solution at 37 degrees C and exposed to increasing concentrations of either lidocaine (0.05-0.8 mM) or bupivacaine (0.01-0.4 mM). The suffusate was equilibrated either with 5% CO2, 95% O2 (pH 7.40, PO2 482 torr) or with 12% CO2, 88% N2 (pH 7.01, PO2 58 torr). Transmembrane action potentials were recorded from sinoatrial nodal cells and impulse intervals were converted to rates. We found that hypoxia and acidosis alone reduced rates in both adults and neonates, and that the reduction was additive to the effects of local anesthetics. Bupivacaine was 4-5 times more potent in decreasing rates than was lidocaine in both age groups. Lidocaine was about twice as effective in depressing neonatal rates as adult rates, and bupivacaine caused cessation of pacemaker activity in a greater percentage of nodes than did lidocaine. Our results demonstrate, in vitro, that the neonatal sinoatrial node is more sensitive to lidocaine and bupivacaine than is the adult node, that bupivacaine is more potent in depressing and stopping nodal activity, and that hypoxia and acidosis enhance pacemaker depression caused by these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of lidocaine and bupivacaine depression of sinoatrial nodal activity during hypoxia and acidosis in adult and neonatal guinea pigs. 374 Apr 90

Postganglionic stimulation of vagal terminals (PGVS) in the isolated rabbit heart atrioventricular (AV) node was used to study the effects of cholinergic influence on AV nodal conduction. Standard microelectrode techniques were used to record action potentials, predominantly from cells located in the N region of the AV node. In addition, programmed stimulation was used in conjunction with PGVS to initiate or terminate AVN reentry. The introduction of a single short burst of PGVS (total duration 50 to 100 msec, impulse duration 1 msec, and interimpulse interval 6 msec) with subthreshold amplitude for AV node fibers caused reproducible disorganization of the prevailing excitation front. This was manifest as local nonuniform depression of conduction, hump formations in the action potentials, and alteration in the sequence of depolarization. The introduction of repetitive bursts of PGVS revealed a triphasic time course of changes in AV nodal conduction time, representing initial maximal prolongation, relative shortening, and secondary inhibition. It was found that these phases corresponded to vagally induced initial disorganization and a subsequent rebound process. Vagally induced disorganization of the sequence of action potential depolarization was also a triggering mechanism for concealed as well as manifest AV nodal reentry. In the latter case the reentry circuit usually involved the AN region and perinodal atrial tissue. PGVS-induced depression of the N region was also able to block the retrograde wavefront, thereby terminating reentry. The possible relationship of PGVS-induced disorganization of conduction and the inhomogeneous structure of AV node are discussed. The present results provide additional information for better understanding of the AV nodal conduction abnormalities observed clinically and particularly those related to AV node-vagus interaction.
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PMID:Effect of postganglionic vagal stimulation on the organization of atrioventricular nodal conduction in isolated rabbit heart tissue. 375 95

The electrophysiologic effects of intravenous diltiazem were evaluated in 10 patients with recurrent supraventricular tachycardias. The tachycardia incorporated an accessory pathway in 7 patients and was due to AV nodal reentry in 3 patients. Diltiazem 0.25 mg/kg was administered intravenously over 5 minutes during sustained supraventricular tachycardia. Programmed electrical stimulation was used to restore sinus rhythm if diltiazem failed to terminate the arrhythmia within 10 minutes. Conduction intervals, refractory periods and tachycardia characteristics were evaluated before and immediately after drug administration. Diltiazem did not significantly modify sinus cycle length, AH and HV intervals. Atrial and ventricular effective refractory periods were similar before and after diltiazem. The effective refractory period of the AV node was prolonged by 42 msec after diltiazem (p less than 0.05). Diltiazem increased the tachycardia cycle length from 320 +/- 41 to 353 +/- 36 msec (p less than 0.01) but terminated the arrhythmia in only 2 patients. After diltiazem, supraventricular tachycardia could not be reinitiated in only 2 patients and the tachycardia initiating window was not significantly reduced (56 +/- 26 to 41 +/- 33 msec). The infusion of diltiazem was accomplished without side effects. Thus, 0.25 mg/kg of intravenous diltiazem produces a modest depression of AV nodal function and is not very effective in terminating supraventricular tachycardia or preventing its initiation in this study population. Further studies using higher doses of intravenous diltiazem would be useful to determine its maximal therapeutic benefit in patients with recurrent supraventricular tachycardias.
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PMID:Electrophysiologic effects of intravenous diltiazem in patients with recurrent supraventricular tachycardias. 384 93

Calcium-channel blockers are known to have depressant effects on atrioventricular (AV) nodal conduction and myocardial contractility. Because of these known depressant effects, bepridil hydrochloride, a new, long-acting, antianginal and antiarrhythmic calcium-channel blocker, was administered intravenously to patients without heart failure to determine acute hemodynamic effects. The patients studied had normal ventricular function, were without electrocardiographic conduction disturbances and were taking no drug except sublingual nitroglycerin for at least 24 hours before bepridil infusion. The study protocol included right- and left-sided cardiac catheterization with infusion of bepridil at 2 mg/kg for 15 minutes followed by 1 mg/kg for 15 minutes in 10 patients, and infusion of bepridil at 3 mg/kg for 15 minutes followed by 1 mg/kg for 15 minutes in 8 patients. Pressures, Fick cardiac output, resistances, left ventricular (LV) dP/dt, LV stroke work index and rate-pressure product of the left ventricle were monitored. There were no significant changes during bepridil infusion at either dose for cardiac output, systemic vascular and pulmonary vascular resistances, LV stroke work index, heart rate, arterial blood pressure and rate-pressure product. There was mild depression of LV dP/dt during bepridil infusion. Further, LV end-diastolic pressure, pulmonary capillary wedge pressure and pulmonary arterial pressures were significantly increased during bepridil infusion. There were no apparent changes in AV nodal or intraventricular conduction during bepridil infusion. We conclude that bepridil appears to be a safe drug for intravenous administration despite mild depression of myocardial function in patients with normal baseline hemodynamic function who are not receiving concomitant beta-blocker therapy.
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PMID:Hemodynamic effects of intravenous bepridil in patients with normal left ventricular function. 387 53

The clinical and hemodynamic effects of propranolol, propranolol-verapamil (P-V), propranolol-nifedipine (P-N) and propranolol-diltiazem (P-D) were studied in 19 patients with chronic exertional angina pectoris. A placebo-controlled, double-blind, randomized, crossover study design was used in which patients took each treatment for a 4-week period. The 3 combinations equally reduced the incidence of angina attacks and decreased ST-segment depression. Left ventricular hypokinesia during exercise was lessened and end-systolic volume during exercise decreased with all combinations. Because of a corresponding reduction of normokinetic segmental function, global ejection fraction during exercise remained unchanged. Heart size increased (p less than 0.05) and the PR interval lengthened (p less than 0.001) with P-V and P-D compared to P-N. The largest number of adverse clinical reactions occurred with P-V, whereas the fewest occurred with P-D. Almost all patients preferred combined therapy over propranolol and many favored 1 combination over the others. In summary, when therapy with combined beta- and calcium channel-blocking drugs is planned, P-D should be considered the combination of first choice because of its low incidence of adverse clinical effects. In the presence of possible or definite abnormalities of atrioventricular nodal conduction or decreased left ventricular function, P-N should be considered. Although P-V is associated with frequent adverse reactions, a trial may be warranted if the other combinations are unsuccessful.
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PMID:Clinical and hemodynamic evaluation of propranolol in combination with verapamil, nifedipine and diltiazem in exertional angina pectoris: a placebo-controlled, double-blind, randomized, crossover study. 388 39


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