Search PubMed⌕ Search

Biomedical subjects

D C Harrison

Publications and source records attributed to D C Harrison.

At least 163 records · Page 9Linked to original sources

Measurement of the human magnetic heart vector.

A unipositional lead system has been developed to record the human magnetic heart vector and to permit comparison with the electric heart vector recorded with a conventional Frank lead system. Recordings made in five normal subjects showed a remarkably consistent relation between the electric and magnetic heart vectors. However, the angle between electric heart vector R and T waves was markedly different from the magnetic heart vector R-T angle. In addition, recordings made in two patients with bundle branch block showed a different relation between the electric and magnetic heart vectors compared to normal subjects. These data support the hypothesis that magnetic measurements have a different sensitivity to some components of cardiac activation compared with body surface potential measurements.

Electrocardiography↗

High-pressure liquid chromatographic analysis of drugs in biological fluids. V. Analysis of acebutolol and its major metabolite.

A high-pressure liquid chromatographic analysis for acebutolol and its major metabolite in blood, plasma and urine is reported. The analysis, in which the above mentioned compounds are chromatographed as ion pairs with dodecyl sulfonic acid, uses a simple and rapid method of sample preparation. The technique is more sensitive and rapid than those previously reported and it has equivalent or better reproducibility. The method is applied to the measurement in blood of acebutolol and its acetyl metabolite after a single oral dose.

Acebutolol↗

Hemodynamic changes at the onset of spontaneous versus pacing-induced angina.

To determine the origin of angina pectoris at rest hemodynamic monitoring was performed for 24 to 72 hours in 25 patients with unstable angina who had pacing-induced angina during cardiac catheterization. During the monitoring period, seven patients had spontaneous epidsodes of angina at rest that could be compared with the pain-free periods and periods of pacing-induced angina. At the onset of spontaneous angina, the patients had a significantly lower mean double product (P is less than 0.005) and triple product (P is less than 0.025) than at the onset of pacing-induced angina. The mean double product (heart rate x systolic blood pressure) was 9,411 +/- 2,815 mm Hg/min during pain-free rest, 10,635 +/- 2,587 at the onset of spontaneous angina and 16,623 +/- 3,904 during pacing-induced angina. The mean resting pain-free triple product (heart rate x systolic blood pressure x ejection time) was 3,023 +/- 703 and 3,536 +/- 931 mm Hg/sec per min during, respectively, pain-free rest and spontaneous angina, and 4,350 +/- 938 mm Hg/sec per min during pacing-induced angina. These marked differences in the double and triple products were associated with a mean increase in pulmonary arterial diastolic pressure (from 10.7 mm Hg at rest to 14 mm Hg) at the onset of both spontaneous and pacing-induced angina. Although indirect, these data suggest that transient changes in coronary blood flow, rather than changes in myocardial work, may be primarily responsible for spontaneous angina at rest in certain patients with the syndrome of unstable angina.

Adult↗

Patients admitted to the coronary care unit for chest pain: high risk subgroup for subsequent cardiovascular death.

Approximately 300 persons a year who are admitted to the Stanford University Hospital coronary care unit because of prolong ischemic chest pain and transient S-T changes do not manifest evidence of a myocardial infarction during their hospital stay. In a retrospective study carried out in 170 such patients, follow-up data obtained during a mean of 17.9 months revealed rates of mortality from cardiovascular causes of 4.2 percent for 1 month, 10.1 percent for 1 year and 19.7 percent for the entire follow-up period. Ten (40 percent) of the 23 deaths that occurred were sudden and 13 were due to acute myocardial infarction or its complications. Another 21 patients had a nonfatal myocardial infarction during this follow-up period. The data confirm the impression that patients with suspected myocardial infarction who do not have an infarction in the coronary care unit are at high risk for cardiovascular deaths after hospital discharge. Efforts are under way to define further a high risk subgroup on the basis of clinical indications before discharge.

Adult↗

High-pressure liquid chromatographic analysis of drugs in biological fluids. III. Analysis of disopyramide and its mono-N-dealkylated metabolite in plasma and urine.

A high-pressure liquid chromatographic analysis for disopyramide (I) and its mono-N-dealkylated metabolite (II) in plasma and urine is described. The analysis, in which I and II together with an internal standard are chromatographed as ion pairs with heptanesulphonic acid, employs a simple and rapid method of sample preparation. The method is more sensitive, reproducible, and rapid than previously reported gas chromatographic methods.

Chromatography, High Pressure Liquid↗

Response optimization of drug dosage: antiarrhythmic studies with tocainide.

The benefits of using antiarrhythmic response to optimize dosage regimens of antiarrhythmic drugs in individual patients have been examined. Graded antiarrhythmic response and simultaneously measured plasma drug concentrations have been obtained in 15 patients receiving multiple oral doses of a new antiarrhythmic, tocainide. Plasma drug concentration-antiarrhythmic response data from each of 11 subjects responding to the drug have been fitted by a generalized concentration effect function which is valid over the entire range of response. With the use of experimentally determined pharmacokinetic parameters to define the dose-plasma concentration relationship and plasma drug concentration-response parameters estimated for individual patients, simulations were carried out to show the effect of various dosage regimens on antiarrhythmic response in individual patients. Such simulations provide a means of assessing antiarrhythmic effect in the range of clinical interest (80% to 100% of maximum effect), where the antiarrhythmic effect is a nonlinear function of dose, plasma drug concentration, or their logarithms. The simulations also demonstrate that for identical daily doses and dosing intervals patients show marked variability in antiarrhythmic response.

Administration, Oral↗

Acebutolol disposition after intravenous administration.

The disposition of acebutolol has been studied following intravenous doses of 0.25 to 1.0 mg/kg in 9 healthy subjects using a specific chromatographic assay to determine concentrations of drug in blood. The mean blood clearance was 6.55 ml/min/kg and the mean renal clearance, 2.68 ml/min/kg. Blood clearance was found to have a coefficient of variation of 14% for the group, to be independent of dose, and to remain essentially constant over approximately 3 wk. The fraction of the dose excreted in the urine unchanged was 0.405. Data were fitted to an equation for a two-compartment model. The mean fast and slow half-lives were 6.08 and 156.8 min, respectively. The volume of the central compartment was 0.223 L/kg, and the volume of distribution at steady-state was 1.165 L/kg. The fraction of acebutolol unbound to plasma proteins was 0.743 and was independent of drug concentration in the range examined. Data obtained from 15-min infusions were used to predict plateau blood concentrations with good accuracy during an 8-hr dosage regimen.

Acebutolol↗

High-pressure liquid chromatographic analysis of drugs in biological fluids II: determination of an antiarrhythmic drug, tocainide, as its dansyl derivative using a fluorescence detector.

A sensitive and specific method is described for the determination of a new primary aliphatic amine antiarrhythmic drug, tocainide. Tocainide, together with an internal standard, is selectively extracted from plasma or blood and reacted with dansyl chloride. The highly fluorescent dansyl derivatives are separated using high-pressure liquid chromatography and measured using a fluorescence detector. The method can measure therapeutic and subtherapeutic concentrations of the drug (0.1-5.0 microng/ml of plasma) with a standard deviation of less than 2%.

Anilides↗

Hemodynamic effects of intravenously administered quinidine on the transplanted human heart.

The acute hemodynamic effects of intravenously administered quinidine were studied in five heart transplant recipients with an anatomically denervated heart. Quinidine, 10 mg/kg body weight, was infused over a 20 minute period, and mild wall left ventricular dynamics were measured with a new technique using metallic markers surgically implanted in the myocardial wall. Heart rate was maintained constant with atrial pacing, and aortic blood pressure was measured through an indwelling catheter. In each patient the hemodynamic responses to quinidine were similar. End-diastolic, end-systolic and stroke volumes decreased by an average of 19, 26 and 18 percent, respectively. Cardiac output decreased by a mean 0.92 liters/min (-18%), and the mean aortic blood pressure decreased by 10 mm Hg (-11%). All of these changes were statistically significant. Three indexes of the contractile state of the left ventricle--mean circumferential velocity, mean systolic diameter shortening and ejection fraction--were not significantly changed. We conclude that quinidine exerts no acute inotropic myocardial effects in the human transplanted heart and that, when given intravenously, its hemodynamic action is most consistent with venodilatation.

Blood Pressure↗

Propranolol for patients with mitral valve prolapse.

This study evaluates propranolol's effect on symptoms, arrhythmias, and exercise tolerance in 16 patients with mitral valve prolapse. Three patients (19 per cent) experienced symptomatic deterioration with propranolol therapy, seven (44 per cent) were unchanged, and six (37 per cent) noted an over-all symptomatic improvement, primarily due to a reduction in palpitation. Symptomatic improvement continues in these six patients an average of 12.5 months after beginning propranolol therapy. Treatment with propranolol alleviated chest pain in only two of eight patients and it did not improve the ability to perform treadmill exercise. Fatigue did not improve, and in three patients appeared for the first time during propranolol therapy. Premature ventricular contractions were reduced by at least 75 per cent in five of nin patients (56 per cent), and paroxysmal ventricular tachycardia was eliminated in three of four patients. We conclude that propranolol is not uniformly effective in patients with mitral vale prolapse. A trial of propranolol may be instituted fro patients with mitral valve prolapse who have severe symptoms and/or arrhythmias, but the drug should only be continued in those who demonstrate clinical and/or antiarrhythmic response.

Adult↗

Myocardial imaging in a patient with reproducible variant angina.

A unique case is presented of variant angina pectoris with reproducible chest pain and S-T segment elevation in the immediate postexercise period and with normal coronary arteries. Coronary arterial spasm was deomnstrated with arteriography after intravenous administration of ergonivine maleate. Thallium-201 imaging during the pain reproducibility demonstrated malperfusion in the region supplied by the artery with documented spasm.

Adult↗

Acebutolol metabolite plasma concentration during chronic oral therapy.

1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady-state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/- 1.0. 4 Previous studies using non-specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.

Acebutolol↗

Comparison of dobutamine and dopamine in treatment of severe heart failure.

The haemodynamic effects of dobutamine, a new synthetic catecholamine, were studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine. Dopamine was ineffective in lowering left ventricular end-diastolic pressure, but increased mean aortic pressure. We conclude that dobutamine is an effective, positive inotropic agent in patients with severe congestive heart failure. Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease.

Catecholamines↗

Reproducibility of thallium-201 myocardial imaging.

Seventy-six thallium-201 myocardial perfusion studies were performed on twenty-five patients to assess their reproducibility and the effect ofvarying the level of exercise on the results of imaging. Each patient had a thallium-201 study at rest. Fourteen patients had studies on two occasions at maximum exercise, and twelve patients had studies both at light and at maximum exercise. Of 70 segments in the 14 patients assessed on each of two maximum exercise tests, 64 (91%) were reproducible. Only 53% (16/30) of the ischemic defects present at maximum exercise were seen in the light exercise study in the 12 patients assessed at two levels of exercise. Correlation of perfusion defects with arteriographically proven significant coronary stenosis was good for the left anterior descending and right coronary arteries, but not as good for circumflex artery disease. Thallium-201 myocardial imaging at maximum exercise is reproducible within acceptable limits, but careful attention to exercise technique is essential for valid comparative studies.

Adult↗

Suppression of premature ventricular contractions by acebutolol.

The antiarrhythmic action of the beta-blocking drug, acebutolol, was evaluated in patients with frequent premature ventricular contractions (PVCs). In the 12 hours following administration of a single 300 mg oral dose, 8 of 10 patients showed a greater than 50% reduction in PVC frequency, and statistical analysis indicated that PVC reduction persisted for 10 hours after the single dose. Analysis of plasma concentrations of acebutolol and an acetyl metabolite indicated that after single oral doses of plasma concentrations of the metabolite exceed those of unchanged acebutolol. When patients were studied during periods of 300 mg doses every 8 hours, eight of 11 showed a 70% reduction in PVC frequency, and analysis showed that the therapeutic effect was present throughout the 24-hour monitoring period. Acebutolol slowed the heart rate and prolonged the PR interval without affecting the QT interval. Significant clinical or laboratory toxicity was not encountered. In the small group studied, acebutolol was found to be safe and effective for short-term administration to patients with frequent PVCs and possessed a relatively long duration of antiarrhythmic action.

Acebutolol↗