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Biomedical subjects

D C Harrison

Publications and source records attributed to D C Harrison.

At least 55 records · Page 3Linked to original sources
PubMed1986

Relation of blood level and metabolites to the antiarrhythmic effectiveness of encainide.

Encainide is a potent new antiarrhythmic agent with 2 major active metabolites and 2 distinct phenotypes for metabolism, extensive (approximately 92%) and nonextensive (8%). Encainide is an active compound with close correlation of plasma levels with antiarrhythmic effectiveness and electrocardiographic changes in nonextensive metabolizers. Its metabolites, O-demethyl-encainide and 3-methoxy-O-demethyl-encainide, are active against experimental and clinical arrhythmias. They have longer half-lives than and equal or greater potency than the parent compound. All 3 compounds contribute to the antiarrhythmic profile in extensive metabolizers. There is no readily apparent relation between encainide and its metabolites, blood levels and efficacy because of the complexity of the 3 active compounds and individual variation in pharmacokinetic and arrhythmia responsiveness. Encainide has been given for up to 2 years in 140 patients with sustained ventricular tachycardia or ventricular fibrillation. The survival curves are similar to historical control data from patients reported by Graboys and Swerdlow. The survival curves for long-term administration in patients with frequent ventricular premature complexes (greater than 30/min) are comparable to data from Califf. While these data must be viewed cautiously, it seems fair to conclude that encainide is as effective as any combination of drugs for preventing sudden death in patients with life-threatening ventricular arrhythmias.

Anilides↗
PubMed1986

Effect of the heart-lung boundary on the magnetocardiogram.

Ionic currents flowing during the activation of the heart generate both electric potentials which can be recorded at the body surface as the electrocardiogram or ECG and magnetic fields which can also be recorded at the body surface as what is termed the magnetocardiogram (MCG). In order to apply the MCG to basic research or clinical diagnosis, one must understand the geometric sensitivity of the recorded signals to the cardiac source currents and evaluate the contribution of secondary ohmic body currents relative to the cardiac currents. The present study aims to evaluate the magnitude of the ohmic current contribution by electrically insulating the heart from the body. It is found that volume currents contribute a large part of the MCG signal recorded at distances greater than 10 cm from the heart, but that close to the heart at least one component of the MCG reflects primary cardiac source currents free of interference from volume currents flowing in the body.

Animals↗
PubMed1986

Transvenous coronary angiography in humans using synchrotron radiation.

The risks and costs of the present method of visualizing the coronary arteries have limited the use of coronary angiography in long-term serial studies needed to establish the natural history of coronary atherosclerosis and its response to interventions. A less invasive method, in which the contrast agent is administered intravenously, has been developed using synchrotron radiation as the illuminating source. The present report describes the initial results in human subjects. The findings indicate that transvenous coronary angiograms can be acquired in this manner. Further refinements in the x-ray imaging system are expected to result in increased x-ray fluence and improved image quality.

Angina Pectoris↗
PubMed1986

Valvular-ventricular interaction: importance of the mitral apparatus in canine left ventricular systolic performance.

As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.

Animals↗
PubMed1986

Qualitative and quantitative comparison of the cardiac effects of encainide and its three major metabolites in the dog.

We have evaluated the electrophysiologic effect of encainide and its three major metabolites, O-demethyl encainide, 3-methoxy-O-demethyl encainide and N-demethyl encainide in an anesthetized dog model. Our results support previous reports that O-demethyl encainide and 3-methoxy-O-demethyl encainide are both more potent than encainide in the depression of conduction. We also have shown that N-demethyl encainide is of about equal potency to encainide. Whereas the major differences between these compounds is primarily one of potency, there are some qualitative differences. Although O-demethyl encainide did not change the ventricular or atrial effective refractory periods significantly, 3-methoxy-O-demethyl encainide and N-demethyl encainide prolonged both. Encainide increased the atrial effective refractory period but did not produce significant changes in the ventricular refractory period. These data support previous suggestions of an important role for these metabolites as modulators of the clinical efficacy of encainide.

Anilides↗
PubMed1986

A rational scientific basis for subclassification of antiarrhythmic drugs.

The subclassification of Vaughan Williams Class I agents into IA, IB, and IC groups on empiric and clinical grounds has recently been given a cellular electrophysiologic scientific basis. Based on the kinetics of association and dissociation of the drugs with sodium channels, 3 distinct subgroups can be defined. These observations help to explain the clinical utility of the algorithms to use the agents in patients and provide a reference for discussing the new drugs with antiarrhythmic properties being discovered.

Action Potentials↗
PubMed1985

Cost containment in medicine: why cardiology?

In 1984, expenditures for health care in the United States were nearly $350 billion, more than 10% of the gross national product, and continued increases exceeding the general economic growth are projected. Cardiology and cardiovascular surgery represent a large part of this cost, reflecting the many new diagnostic and therapeutic procedures developed over the past 2 decades. Previous cost containment attempts failed because they provided no incentive to reduce spending for advanced technologies and procedures. A method of payment based on a case mix of 467 diagnosis related groups (DRGs), average duration of hospital stay and location of hospitals has been developed for Medicare. A 4-year trial using this method in New Jersey resulted in lower hospital costs per capita than in the rest of the country. In October 1983, a 3-year phase-in for all Medicare payments by the DRG method began. The 43 DRGs assigned to cardiology and cardiovascular surgery are among the highest-weighted for large reimbursement; thus, with the great number of aging patients with cardiac diagnoses, cardiology represents a very large share of the cost of medical care today. Because the quality of care can be determined and compared directly with costs, cardiology DRGs lend themselves to careful analysis. Three components will be examined. Coronary bypass surgery is the largest single reimbursement, thus the rationale for its use should be carefully studied. Coronary care units have markedly increased hospital costs for acute myocardial infarction, but have also improved care.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiology↗
PubMed1985

Beta blockers and exercise: physiologic and biochemical definitions and new concepts.

Exercise training effects occur in man after chronic exposure to aerobic exercise, which should be defined quantitatively to permit a precise mechanistic understanding. Exercise adaptations result from circulatory and metabolic changes that involve altered responsiveness to neurohumoral transmitters at the receptor level. The adrenergic mechanisms are most important and are linked to new understandings of the adrenergic receptor and its coupling with biochemical processes in the cell. The adrenergic receptor is a specialized protein in the cell membrane linked to the catalytic moiety of the enzyme adenylate cyclase by a coupling protein controlled by guanine nucleotides. The sensitivity of this receptor mechanism may be altered by exposure to agonists and antagonists and by circulatory and metabolic diseases. The effects of beta- adrenergic blockers on exercise adaptation and the clinical sequelae are emphasized.

Adenylyl Cyclases↗
PubMed1985

Exercise training during long-term beta-blockade treatment in healthy subjects.

Although it is well accepted that treatment with beta-blocking drugs impairs endurance exercise capacity acutely, whether a trained state can be achieved while receiving long-term beta-blocker therapy is controversial. The apparent attenuation of training reported in some studies has given rise to the theory that adrenergic stimulation represents a unifying mechanism by which endurance training effects are produced. This theory is supported by studies of long-term beta-agonist infusions that show apparent training responses. To assess the role of beta-adrenergic stimulation produced by exercise in the development of cardiovascular training effects, 39 healthy men were assigned in a random, double-blind fashion to receive oral propranolol, atenolol or matched placebo. Drug doses were titrated individually to minimize the heart rate response to submaximal exercise (dose ranges: atenolol, 50 to 200 mg/day; propranolol, 160 to 320 mg/day). After beginning chronic drug administration, all subjects participated in an intense, supervised 6-week exercise training program (5 days/week, 45 min/day, at least 75% peak heart rate). Adherence to training was monitored by daily supervision; compliance to the medication regimen was assessed by weekly pill counts, medication diaries and plasma drug assay. Maximal exercise testing was performed before and after training. Peak oxygen consumption increased significantly with training in all 3 groups, whether comparisons were made in the presence or absence of medication. The magnitude of change in oxygen consumption did not differ between groups (F = 0.12, p greater than 0.88). Similarly, peak work rate and duration of work increased in all 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Beta blockade in the compensation for bed-rest cardiovascular deconditioning: physiologic and pharmacologic observations.

Beta-adrenergic blockade using intravenous propranolol was evaluated as a countermeasure for bedrest-induced cardiovascular deconditioning. After propranolol administration, tolerance to a maximal lower body negative pressure (LBNP) test after bed rest improved to at least the -70 mm Hg level; following this, there was a sharp decrease in tolerance time. Propranolol decreased mean tolerance time by 36% (17.7 +/- 2.4 to 11.5 +/- 2.3 minutes) before bed rest, and by only half as much (16.6%) after bed rest (14.4 +/- 2.2 to 12.0 +/- 2.3 minutes). Systemic vascular resistance was maintained and even slightly increased after propranolol despite a decrease in cardiac output, indicating beta 2-adrenergic blockade. Heart rates at all levels of LBNP were lower during beta blockade, yet increases occurred with successive LBNP steps, both before and after bed rest, indicating withdrawal of parasympathetic nervous system influences. Results support the use of propranolol in small dosages as a countermeasure after bed rest, and the findings may also be extrapolated to space-flight deconditioning.

Adult↗
PubMed1985

Beta-blocking potency and electrophysiologic effects of acebutolol.

The beta-blocking potency of three doses of acebutolol (100, 200, and 600 mg three times a day) has been compared to that of propranolol (30, 60, and 180 mg three times a day) in a double-blind crossover study in 10 healthy volunteers (seven men, three women). On the basis of reduction in resting and exercise heart rates, propranolol was three to four times more potent than acebutolol on a milligram-for-milligram basis. Plasma levels showed large interindividual variation for both agents. Plasma levels were weakly correlated with the degree of beta blockade for both acebutolol (r = 0.333, p less than 0.001) and propranolol (r = 0.381, p less than 0.01). Dose and percent beta blockade were more strongly correlated (propranolol, r = 0.503, p less than 0.001; acebutolol, r = 0.574, p less than 0.001). In 11 patients (10 men, one woman) with coronary artery disease, acebutolol at 1 mg/kg infused over 15 minutes decreased heart rate and slowed conduction, increased the refractoriness of the atrioventricular node without a significant change in the atrial refractoriness, and at plasma levels greater than or equal to 1000 ng/ml slowed His-Purkinje conduction. The comparative potency data suggest that the magnitude of the decrease in the resting and exercise-induced changes in heart rate and double product, in relation to dose of acebutolol, provides quantitative indices for judging adequacy by beta blockade in clinical therapeutics. The use of plasma drug levels, however, does not appear to be helpful in judging the adequacy of beta blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Acebutolol↗
PubMed1985

Atrioventricular conduction abnormalities in patients undergoing isolated aortic or mitral valve replacement.

Cardiac conduction defects are common in patients with aortic valve disease. Several studies have suggested that the spontaneous occurrence of complete heart block in these patients is related to the extent of calcium deposits in the aortic valve and adjacent structures. No studies have been done to relate the occurrence of complete heart block at the time of valve replacement to predictive factors. We evaluated 102 consecutive patients undergoing isolated aortic valve replacement and 100 patients undergoing isolated mitral valve replacement. Although transient complete heart block was relatively common in each group (17.6% and 13%, respectively), we were not able to identify any factors predictive of its occurrence. There was a very low incidence of late heart block in a follow-up period of over four years. Thus, the capability for temporary pacing is mandatory in patients undergoing valve replacement. However, transient complete AV block during the perioperative period does not predict late recurrence of AV block and, therefore, prophylactic pacemaker or electrode implantation during or following transient block appears unnecessary.

Aortic Valve↗