Electroconvulsive therapy--a current view.
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Antipsychotic Agents↗
Biomedical subjects
B F Hoffman
Publications and source records attributed to B F Hoffman.
Use-dependent block of cardiac sodium channels by quaternary derivatives of lidocaine.
Modulation of the reduction of fast inward sodium current by local anesthetics due to changes in electrical activity has been termed use-dependent block ( Courtney 1975). To determine the mechanisms responsible for use-dependent block of cardiac sodium channels and to compare use-dependent block in cardiac and nerve preparations, we investigated use-dependent block of cardiac sodium channels by the quaternary lidocaine analogues QX -314 and QX -222 (two agents previously studied in nerve). We used canine cardiac Purkinje fibers, and assessed changes in the fast inward sodium current using changes in the maximum rate of rise of the action potential upstroke (Vmax). Two microelectrode voltage clamp and current clamp techniques were used to control membrane potential prior to stimulated upstrokes . Use-dependent block was not affected by shortening the action potential duration during rapid stimulation. Partial recovery from use-dependent block was observed during rapid stimulation with brief depolarizing prepulses terminating immediately prior to the upstroke. Similar prepulses also prevented the development of use-dependent block following an abrupt increase in the stimulation rate. Hyperpolarizing prepulses during rapid stimulation caused recovery from use-dependent block; recovery was greater and more rapid with increasingly negative prepulses . Hyperpolarization during periods of electrical quiescence also caused greater recovery. These results, interpreted using the modulated receptor hypothesis ( Hille 1977; Hondeghem and Katzung 1977), suggest that use-dependent block of cardiac sodium channels by quaternary local anesthetics is due to drug association with the inactivated sodium channel receptor which occurs only after these drugs gain access to the receptor site through open sodium channels.
Action Potentials↗
Cellular and tissue responses to recurrent ventricular tachycardia and fibrillation.
The effects of rapid rhythms on cellular electrical activity depend on the rate of the rhythm, the cell type, and its condition prior to the arrhythmia. Rapid rates can cause major changes in transmembrane ion concentration gradients and the magnitude of these is a function of the transport capacity of the sodium-potassium pump. Thus digitalis can be expected to exert a prominent effect on rate-induced changes. Some of the rate-induced changes can lead to the generation of arrhythmias, as through calcium overload and the development of delayed afterdepolarizations. Since the actions of antiarrhythmic drugs often show use-dependence, the presence in the heart of local anesthetics or certain slow channel blockers will further modify the effect of rapid and irregular rhythms on cellular electrical activity.
Anti-Arrhythmia Agents↗
Demonstration of the mechanisms for arrhythmias in experimental animals.
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Animals↗
Gas sniffing as a form of substance abuse.
The authors review the existing literature on inhalation of gasoline fumes, highlighting the acute and chronic physical and psychological effects. The clinical picture of gas sniffing includes visual hallucinations, changes in consciousness, euphoria, nystagmus, dizziness, weakness and tremors. There is the possibility of rapid recovery, sudden death or brain damage with chronic abuse. When leaded gasoline is abused then blood and urine lead levels and erythrocytic delta-aminolevulinic acid dehydrase (ALAD) levels may be helpful. Although the treatment of acute and chronic gas sniffing syndromes is often supportive and non-specific, when lead levels are high chelated therapy is indicated including British anti-lewisite, calcium disodium versenate or D-penicillamine. We also report our findings on an isolated native Indian population where intentional gas sniffing has reached epidemic proportions. Ten percent of the total population and 25% of the children between 5 and 15 years of age had been identified as gasoline inhalation abusers. In this population, the most important etiological factors included environmental, family and cultural components. The authors emphasize the need to correct the family and social deficiencies in such communities if the incidence of gas sniffing is to be decreased.
Adolescent↗
Pharmacologic antagonism of propranolol in dogs. III. Effects of dopamine-isoproterenol and glucagon on hemodynamics and myocardial oxygen consumption in ischemic hearts during chronic propranolol administration.
In 31 dogs chronically beta blocked with oral propranolol (12 to 14 mg/kg/day), glucagon (20 micrograms/kg) and combined dopamine (10 micrograms/kg/min) and isoproterenol (0.2 micrograms/kg/min) were given intravenously and tested for hemodynamic efficacy. Dogs were divided into four groups. Basal hemodynamics were obtained In Group I (n = 8) without cardiopulmonary bypass. In Group II (n = 8), hemodynamics were studied after 15 minutes of global ischemia during cardiopulmonary bypass. In Group III (n = 8), hemodynamics were studied after regional ischemia produced by ligation of the proximal left anterior descending coronary artery. In Group IV (n = 7), myocardial oxygen consumption and left ventricular mechanics were studied before and after 1 hour of cardiopulmonary bypass. Our results indicate the following: (1) Dopamine-isoproterenol improves hemodynamics in basal, post-global ischemic, and post-regional ischemic states. Glucagon improves hemodynamics either insignificantly or to a lesser extent than dopamine-isoproterenol. Furthermore, glucagon produces a larger increase in heart rate, which is not desirable. (2) Both dopamine-isoproterenol and glucagon increase myocardial oxygen consumption in comparison with control.
Animals↗
Diet pill psychosis: follow-up after 6 years.
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Diethylpropion↗
Studies on overdrive stimulation of canine cardiac Purkinje fibers: maximal diastolic potential as a determinant of the response.
The effects of overdrive stimulation were studied on preparations of isolated canine cardiac Purkinje fibers using standard microelectrode techniques. Preparations were made from false tendons, the subendocardial right bundle branch and 24 hour infarct zone Purkinje fibers. Three types of automaticity were recognized: high potential automaticity occurred in fibers with maximal diastolic potentials greater than -70 mV, intermediate potential automaticity occurred in fibers with maximal diastolic potentials between -61 and -70 mV and low potential automaticity occurred in fibers with maximal diastolic potentials less than -60 mV. Short periods of overdrive (15 seconds or 30 beats) resulted in marked suppression of high potential automaticity, slight suppression of intermediate potential automaticity and little or no suppression of low potential automaticity. The extent of postoverdrive suppression of intermediate potential automaticity was related to the rate and duration of the overdrive train and the amount of hyperpolarization that occurred in the pacemaker fiber. Finally, in three experiments on Purkinje fibers from 24 hour infarct zones, delayed afterdepolarizations occurred. In two of these preparations, overdrive stimulation resulted in biphasic responses (postoverdrive enhancement followed by postoverdrive suppression). The results of this study suggest that it may be possible to design simple electrophysiologic tests to determine whether an automatic arrhythmia is being caused by normal or partially depolarized ectopic pacemakers.
Action Potentials↗
The influence of molecular form of local anesthetic-type antiarrhythmic agents on reduction of the maximum upstroke velocity of canine cardiac Purkinje fibers.
We studied the local anesthetic effects of the quaternary lidocaine analogues QX-314, QX-572, and QX-222, the tertiary amine lidocaine, its analogues tocainide, 6603, 6211, and the neutral local anesthetic benzocaine to determine if molecular charge of antiarrhythmic agents influences their local anesthetic effects on heart fibers. We used standard microelectrode techniques and canine cardiac Purkinje fibers to compare the effects of stimulation rate, drug concentration, and K+-induced changes in resting membrane potential on the reduction of fast inward sodium current using the maximum rate of rise of the action potential upstroke, Vmax, as an index of changes in peak sodium current. Use-dependent block, defined as a modulation of the reduction in Vmax by local anesthetics due to changes in the stimulation rate, was observed with the permanently charged analogues and was most prominent for agents existing predominantly in the charged form, but was absent for the neutral local anesthetic benzocaine. The development of use-dependent block during rapid stimulation preceded by prolonged periods of quiescence was an exponential process which became more rapid with increasing drug concentration. Recovery from use-dependent block during quiescence was an exponential process that was not influenced by similar drug concentration changes. All local anesthetics caused tonic block, defined as a drug-induced reduction of Vmax from control that attained a constant value at slow stimulation rates (cycle length range 15 seconds to 2 minutes) and was not changed by prolonged (up to 8 minutes) periods of quiescence. These findings suggest that the charged form of lidocaine and its analogues is responsible for use-dependent block of cardiac sodium channels.
Anesthetics, Local↗
Antiarrhythmic effects of ethmozin in cardiac Purkinje fibers: suppression of automaticity and abolition of triggering.
The effects of ethmozin were studied on automatic and triggered impulse initiation in isolated canine cardiac Purkinje fibers using standard microelectrode technique. In driven Purkinje fibers with normal (greater than or equal to -80 mV) maximum diastolic potentials, ethmozin (2-4 mg/l or 4.3-8.6 muM) slightly increased the slope of phase 4 depolarization. However, the rate of normal automatic firing in such fibers was decreased by ethmozin and the threshold (take-off) potential of the pacemaker cells was shifted in the depolarizing direction (toward zero potential). In fibers treated with barium chloride (0.10-0.50 mM), "abnormal automaticity" occurred from maximum diastolic potentials of -38 to -68 MV. Ethmozin (2-4 mg/l) consistently slowed and abolished this abnormal automaticity. This appeared to be associated with a decrease in the rate of diastolic depolarization. When lidocaine, 4 or 10 mg/l (17 or 42 muM), was tested on abnormal automaticity induced by barium, it too was found to decrease the rate of diastolic depolarization and decrease the automatic rate. However, lidocaine never terminated barium-induced abnormal automaticity. Ethmozin also consistently abolished abnormal automaticity in Purkinje fibers taken from the endocardial surface of 24- or 48-h infarct zones. Finally, ethmozin (1-4 mg/l or 2.2-8.6 muM) depressed the amplitude of delayed after depolarizations and terminated triggered activity in Purkinje fibers taken from 24-hr infarct zones. Each of these actions could contribute to the antiarrhythmic effects of ethmozin.
Action Potentials↗
Electrotonic modulation of the T wave.
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Bundle-Branch Block↗
Four-contact glove probe method for rapid recording of cardiac electrograms during surgery.
A technique is presented for recording four simultaneous electrograms from the heart during operation for cardiac arrhythmias. this technique permits intraoperative maps of cardiac electrical activity to be constructed more rapidly than is possible with single-point mapping, thereby decreasing the risks to the patient and yielding more information about cardiac events.
Arrhythmias, Cardiac↗
Effects of ouabain and vagal stimulation on sinus nodal function in conscious dogs.
We studied the effects of intravenous ouabain administration (15 micrograms/kg) and vagal stimulation on instrumented conscious dogs. In these dogs, a special electrode was implanted on the epicardial surface over the sinus node and plaque electrodes were placed on the superior vena cava and left atrial appendage. Unipolar sinus electrograms were recorded through the terminals of the sinus electrode paired with the superior vena caval electrode. An electrode also was implanted around the desheathed cervical vagosympathetic trunk, and a coiled polyethylene tube with side holes was implanted cranial to it. Ouabain administration resulted in: (1) an increase in the sinus cycle lengths and sinoatrial intervals and increase in beat-to-beat variation of the sinus cycles and sinoatrial intervals, and (2) periods of sinus pacemaker shift, sinus arrest and sinoatrial block that occurred spontaneously or after atrial overdrive stimulation delivered through the electrode on the left atrial appendage. These effects of ouabain were abolished by intravenous administration of atropine (2 mg). Prior to vagal stimulation, intravenous propranolol (0.5 mg/kg) was administered to block sympathetic responses and 0.75% bupivacaine was injected through the polyethylene tube to block afferent transmission. Vagal stimulation in conscious dogs resulted in two types of responses: (1) slowing of sinus pacemaker rate accompanied by a decrease in diastolic slope and followed by sinus pacemaker shifts, and (2) gradual prolongation of the sinoatrial intervals followed by failure of sinoatrial conduction. An intravenous bolus of acetylcholine (0.1 mg) resulted in a response of type 2 in dogs in which vagal stimulation produced a response of type 1. The marked similarity between the effects of ouabain and vagal stimulation on sinus function and the abolition of the effects of ouabain by atropine suggest that the ouabain effects are vagally mediated.
Action Potentials↗
Maprotiline and seizures.
Maprotiline has been reported to be less likely to cause epileptic seizures than the tricyclic antidepressants. The authors describe two cases in which patients suffered their first epileptic attacks while on therapeutic doses of maprotiline. They recommend that the newer antidepressants, as well as the tricyclics, should not be used with the aliphatic neuroleptics because of a possible additive or synergistic epileptic effect. If patients are to be withdrawn from C.N.S. depressants, then this should be accomplished prior to initiation of antidepressant therapy. Patients who are predisposed to seizures should have lower initial doses of antidepressants.
Adult↗
Reversible neurosyphilis presenting as chronic mania.
A patient is described who was diagnosed in an outpatient department as having paranoid psychosis and later chronic schizophrenia, which was treated with chlorpromazine. Two years later, the patient was admitted to hospital because of increasing confusion, disorganization, and numerous manic symptoms. Physical examination and serologic examination of blood and CSF confirmed the diagnosis of general paresis. Correct treatment led to the eventual discontinuation of neuroleptics and the cessation of paranoid and manic symptoms.
Affective Disorders, Psychotic↗
To tell or not to tell.
The three articles in this At Issue section all deal with important aspects of patient education. In the article below, B.F. Hoffmann discusses the problem of telling the patient this diagnosis, and the therapeutic issues that must be considered in this process. In the second article, M. Linden and R. Chaskel focus on issues of informed consent in patients undergoing long-term pharmacotherapy, and present results of a study that assesses how much patients really know about the benefits and risks of their treatment program. Finally, C. Pilsecker describes his experiences in teaching a class about schizophrenia to hospitalized patients, and their understandable difficulties in accepting the fact that even the best, most recent research studies provide few certain answers about this puzzling disorder.
Humans↗
Cellular mechanisms for cardiac arrhythmias.
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Animals↗
The effects on atrial electrophysiology and structure of surgically induced right atrial enlargement in dogs.
We evaluated the relationship between susceptibility to arrhythmias caused by right atrial (RA) enlargement and alterations in transmembrane potentials and ultrastructure. RA enlargement was produced in eight dogs (TI) by excising the septal cusp of the tricuspid valve through a right atriotomy and constricting the pulmonary artery. This procedure resulted in RA dilation and hypertrophy. Four sham-operated dogs (S) also were studied. Neither TI nor S dogs developed spontaneous atrial arrhythmias. Atrial overdrive (OD) and premature stimulation (PS) were used to initiate and terminate arrhythmias. At 2 weeks and for 20 to 30 weeks after surgical preparation, TI dogs were more susceptible to arrhythmias than S dogs. The duration of arrhythmias exceeded 10 minutes more often in TI dogs than in S dogs. Sixty-one percent of all arrhythmias in the TI dogs had rates of 320-450 impulses/min, and electrogram and ECG characteristics of atrial flutter (type II rhythm), whereas no S dogs developed rhythms with these slower rates. The type II rhythms were persistent, 30% lasting longer than 30 minutes, while 22% lasted more than 60 minutes. Transmembrane potentials recorded in vitro from the RA free wall of TI dogs, and responses to norepinephrine and acetylcholine were not different from control. Histological and ultrastructural studies on TI atria showed hypertrophy of fibers and some increase in connective tissue between cells. These results suggests that altered susceptibility to long-lasting arrhythmias need not be associated with significant abnormalities of cellular electrophysiology.
Animals↗