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Biomedical subjects

D C Harrison

Publications and source records attributed to D C Harrison.

At least 19 recordsLinked to original sources
PubMed1992

Plaque-associated immune reactivity as a tool for the diagnosis and treatment of atherosclerosis.

In summary, we have confirmed that a specific humoral immune reactivity involves human atherosclerotic plaque. By isolating some of the autoantigens and employing them in prototype immunoassays, we have been able to measure for the presence of plaque-specific antibodies. Extracted plaque antigens have also served as immunogens in monoclonal antibody generation. These have shown early promise as plaque-directed in vivo targeting agents. Further scientific evaluation and reagent development remains before the practical utility of employing such reagents or methods in the care of patients with atherosclerosis-related diseases can be ascertained.

Animals↗
PubMed1991

A pH-dependent phospholipase A2 contributes to loss of plasma membrane integrity during chemical hypoxia in rat hepatocytes.

Previous studies have suggested that alterations in phospholipid composition of plasma membranes may underlie lethal cell injury due to hypoxic and ischemic injury. The present study was designed to determine if such alterations are due to the activation of a pH-dependent phospholipase A2. Loss of cell viability and phospholipase A2 activity measured by arachidonic acid release increased in parallel during metabolic inhibition with KCN and iodoacetate (chemical hypoxia). Acidosis (pH 6.5) and the phospholipase inhibitors, dibucaine and mepacrine, delayed loss of cell viability and release of arachidonic acid to a similar extent. These findings suggest that a pH-dependent phospholipase A2 causes alterations in plasma membrane phospholipid composition after ATP-depletion which contribute to lethal cell injury.

Animals↗
PubMed1990

Histamine mediates myocardial damage by an H1 mechanism independent of coronary blood flow.

Administration of histamine to rabbits may result in myocardial damage similar to that produced by catecholamines and the anthracycline antibiotics. To explore the mechanisms involved in histamine-mediated myocardial damage, conscious New Zealand white rabbits were pretreated with H1 and H2 receptor blocking agents, alone and in combination, and then administered histamine. Coronary artery blood flow was measured with radiolabeled microspheres in rabbits that received histamine alone, and in those that received an H1 blocking agent and histamine. Rabbits that received an H1 blocking agent had a significant reduction in morphological injury which was scored as follows: grade 1, minimal or no injury; grade 2, moderate; and grade 3, severe injury (mean pathology score = 1.1 +/- 0.28 for histamine alone vs. 0.06 +/- 0.06 with H1 receptor blockade, p less than 0.05). Animals pretreated with H2 receptor blockade (mean pathology score = 1.2 +/- 0.49) were not protected against morphological injury. Coronary blood flow decreased in animals that received histamine alone: control = 2.61 +/- 0.38 vs. 1.80 +/- 0.30 ml/min/g (p less than 0.05), and in animals pretreated with H1 blockade; control = 3.29 +/- 0.34 vs. 1.91 +/- 0.28 ml/min/g (p less than 0.01). We conclude that histamine-mediated myocardial damage appears to be mediated by the H1 receptor system and that this appears to be independent of initial changes in global coronary blood flow.

Animals↗
PubMed1989

Arrhythmia prophylaxis after acute myocardial infarction: a decade of controversy.

Primary ventricular fibrillation continues to be a major complication of acute myocardial infarction occurring in 5-9% of patients in the coronary care unit and in a higher percentage of pre-hospital admissions. Prophylactic anti-arrhythmic drugs can prevent primary ventricular fibrillation. Lidocaine has been used for this purpose and can be administered safely and effectively in most patients by following well-established programs based on pharmacokinetic and pharmacodynamic data. The in-hospital mortality for patients with primary ventricular fibrillation exceeds that of matched controls not having the arrhythmia, and many studies show a higher 1-, 3-, and 5-year mortality. Other studies have failed to confirm these long-term results and have produced controversy among cardiologists. I continue to recommend prophylactic antiarrhythmic drugs for all patients with acute infarction, especially in those undergoing early interventional therapy.

Acute Disease↗
PubMed1988

The hemodynamic effects of repeated bed rest exposure.

Hemodynamic changes were measured during stepwise exposure to lower-body negative pressure (LBNP) (5 min, -20, -30, and -40 mm Hg) in a group of seven physically active subjects before and after consecutive exposure to three 2-week bed rest periods. Bed rest exposures were separated by 3-week periods of ambulatory recovery. Dynamic exercise (68% max O2, 30 min each day) and isometric exercise (21% max leg extension, 30 min each day) performed during bed rest and reambulation failed to prevent deconditioning or accelerate the recovery process between bed rest exposures. Heart rate (HR) and end-diastolic volume index (EDVI) proved to be parameters showing greatest changes during LBNP. Heart rate increases at -40 mm Hg LBNP (compared to respective pre-LBNP levels) were 13.3%, 35.1%, and 51.0% for each of the pre-bed rest exposures, while respective changes after bed rest were 57.8%, 57.2%, and 75.5%. The significantly elevated HR responses during subsequent pre-bed rest (control) periods indicated incomplete recovery despite mild exercise and ambulation. Comparison of EDVI and HR revealed a similar linear regression relationship during LBNP before and after bed rest so that EDVI = 112.5-0.85 x HR, r = -0.97. We conclude from these findings that cardiovascular deconditioning for physically active individuals involves factors other than simple loss of plasma volume, requires at least 3 weeks or longer to return to the pre-bed rest state, and is not counteracted by the levels of aerobic and/or isometric exercise used in the present study.

Adult↗
PubMed1987

Pharmacokinetic and pharmacodynamic properties of beta-blocking drugs influencing choice in treatment of systemic hypertension.

Diuretics and beta blockers are the mainstay in treating mild and moderate systemic hypertension, but there is controversy as to which should be used first. Recent evidence of an increase in sudden death and a greater number of intolerable side effects in the diuretic-treated groups in the Multiple Risk Factor Intervention Trial in the U.S. and the Medical Research Council Trial in Great Britain has prompted some to suggest beta blockers as first-line therapy. However, beta blockers also have side effects, such as decreased ventricular function in patients with mild heart failure, increased airways resistance in those with chronic obstructive lung disease, increased plasma lipids, in particular low density lipoprotein cholesterol, and increased problems in patients with peripheral vascular disease and those with diabetes requiring insulin treatment. Many new beta-blocking drugs with different pharmacokinetic and pharmacodynamic properties allow the physician to choose the best one for each patient. beta-blocking drugs with long durations of action, high levels of bioavailability, beta 1 selectivity and intrinsic sympathomimetic activity appear most suitable for therapy. Cardioselectivity is suggested for patients with obstructive lung disease and peripheral vascular disease, and diabetic patients who take insulin. Long durations of action permit infrequent administration and recently agents with intrinsic sympathomimetic activity have been shown to have less effects on plasma lipid levels. Acebutolol also reduces ventricular arrhythmias, and may therefore be used to reduce sudden death in patients with coronary artery disease. The pharmacokinetic and pharmacodynamic properties of beta-blocking drugs can indicate the most appropriate choice for hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
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↗