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)

Diltiazem is an orally and intravenously active calcium channel blocking agent shown to be an effective and well-tolerated treatment for stable angina and angina due to coronary artery spasm. Its efficacy in these diseases has generally been similar to that of nifedipine or verapamil - alternative calcium channel blockers with which diltiazem has many electrophysiological, haemodynamic, and antiarrhythmic similarities. The antianginal mechanism of diltiazem cannot be precisely described; however, it appears to increase myocardial oxygen supply and decrease myocardial oxygen demand, mainly by coronary artery dilatation and/or via both direct and indirect haemodynamic alterations. Diltiazem has also shown substantial efficacy in the treatment of unstable angina, hypertension, and supraventricular tachyarrhythmias, but further study is necessary before its place in the treatment of these diseases may be clearly established. Although headache due to peripheral vasodilatation and depression of atrioventricular nodal conduction may be troublesome, side effects occur in only 2 to 10% of patients receiving diltiazem and are generally minor in nature. Thus, diltiazem offers a worthwhile alternative to other agents currently available for the treatment of angina pectoris. Although the infrequency of serious side effects may offer an advantage, its relative place in therapy compared with that of other calcium channel blockers remains to be clarified.
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PMID:Diltiazem. A review of its pharmacological properties and therapeutic efficacy. 389 2

The effects of three purine derivatives of adenine, adenosine triphosphate (Striadyne), purified adenosine triphosphate and adenosine, on conduction tissue, were studied in closed chest dogs with endocavitary recording catheters. The dogs were anaesthetised with pentobarbital and ventilated, then three bipolar catheters were positioned to allow atrial pacing and recordings of atrial and His bundle potentials. The purines studied were administered by rapid bolus intravenous injection. The dosage was identical based on a predetermined dose-response curve (dose of 2 mg/kg). The study of the effects on atrioventricular conduction was carried out before and after administration of antagonists: atropine, 0.08 mg/kg and aminophylline, 10 mg/kg. Twelve dogs were studied for each purine: 6 with initial premedication with atropine and then aminophylline, and 6 with the inverse sequence. Lengthening of AV conduction was due exclusively to nodal depression. No variation in the HV interval was observed (HV = 35 +/- 4 ms). Lengthening of AH interval was observed very soon after injection of the drugs (5 to 10 seconds) with a peak effect between 20 and 40 seconds. Reversion to the initial value always occurred in under 2 minutes. In the model studied, Striadyne and purified adenosine triphosphate were much more powerful than adenosine, both in intensity and duration; high degree AV block was obtained in 10 out of 12 cases with Striadyne and in 8 out of 12 cases with purified adenosine triphosphate, but in only 2 out of 12 cases with adenosine. The use of specific antagonists demonstrated the different modes of action of the three purines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mode of action of purinergic derivatives of adenine on auriculo-ventricular conduction. Experimental study in dogs]. 391 75

In 15 adult dogs ventricular echoes were elicited during sinus rhythm by incremental ventricular pacing and during atrioventricular (AV) junctional rhythm by depressing simultaneously AV junctional automaticity and retrograde AV nodal conduction. Concomitant slowing of AV junctional automaticity and conduction was achieved by selective intranodal administration of verapamil. In three dogs incremental pacing from either ventricle failed to retrogradely activate the atria, and in each case the site of block was found to be in the AV node. In two dogs with retrograde atrial capture there was little or no rate-dependency of retrograde ventriculoatrial (VA) conduction. During incremental ventricular pacing a single ventricular echo beat was observed in 10 of the 12 dogs that had atrial capture, and the atrium appears to be an essential link in the production of each ventricular echo. Ventricular echo occurred when the time allotted for retrograde VA conduction amounted to 70 +/- 4% of the duration of the ventricular pacing cycle length. During AV junctional rhythm, a single ventricular echo was elicited in half of the dogs and in each of those cases intranodal verapamil produced a profound depression of retrograde VA conduction. These experiments suggest that retrograde AV nodal longitudinal dissociation occurs in the slow current-dependent cells of the AV node.
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PMID:Ventricular echo beats during ventricular pacing or junctional bradycardia: studies in the normal canine heart. 395 88

Associated electrophysiologic abnormalities and site of delay were studied in 20 patients, aged 1.5 to 16.5 years, with congenital heart disease and first-degree atrioventricular (AV) block (PR interval above the 98th percentile for age and heart rate). Eight of the 20 patients with first-degree AV block were studied after 1 or more cardiovascular operations. Refractory periods of the atrium, AV node, His-Purkinje system and ventricle were determined. As a further test for AV nodal integrity, rapid atrial pacing was performed and the cycle at which Wenckebach periodicity occurred was noted. Four groups were identified. Group I included 4 patients (20%) with intraatrial conduction delay (long PA interval). Three patients had depressed sinus nodal function and 1 had depressed AV nodal function. Group II included 7 patients (35%) with AV nodal delay (long AH interval). One patient had sinus nodal depression and 2 had AV nodal depression (prolonged AV nodal refractory period or Wenckebach at a long paced cycle length). Group III included 3 patients (15%) with His-Purkinje delay (long HV interval). Measured functions were normal in all patients. Group IV included 6 patients (30%) with normal or high normal intracardiac intervals with long PR. One patient had sinus nodal dysfunction, 2 patients had long atrial refractory periods, 1 had AV nodal depression; 2 had long refractory period of the His-Purkinje system, and 1 had long ventricular refractory period. Atrial flutter was induced in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Site of conduction delay and electrophysiologic significance of first-degree atrioventricular block in children with heart disease. 399 64

1 Low doses of tiprenolol (0.01-0.02 mg/kg) and propranolol (0.05 mg/kg) abolished the ventricular arrhythmias produced by the intravenous injection of adrenaline in anaesthetized dogs respired with halothane.2 Larger doses of tiprenolol (2.0-4.0 mg/kg) restored sinus rhythm in four of five dogs with ventricular tachycardia produced by toxic doses of ouabain. Propranolol (2.0-4.0 mg/kg) had the same effect in each of four dogs.3 Both tiprenolol (4.0-8.0 mg/kg) and propranolol (4.0 mg/kg) increased the frequency of sinus beats and reduced the ventricular rate in dogs with ventricular tachycardia 20-44 h after ligation of a coronary artery.4 Practolol (0.5-16.0 mg/kg) did not reduce the ventricular rate or increase the frequency of sinus beats in dogs with ventricular tachycardia after ligation of a coronary artery.5 In dogs with ouabain-induced ventricular tachycardia mean arterial pressure was reduced after the administration of tiprenolol (0.5-8.0 mg/kg) or propranolol (4.0-8.0 mg/kg). Depression of sinus and atrioventricular nodal function, and of intraventricular conduction developed in some of the dogs given tiprenolol (4-8 mg/kg) or propranolol (8.0 mg/kg).6 The administration of tiprenolol (1.0-8.0 mg/kg) or propranolol (4.0-8.0 mg/kg) depressed the arterial pressure and caused the deaths of some dogs in which a coronary artery had been ligated. Such deaths did not occur in the group which had been given toxic doses of ouabain.
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PMID:Effects of tiprenolol, practolol and propranolol on experimental ventricular tachyarrhythmias. 415 71

With the purpose of studying the interactions between sino-atrial (S-A) node and His bundle escape rhythms (HBER), negative chronotropic agents (verapamil, manganese and droperidol) were directly injected in the canine S-A node through its cannulated and autoperfused artery. HBER followed S-A node depression assessed by His bundle electrograms. A well established correlation was found between HBER and S-A node initial rate. His bundle recovery time following an atrial overdrive was 50 times larger than the S-A node recovery time. HBER was found to be more sensitive to sympathetic blockade than to vagal influences. It is concluded that 1) recovery time following overdrive stimulation is a valid index reflecting sinus nodal function; 2) HBER commonly results from selective depression of the S-A node not only depends on rate but also on overdrive suppression; 4) HBER is more sensitive to sympatheticmodulation.
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PMID:Experimental His bundle escape rhythms. 449 16

1. A new method is described for recording external longitudinal currents from single undissected nerve fibres in rat ventral roots. The method permits identification of the sites of fifteen or more successive nodes of Ranvier in a given single fibre and the measurement of internodal conduction times between them.2. Average internodal conduction time for normal ventral root fibres of internodal length between 0.75 and 1.45 mm is 19.7 +/- 4.6 (S.D.) musec at 37 degrees C. Internodal conduction time appeared to show a minimum for fibres of internodal length 1.0 mm.3. Ventral roots were demyelinated by focal application of diphtheria toxin. Although conduction is markedly slowed in demyelinated fibres, sites of inward membrane current remain spatially separated indicating that conduction remains saltatory to the point of conduction block rather than becoming continuous as in unmyelinated fibres.4. Slowing of conduction appears to be due to changes in the passive electrical properties of the internodal myelin. Evidence is presented suggesting that there is an increase in internodal capacitance and a decrease in internodal transverse resistance at internodes of demyelinated fibres; such changes would have the effect of delaying excitation at the nodes. The changes in passive electrical properties, which appear to be primarily in the vicinity of the nodes, would be consistent with the pathological changes observed in demyelinated fibres.5. Internodal conduction times in demyelinated fibres have ranged from normal (26 musec at 30 degrees C) to more than 600 musec. There is a great variation in internodal conduction time at successive internodes of a given single fibre; this presumably reflects the varying severity of demyelination of successive internodes.6. As in normal fibres, nodes of demyelinated fibres generate less current when excited by the second of two closely spaced impulses. This results in an increased internodal conduction time for the second impulse and, at a critically short interstimulus interval, conduction block of the second impulse.7. The increased refractory period of transmission of internodes with increased internodal conduction times is a consequence of the decreased ability of such internodes to sustain propagation in the face of small decreases in nodal current.8. During tetanic stimulation, increases in internodal conduction time are associated with corresponding decreases in nodal current generated by the node proximal to the internode in question.9. It is suggested that changes in the magnitude of the nodal current during repetitive activity are due to changes in transmembrane concentration gradients of sodium, the increased internodal conduction time and eventual conduction block during tetanic stimulation being caused by intracellular sodium accumulation.10. Intracellular sodium accumulation is also offered as the explanation for the post-tetanic depression seen in demyelinated fibres.
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PMID:Internodal conduction in undissected demyelinated nerve fibres. 464 44

The administration of beta-receptor blocking drugs and antiarrhythmic drugs in close proximity may result in hemodynamic, electrophysiologic, or pharmacokinetic interactions. We examined the hemodynamic and electrophysiologic effects of 0.20 mg/kg intravenous metoprolol followed by a 15-minute infusion of 0.75 mg/kg/min tocainide. In the six patients sutided, metoprolol produced a fall in cardiac rate and output which was not further altered by tocainide. Both drugs decreased peak left ventricular (LV) dP/dt, ejection fraction, and mean Vcf. There was no change in LV end-diastolic pressure or echo dimension and in clinical ill effects. In eight patients without sinus A-V nodal disease electrophysiologic studies showed mild depression of A-V conduction by metoprolol. Tocainide depressed sinus node function and shortened the functional refractory period of the His-Purkinje system. There were no clinical sequelae. However, three patients with preexisting electrophysiologic abnormalities developed asystole. There was no evidence of pharmacokinetic interaction. It is concluded that metoprolol and tocainide can be given concurrently with reasonable safety to cardiac patients without electrophysiologic abnormalities.
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PMID:Hemodynamic and electrophysiologic interactions between antiarrhythmic drugs and beta blockers, with special reference to tocainide. 610 7

1 Atrio-ventricular conduction and its modifications induced by six beta-adrenoceptor blocking agents and isoprenaline have been investigated in the anaesthetized dog using the extrastimulus technique and measuring atrial (AERP), nodal (NERP), global (GERP) effective refractory periods as well as global functional refractory period (GFRP). 2 When beta-adrenoceptor blockade was produced by (+/-)-propranolol (beta 1 + beta 2-adrenoceptor blockade) which is devoid of intrinsic sympathomimetic activity (ISA) but has membrane stabilizing effects (MSE), sotalol (beta 1 + beta 2-adrenoceptor blockade, no ISA, no MSE) and atenolol (beta 1-adrenoceptor blockade, no ISA, no MSE), all parameters were significantly increased. When beta-adrenoceptor blockade was achieved with pindolol (beta 1 + beta 2-adrenoceptor blockade) and practolol (beta 1-adrenoceptor blockade) which have ISA but no MSE, all parameters remained unchanged, as was also the case with (+)-propranolol, which has MSE but neither ISA nor beta-adrenolytic properties. 3 Isoprenaline at high doses significantly reduced the refractory periods but when infusion was stopped, marked but reversible conduction depression was observed. 4 It thus appears that beta-adrenoceptor blockade but not MSE is responsible for the onset of atrial and AV-conduction impairment and that ISA affords protection against this impairment.
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PMID:Beta-adrenoceptor blockade and atrio-ventricular conduction in dogs. Role of intrinsic sympathomimetic activity. 612 66

The effects of a newly synthetic alpha- and beta-adrenoceptor blocking agent, YM-09538, on SA nodal pacemaker activity and contractility of atria and intact dogs were studied using isolated and blood-perfused canine atrial muscle preparations supported by a donor dog. Intravenous administration of YM-09538 (10-100 micrograms/Kg) caused hypotension without tachycardia, but was accompanied with bradycardia in anesthetized dogs. In these cases, the SA nodal pacemaker activity and atrial contractility in isolated atria was influenced little. This indicates that the concentration of YM-00538 that induces hypotension has no direct cardiac effects. Direct administration of YM-09538 to isolated atria caused dose-dependent negative chronotropic and inotropic effects, and the potency was 3-30 times less than that of propranolol. In electrically paced preparations, a large dose of YM-09538 produced a uniform depression of the developed tension at all frequencies examined (2-3 Hz). On the other hand, verapamil caused a greater suppression of developed tension at higher frequencies, indicating that the mode of action of YM-09538 is different from that of verapamil.
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PMID:Cardiac effects of YM-09538, a new alpha- and beta-adrenoceptor blocking agent, on SA nodal pacemaker activity and contractility in isolated atria and intact dogs. 612 20


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