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)

Reentrant ventricular arrhythmias (RVA) were analyzed in dogs 3--7 days after ligation of the anterior descending coronary artery using averaged "composite" recordings of electrical activity of reentrant pathways (RP) from the epicardial surface of the infarction zone (IZ). Verapamil (V) and D-600 (D) (0.2--0.5 mg/kg i.v.) resulted in slight-to-moderate improvement of conduction in RP with abolition of spontaneous RVA and RVA initiated by premature depolarizations. The effect of V was not blocked by pretreatment with propranolol (0.5 mg/kg i.v.). Using a standard microelectrode technique and strips of epicardial muscle from the IZ, D (0.5--1 X 10(-6) g/ml) slightly improved the upstroke velocity and membrane responses of depressed ischemic cells. In contrast, tetrodotoxin (5 X 10(-7) g/ml) further depressed or abolished action potentials of ischemic cells. We conclude: 1) the moderate antiarrhythmic effect of V and D on RVA is the result of improved conduction in RP; 2) this action is partly explained by improvement of a depressed sodium channel and is not related to catecholamine release; 3) slow-response action potentials play no significant role in the genesis of ischemia-related RVA, which probably results from depression of the fast response.
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PMID:Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel". 45 24

The effect of verapamil on Ca2+ and Mg2+ accumulation was investigated in isolated rat kidney cortex mitochondria. For the 50% inhibition of Ca2+ accumulation, 2 x 10(-4) M verapamil concentration was required in the presence of ATP (2 mM) and phosphate (5 mM). Omission of phosphate from the medium increased the inhibitory effect of verapamil on Ca2+ accumulation. Verapamil had no effect on Ca2+ accumulation in the presence of both ATP and succinate (7.8 mM), but further addition of phosphate resulted in a significant inhibition of Ca2+ accumulation by verapamil. Mg2+ accumulation of mitochondria was similarly depressed by verapamil. The same tendency was found as for the modification of verapamil effect by acetate in mitochondrial Ca2+ and Mg2+ accumulation. Succinate oxidation of mitochondria was not affected by verapamil in the absence of phosphate, but was inhibited by verapamil in the presence of phosphate. Therefore, it seemed reasonable to assume that the depression of Ca2+ and Mg2+ transport of mitochondria by verapamil is modulated by permeant anions.
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PMID:Effect of verapamil on the calcium and magnesium transports of rat kidney cortex mitochondria. 53 83

Previous studies have demonstrated that verapamil possess potent anti-arrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Isolated tissue studies performed in rabbit right atrium demonstrated that prompt and prominent slowing of the sinus rate even at a dose of 1 X 10(-7) mol . litre-1. This dose produced significant decrease in action potential amplitude and phase 4 slope, shifted the 'threshold potential' to a less negative value, prolonged action potential duration but did not change maximum diastolic potential. At this dose of verapamil, sinoatrial conduction time prolonged significantly (control: 40.0 +/- 4.8 ms; 1 X 10(-7) mol . litre-1 verapamil: 50.0 +/- 6.4 ms). Purkinje fibre studies demonstrated decreases in dV/dt, resting potential, total amplitude, action potential duration at 75, 95% of recovery and effective refractory period only after exposure to greater than or equal to 1 X 10(-5) mol . litre-1 verapamil. Electrophysiological studies in conscious dogs demonstrated, after bolus administration of verapamil, progressive increases in the A-H interval and heart rate, but no changes in H-V and QRS intervals. Anaesthetised dog studies showed the lack of significant effect on A-H and H-V intervals or QRS duration regardless of the bolus dose of verapamil. However, verapamil produced statistically significant increases in heart rate after 0.025 mg . kg-1. Verapamil administration did not produce a statistically significant change in escape pacemaker rate in vagal stimulation experiments or with spontaneously beating isolated Purkinje fibres. Finally, the effect of increasing intravenous bolus does of verapamil on ischaemic arrhythmias was studied in five conscious dogs 24 h following LAD ligation. Only one dog with ventricular tachycardia and another dog with junctional escape rhythm were converted to sinus rhythm after the 0.05 mg . kg-1 and 0.2 mg . kg-1 doses, respectively. In conclusion, these studies demonstrated that administration of verapamil specifically depresses tissue with electrophysiological dependence on slow channel current. Therefore, sinus and A-V nodal events would be suppressed and slow-channel mediated events in ischaemic ventricle also would be inhibited. Clinically, acute administration of verapamil would lead to depression of sinus and A-V nodal function as well as potentially eliminate slow current mechanisms in ischaemic arrhythmias.
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PMID:Electrophysiological effects of verapamil. 74 94

The effect of various local anesthetics and other substances known to modify calcium fluxes in cells, on submaximal responses of guinea-pig ileum to substance P, acetylcholine, histamine and barium chloride was determined. Procaine caused a dose-related depression of the response to all the agonists but the response to substance P was far less susceptible to this depression. Lidocaine, bupivacaine, pramoxine and W 6211 also caused a lower degree of attenuation of the response to substance P than the responses to acetylcholine, histamine and barium chloride. Verapamil caused a dose-related depression of responses to all the agonists equally. The use of calcium-free solutions abolished responses to substance P, acetylcholine and histamine. The response to barium chloride was less affected by calcium withdrawal but was reduced markedly. In the presence of 10 mM lanthanum chloride, the response to all the agonists was abolished. The relative resistance of the substance P responses to antagonism by local anesthetics suggests that different and more efficient channels for calcium entry into the smooth muscle cell are involved.
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PMID:Interactions between local anesthetics and spasmogens on the guinea-pig ileum. 93 95

Verapamil (Isoptin) caused a dose-dependent peripheral vasodilation, increase in myocardial contractility, and tachycardia in the anaesthetized dog. Propranolol pretreatment blocked the cardiac stimulation following verapamil but the vasodilation was unaltered. Inflation of a thoracic aortic balloon prevented the fall in intravascular pressure and reduced the tachycardia and positive inotropic responses. These experiments suggest that clinical doses of verapamil cause peripheral vasodilation which leads to a sympathetic reflex induced increase in heart rate and myocardial contractility. Verapamil also had a direct myocardial depressant action which became evident at doses above the range used clinically. The drug increased the PR interval in conscious dogs for up to 60 minutes. This effect was partly mediated through cholinergic stimulation and partly through a direct depression on atrioventricular conduction.
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PMID:Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility and atrioventricular conduction. 99 Nov 62

The effect of verapamil were studied on 50 episodes of supraventricular and ventricular tachycardia in 44 patients. An i.v. dose of 0.10 to 0.15 mg/kg. was used. In 5 cases His bundle electrograms were obtained while maximal dp/dt was determined in 7 others. Sinus rhythm was obtained in 21 (81%) of 26 cases of PSVT. In all cases of rapid atrial fibrillation (n-11), an important decrease in the ventricular response was elicited. Of 7 cases of atrial flutter, verapamil induced sinus rhythm in 3 and a significant decrease in the ventricular rate in 3 others. In 2 out of 6 cases ventricular tachycardia reverted to sinus rhythm. The latency time between the injection and the manifestation of the effect ranged from 2 to 4 minutes. A slight and short-lasting depression of dp/dt was observed in all cases studied. Verapamil produced an increase in the A-H interval in 4 of the 5 cases studied with His bundle recordings. Verapamil was found to be a useful drug to suppress PSVT, to decrease the ventricular response in flutter or atrial fibrillation and to convert some ventricular tachycardias to sinus rhythm. Verapamil should be used with caution in previously digitalized patients and is contraindicated when there is S-A node dysfunction as in the tachycardia-bradycardia syndrome.
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PMID:[Antiarrhythmic effects of verapamil]. 108 54

A pattern analysis of inotropic actions was carried out on isotonically chortening cat papillary muscles exposed to (+/-)-verapamil and (+/-)-D 600 and compared to other Ca-antagonistic interventions. 1. (+/-)-Verapamil (1--5mug/ml) leaves contraction amplitudes nearly unchanged at 6/min, whereas at 60/min more than 90% depression (5 mug/ml) occurs. (+/-)-D 600 is about twice as effective as (+/-)-berapamil. 2. An increase of [Ca2+]O in the presence of (+/-)-verapamil or (+/-)-D 600 does not restitute the normal amplitude-frequency relationship. There is only a shift toward higher contraction amplitudes. 3. (+/-)-Verapamil and (+/-)-D 600 lead to typical biphasic inotropic transients after step changes of the friving rhythm. First a fast and (at higher frequencies) very pronounced negative staircase occurs, followed by a rather slowly developing positive staircase. 4. These drug effects contrast to the effects of lowering [Ca2+]O or of adding Ni2+ or La3+, which all produce a rather uniform depression of contraction amplitudes at all frequencies and do not elicit staircase phenomena such as seen under the influence of (+/-)-verapamil or (+/-)-D 600. 5. In contrast to the action of Ni2+, La3+ or low [Ca2+]O, (+/-)-verapamil slows down the restitution kinetics of Ca-reavailability from internal stores as determined by the amplitude of test contractions elicited after various periods of rest. 6. Drug-induced changes in the time course of the transmembrane action potential as depending on frequency may partially but not fully explain the contractile phenomena. 7. Possible interpretations as to the sites where (+/-)-verapamil or (+/-)-D 600 interferes with cardiac excitation-contraction coupling are given by the aid of a multicompartment model. This model describes excitation-contraction coupling in terms of transmembrane and intracellular Ca-movements.
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PMID:Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. I. Pattern of inotropic effects of the racemic compounds. 117 69

The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials.
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PMID:The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig. 125 85

Paroxysmal supraventricular tachycardia is the most common sustained cardiac arrhythmia in pregnant women. Because nearly 50% of these supraventricular tachyarrhythmias fail to respond to vagal maneuvers, other therapies are used, including electrocardioversion and pharmacologic agents. Propranolol, verapamil, and adenosine have Food and Drug Administration-approved labeling for acute termination of supraventricular tachycardia. Verapamil has been the most commonly used agent in the general population but it has several shortcomings, such as its potential to cause or exacerbate systemic hypotension, congestive heart failure, bradyarrhythmias, and ventricular fibrillation. In addition, verapamil readily crosses the placenta and has been shown to cause fetal bradycardia, heart block, depression of contractility, and hypotension. Adenosine has several advantages over verapamil, including rapid onset, brevity of side effects, theoretical safety, and probable lack of placental transfer. Adenosine ultimately may prove to be the preferred agent for termination of paroxysmal supraventricular tachycardia in the gravid woman.
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PMID:Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia. 149 12

The purpose of this study was to evaluate the cardiac electrophysiological effects of McN-5691, a new calcium-channel blocking antihypertensive drug. In anesthetized dogs, the primary electrophysiological effect of McN-5691 was dose-related prolongation of AV-nodal conduction time and refractoriness (0.1-1.0 mg/kg i.v.), which correlated with McN-5691 plasma levels. There were no significant effects on atrial or ventricular conduction times, QTc, or ventricular monophasic action potential duration. This profile was similar to that of verapamil. McN-5691 caused concentration-related, rate-dependent reductions in Vmax and amplitude of slow-response action potentials in guinea pig papillary muscle: ED-20% for depression of Vmax was 0.72 +/- 0.32 microM. Verapamil was more potent in depressing these action potentials: ED-20% for depression of Vmax was 0.03 +/- 0.01 microM. McN-5691 also caused rate-dependent reduction in Vmax and amplitude of canine Purkinje fiber action potentials, but only at relatively high concentrations: ED-20% for depression of Vmax was 55 +/- 12 microM. McN-5691 also reduced the action potential duration (0.3-30 microM) without affecting the slope of phase 4 depolarization and the maximum diastolic potential. Verapamil also reduced Vmax in Purkinje fibers (ED-20% for depression of Vmax was 32 +/- 3 microM) and shortened the action potential duration. The results show that McN-5691 has cardiac electrophysiological effects consistent with blockade of the slow inward calcium current, and that this activity occurs at concentrations well below those having local anesthetic activity. In addition, its lower potency in comparison to verapamil in depressing slow responses suggests a lesser propensity for negative inotropic effects.
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PMID:Cardiac electrophysiologic effects of McN-5691, a new calcium-channel blocking antihypertensive agent. 170 95


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