Beta-adrenergic blocking agents: review and update.
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Adrenergic beta-Antagonists↗
Biomedical subjects
J Kupersmith
Publications and source records attributed to J Kupersmith.
Myopotential interference with DDD pacemakers: endocardial electrographic telemetry in the diagnosis of pacemaker-related arrhythmias.
Skeletal myopotentials may inhibit the output of unipolar demand ventricular pacemakers, resulting in protracted episodes of asystole in susceptible patients. The new DDD-mode pacemakers have, in addition to a unipolar ventricular lead, a unipolar atrial lead to enable atrioventricular sequential or atrial synchronous function. During clinical investigation of a new dual-unipolar cardiac pacing system programmed to operate in the DDD mode (Pacesetter AFP models 281 and 283), 6 patients were noted (5 men and 1 woman, aged 22 to 68 years) who manifested paroxysmal acceleration of ventricular pacing rate approaching the maximal tracking rate. Two patients also had abrupt slowing or cessation of ventricular output. With the use of atrial electrographic recordings (obtained with telemetry), the following mechanisms of rate change were found: myopotential tracking, myopotential inhibition, interference-mode asynchronous operation, sudden increases in sinus rate, and pacemaker-mediated reentrant tachycardia. In all patients, reprogramming of the implanted devices, based on telemetered atrial electrography, resulted in disappearance of the arrhythmias and loss of symptoms while maintaining the DDD pacing mode. Thus, several mechanisms of rhythm disturbances are peculiar to dual-chamber cardiac pacing systems that use unipolar electrodes. Endocardial telemetry combined with extensive programming capability offers the best opportunity for proper diagnosis and management of these problems.
Adult↗
Long-term antiarrhythmic therapy. Problem of low drug levels and patient noncompliance.
Maintenance of adequate serum blood levels is crucial to successful antiarrhythmic therapy. Serum levels of four antiarrhythmic agents (long-acting procainamide, quinidine sulfate, quinidine gluconate, and disopyramide) were determined in 98 consecutive ambulatory patients receiving long-term oral therapy. Medication dosages, dosing intervals, and time elapsed from last dosage until blood sampling were determined. Seventy-five patients (76.5 percent) had subtherapeutic blood levels (with mean levels less than 50 percent of the suggested minimum), and only 22 patients (22.5 percent) had therapeutic levels. Even among the 61 patients who claimed to have taken their medications within the six hours prior to blood sampling, 43 (70 percent) had subtherapeutic levels. These ratios held among all subgroups studied. Physicians should be aware of the high proportion of patients receiving long-term oral antiarrhythmic therapy with inadequate serum blood levels when planning therapeutic regimens.
Adult↗
Acute effects of oral labetalol on myocardial conduction after coronary artery bypass grafting.
Cardiac electrophysiologic effects of a single oral dose of labetalol were determined in seven patients 4 to 9 days after a coronary artery bypass graft. Surface ECG and bipolar electrograms recorded from temporary pacing wires affixed to the normal right ventricle and abnormal left ventricle at the time of surgery were used to determine conduction intervals. Electrophysiologic parameters were recorded during fixed-rate atrial pacing. Sinus heart rate and blood pressure were monitored. Three patients received 100 mg and four patients received 200 mg labetalol. The drug had no significant effect on intraventricular conduction intervals or QRS duration. It did not significantly influence sinus heart rate or AV conduction time, but in two patients there was prolongation in AV conduction that may have been drug-induced. Labetalol induced a modest but significant decrease in systolic and diastolic blood pressure. In another study propranolol, unlike labetalol, had prolonged AV and intraventricular conduction in the abnormal left ventricle, but not in the normal right ventricle. The absence of these effects with labetalol may reflect lesser local anesthetic effect on intraventricular conduction and an alpha-adrenergic blocking effect that interferes with beta-blockade-induced prolongation of AV conduction.
Administration, Oral↗
Monitoring of antiarrhythmic drug levels: values and pitfalls.
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Acecainide↗
P & T Committee roundtable discussion: Eastern region. Part I.
A series of regional roundtable discussions regarding the successful operation of Pharmacy and Therapeutics (P & T) Committees has been conducted by Hospital Formulary. Representatives from private hospitals, university and teaching hospitals, as well as Veterans Administration medical centers discuss committee profile, constituency, function, mechanics, and criteria for establishing a successful formulary within an institution. The sessions were taped, and the edited transcription is provided in the following article.
Hospitals↗
P & T Committee roundtable discussion: Eastern region Pt. II.
A series of regional roundtable discussions regarding the successful operation of Pharmacy and Therapeutics (P & T) Committees has been conducted by Hospital Formulary. Representatives from private hospitals; university and teaching hospitals, as well as Veterans Administration medical centers have participated to ensure that different aspects of P & T Committee performance are demonstrated. issues regarding committee profile, constituency, function, and mechanics are discussed, as are criteria for establishing a successful formulary within an institution. The sessions were taped, and the edited transcription is provided in the following article.
Cost Control↗
Effects of phencyclidine on cardiac action potential: pH dependence and structure-activity relationships.
The effects of phencyclidine [1-(1-phenylcyclohexyl)-piperidine; PCP] on cardiac action potential duration (APD) were compared to those of some of its derivatives, in strips of isolated frog ventricular muscle perfused with normal Ringer solution. We studied compounds with PCP-like behavioral actions (N-ethyl-1-phenyl-cyclohexylamine: PCE; and m-amino-PCP) as well as behaviorally inactive analogs (m-nitro-PCP; the quaternary derivative PCP-methyl iodide; and various fragments of the PCP molecule). Exposure to PCP, 3 microM to 1 mM, produced reversible, dose- and pH-dependent prolongations, of the APD to over 100% above control. The observed effects of the drugs are compatible with a mechanism of blockade of potassium conductance. An intracellular site for this action is suggested by: (i) the inactivity of the quaternary analog; (ii) the marked increase in the potency of the compounds when the external pH is changed in the region of their respective pKa values to increase the concentration of the unionized species; and (iii) the pronounced acceleration of the termination of the PCP effect by washout with a series of buffer solutions with decreasing pH values. The rank order of potency of the compounds in lengthening APD (PCE greater than m-amino PCP greater than PCP much much greater than m-nitro-PCP) is the same as reported from other pharmacological studies of specific PCP actions, and matches the rank of behavioral activity of the drugs.
Action Potentials↗
Spatial distribution of [14C]-lidocaine and blood flow in transmural and lateral border zones of ischemic canine myocardium.
The purpose of this study was to determine the spatial distribution of lidocaine relative to blood flow in ischemic, normal and border zone canine myocardium. Ischemic zone tissue was distinguished from normal zone tissue by a special microsphere technique in adjacent sections 4 to 5 mm wide from the center to the lateral border of the ischemic region in 14 open chest dogs. Gamma-labeled microspheres were separated by a special technique from carbon-14 ([14C])-lidocaine in the same tissue sample. Blood flow (mean value +/- 1 standard deviation) was reduced to 46 +/- 25 percent of normal in the ischemic subepicardium and 17 +/- 18 percent of normal in the subendocardium. [14C]-lidocaine was 0.56 +/- 0.12 microgram/g in normal myocardium 10 minutes after bolus injection of [14C]-lidocaine; it was reduced to 91 +/- 15 percent of normal in ischemic subepicardium and 58 +/- 12 percent of normal in the subendocardium. Blood flow and lidocaine concentration were uniformly lowest in gross samples from the central and intermediate ischemic zones, and highest in the gross samples from the border normal zone (p less than 0.05). The values for flow and lidocaine in samples from the border ischemic zone were intermediate, that is, higher than values from central ischemic (p less than 0.05) and lower than values from border normal zone samples (p less than 0.05). However, the labeling technique for normal zone tissue revealed that the values of blood flow and lidocaine in the gross samples from the lateral border of the ischemic zone were intermediate between those of adjacent ischemic and normal samples because of the mixture of overlapping normal and ischemic tissues components--not because of a unique mildly ischemic region. Both blood flow and lidocaine concentration were lower in the subendocardial third than in the subepicardial third of the ischemic zone (p less than 0.05) even after the contribution of normal zone tissue was subtracted, suggesting a gradient of ischemia across the transmural border zone. In conclusion, lidocaine is distributed uniformly in ischemic components from the center to the lateral border of the ischemic zone, but there is an endocardial to epicardial gradient. Both lateral and transmural border zone distributions must be considered to understand the mechanisms of drug effects in myocardial ischemia.
Animals↗
Effects of extracellular potassium accumulation and sodium pump activation on automatic canine Purkinje fibres.
1. Double barrel potassium-sensitive micro-electrodes were used to measure fluctuations in extracellular potassium ion concentration in large automatic canine Purkinje fibres.2. Slow accumulations of potassium were seen in the extracellular space during prolonged beating. Following cessation of prolonged beating, a depletion of extracellular potassium ions was noted.3. The time course of these slow changes in extracellular potassium concentration were shown to be a function of the diffusion properties of the preparation, and the rate and degree of activation of the sodium pump.4. Action potential duration and maximum diastolic potential were simultaneously monitored during and after these periods of rapid stimulation, using conventional intracellular micro-electrodes.5. Initial depolarization and later hyperpolarization of the maximum diastolic potential appeared to occur as a direct result of changes in extracellular potassium concentration and level of pump activation induced by the sudden and prolonged alteration in stimulus rate.6. Following prolonged stimulation, dramatic changes in the automatic beating rate were correlated with changes in extracellular potassium and pump rate, and their effects on the maximum diastolic potential and other parameters of the diastolic potential depolarization.7. For some locations of the potassium-sensitive electrode tip, large fluctuations in extracellular potassium were seen during single beats. Alterations in action potential duration during abrupt rate changes appear to derive in part from modulation by these extracellular potassium concentration fluctuations altering net membrane currents. Slower shifts in action potential duration appear correlated to the degree of sodium pump activation.
Action Potentials↗
Epicardial activation in patients with coronary artery disease: effects of regional contraction abnormalities.
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Adult↗
Effects of lidocaine on regional intraventricular conduction in patients with coronary artery disease.
Studies of isolated heart muscle and canine models of myocardial ischemia have demonstrated that lidocaine slows conduction in abnormal but not in normal tissues. To determine lidocaine's effects on intraventricular conduction (IVENT) in patients with coronary artery disease (CAD), we studied this agent in seven patients following left anterior descending coronary artery (LAD) bypass surgery. Epicardial electrodes were placed on the right atrium, left ventricle (LV) in the distribution of the LAD, and on the right ventricle (RV). On postoperative day 7, lidocaine was administered as 100 mg bolus followed by 4 mg/minute infusion for 2 hours. At constant atrially paced rate, bipolar electrograms were recorded from the LV and RV for the 2 hours of infusion and for 2 hours after discontinuation of infusion. Conduction intervals were measured from the earliest onset of QRS in three simultaneously recorded surface ECG leads to the major deflection of the electrogram from each ventricle. At peak effect, with mean lidocaine level of 2.7 +/- 0.5 mg/ml, lidocaine slowed LV conduction by a mean of 6 +/- 1 msec (14 +/- 2%) (p less than 0.001) and in the RV by 1 +/- 0.3 msec (4 +/- 1%) (p less than 0.01), QRS duration changed 1 +/- 1 msec) 1 +/- 1%) (NS). The values returned to baseline within 2 hours after discontinuation of lidocaine infusion. The difference in lidocaine's effect between the diseased LV and the normal RV was significant (p less than 0.001).
Adult↗
Effects of sudden change in cycle length on human atrial, atrioventricular nodal and ventricular refractory periods.
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Adult↗
Activity-dependent extracellular K+ fluctuations in canine Purkinje fibres.
Cardiac Purkinje fibres are important in cardiac electrophysiology and pathology due to their specialized role in the ventricular conducting system, and their properties as a second cardiac pacemaker. Changes in extracellular K+ activity (Ko) affect the conduction velocity and the natural automatic rate of the Purkinje fibre. Both anatomical and electrophysiological studies of the Purkinje fibres have demonstrated the possibility of Ko fluctuations in the narrow intercellular clefts. We investigated using K+ selective electrodes, the effect of the Ko fluctuations observed during activity in canine Purkinje fibres. Summation of Ko fluctuations during single action potentials leads to elevation of baseline Ko during rapid trains. However, unlike in ventricular muscle where depolarization is seen, membrane potential is non-automatic Purkinje fibres hyperpolarizes in response to rapid beating. Prolonged depletions of extracellular K+ following long periods of overdrive are associated with slowly changing membrane currents, which markedly influence automaticity, action potential duration, and membrane potential.
Action Potentials↗
Silent ST segment deviations and extent of coronary artery disease.
Fifty patients who underwent coronary and left ventricular angiography for suspected coronary artery disease (CAD) had ambulatory ECG monitoring at a time remote from that of catheterization. After correcting for positional ST segment variation on ambulatory ECG, the amount of time that ST segments deviated more than 1 mm. from baseline without corresponding angina was determined, and these results were correlated with results of angiography. Silent ST segment deviations were seen in patients without significant CAD in 2.2% of observations, but increased significantly with extent of coronary artery disease (2.9%, 8.2%, and 10.1% of observations in the one-, two-, and three-vessel disease groups, respectively). This relationship was independent of ventricular function, resting ECG, and previous symptoms. It is concluded that silent ST segment deviations on ambulatory ECG reflect the presence and severity of coronary artery disease.
Adult↗
Use of the ambulatory ECG to diagnose coronary artery disease.
Forty-nine patients undergoing cardiac catheterization for suspected coronary artery disease (CAD) were monitored with a two-channel ambulatory ECG and were given maximal treadmill exercise tests when these were not contraindicated. The ambulatory ECG recordings were evaluated for the number of ST segment deviations after correction for positional changes, and the results were then compared with those of the exercise test and coronary angiography. Sensitivity and specificity of ambulatory ECG monitoring for ST segment deviations to detect CAD were 76% and 75% respectively while those of exercise testing were 78% and 63% respectively. Sixteen patients (33% of this series) had equivocal or contraindicated exercise tests and twelve of these patients were correctly classified as to the presence or absence of CAD by ambulatory ECG. ST segment deviations on ambulatory ECG were found in 93% of patients with three vessel, two vessel, or one vessel LAD disease, while exercise testing detected 74% of these patients. Ambulatory ECG is an effective non-invasive method to diagnose CAD and is complementary to excercise testing. It is of special value when the exercise test is equivocal or contraindicated.
Adult↗
Superficial accessory pathway in the Wolff-Parkinson-White syndrome--electrophysiological, surgical and histologic demonstration.
A superficial accessory pathway was demonstrated by electrophysiologic techniques and surgical histopathology in 30-year-old male with Wolff-Parkinson-White syndrome, severe mitral valve disease and medically uncontrollable arrhythmias. In this patient, electrode catheter studies in the cardiac catheterization laboratory revealed antegrade and retrograde function of an accessory pathway between the anterior right atrium and the right ventricle. During surgery, electrophysiologic mapping confirmed the anterior location of this pathway. Blunt dissection in the fat pad of the A-V groove between the right atrium and ventricle revealed the accessory pathway which consisted of tissue strands superficial to the A-V ring. These were removed and on histological examination were composed of ordinary myocardial cells. Concomitant replacement of the patient's calcified stenotic and regurgitant mitral valve was carried out. Postoperatively, there was complete regression of the preexcitation and arrhythmias.
Adult↗
Differing electrophysiologic effects of slow response inhibiting agents manganese and verapamil on ischemic, infarcted and normal tissue in situ.
To determine the electrophysiologic effects of slow response inhibiting agents manganese (Mn) and verapamil, we performed intracoronary infusion of these agents into ischemic, normal and infarcted tissue of canine hearts in situ. We determined intramyocardial conduction intervals, effective refractory period (ERP) and mean femoral arterial pressure. We compared control infusions of isotonic sucrose alone to those in which Mn (0.6 mmol/min) or verapamil (10-20 micrograms/min) was infused into ischemic tissue in the first 10 min after left anterior descending coronary artery ligation. We also studied infarcted tissue 1 hr after coronary artery ligation (Mn only) and normal tissue. During ischemia, Mn delayed conduction intervals in the subepicardium but not in the subendocardium and shortened subepicardial ERP. Mn also increased the occurrence of ventricular fibrillation during ischemia. In infarcted tissue, Mn had no effects on conduction intervals or ERP while in normal tissue it also had no effect on conduction interval but prolonged ERP. Verapamil had no effect on conduction intervals or ERP in ischemic or normal tissue. Neither Mn nor verapamil had any significant effects on mean blood pressure in these studies. Lack of effect of verapamil in ischemic tissue may be explained by the varying and offsetting effects of this drug. Effects of Mn can be explained by slow response occurring during ischemia (when ventricular arrhythmias and increased local potassium concentration occur) in ischemic epicardium but not in endocardium and not when tissue became infarcted (and ventricular arrhythmias have declined). The results are also consistent with our finding that delayed electrical activity in ischemic zones (which may reflect reentrant activity and be associated with arrhythmias) occurred only in subepicardium and not in subendocardium.
Animals↗