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Biomedical subjects

D C Harrison

Publications and source records attributed to D C Harrison.

At least 109 records · Page 6Linked to original sources
PubMed1981

Beneficial hemodynamic response to chronic prazosin therapy in congestive heart failure.

Thirteen patients with advanced congestive heart failure (CHF) were treated with prazosin. Following the first dose, cardiac output (CO) (mean +/- SD) rose from 3.2 +/- 1.2 to 4.3 +/- 1.1 L/min, pulmonary artery diastolic pressure (PAD) decreased from 23 +/- 12 to 18 +/- 11 mm Hg, mean arterial pressure (MAP) decreased from 85 +/- 10 to 76 +/- 10 mm Hg, and heart rate did not change (92 +/- 15 vs 92 +/- 14 bpm). At the end of a 48 to 72 hour titration to an optimal regimen, significant effects on CO (3.2 +/- 1.1 vs 4.5 +/- 1.3 L/min), PAD (24 +/- 12 vs 18 +/- 8 mm Hg), and MAP (84 +/- 10 vs 76 +/- 10 mm Hg) were still seen. The patients were restudied after 3 months of treatment. In contrast to reports of rapid development of tolerance to prazosin, we found continued beneficial effects on CO (3.0 +/- 1.3 vs 3.8 +/- 1.0 L/min) and PAD (23 +/- 12 vs 18 +/- 10 mm Hg), without significant change in MAP (81 +/- 11 vs 78 +/- 8 mm Hg). We found wide variability in the CO rise in response to prazosin, which was not accounted for by differences in plasma prazosin concentration. Systemic vascular resistance in the untreated state did correlate with the percentage change in CO. In addition, excessive lowering of the PAD appeared to blunt the CO response in some cases.

Blood Pressure↗
PubMed1981

Platelet activation in clinical coronary artery disease and spasm.

Current concepts of atherogenesis, based on animal models, suggest a role for platelets in the development of atherosclerotic lesions, possibly through the release of alpha granule constituents. Platelets may also contribute to the development of vascular spasm through thromboxane A2 production. Platelet activation in the coronary circulation in patients with coronary artery disease (CAD) should occur if these hypotheses apply clinically. We measured aortic and coronary sinus plasma levels of the platelet alpha granule constituent beta-thromboglobulin (B-TG) and thromboxane B2 (TX B2) by radioimmunoassay in 15 patients with severe atherosclerotic CAD, seven patients with angiographically normal coronaries, and five patients undergoing evaluation for coronary artery spasm (CAS). Compared with the controls, CAD patients had significantly greater transmyocardial release of B-TG (11.1 +/- 8.1 ng/ml, mean +/- SEM vs 62.5 17.2, p less than 0.05 by rank sum test); TX B2 gradients showed a similar trend but the difference was not statistically significant (-0.08 +/- 0.03 ng/ml vs 0.22 +/- 0.02, 0.05 less than p less than 0.10). Three of the five patients studied developed CAS which was associated with acute elevation in coronary sinus TX B2; the two non-CAS patients with drug provocation had undetectable coronary sinus TX B2. We conclude that abnormal platelet activation takes place in the coronary circulation of CAD patients, and that production of acute myocardial ischemia by CAS occurs with increased coronary sinus TX B2.

Angina Pectoris↗
PubMed1981

Electrophysiologic evaluation of encainide with use of monophasic action potential recording.

The electrophysiologic effects of encainide in the intact dog heart were evaluated with the use of monophasic action potential and His bundle recordings. Eight mongrel dogs were given 2.7 mg/kg body weight of encainide in two intravenous infusions. Plasma concentration, blood pressure, surface electrocardiogram, atrial and His bundle electrograms, right atrial and ventricular monophasic action potentials and the right atrial and ventricular effective and functional refractory periods were recorded before and 15 to 45 minutes after each infusion. Basic cycle length and A-H, H-V, QRS and Q-Tc intervals were significantly prolonged after administration of the drug. The refractory periods and the monophasic action potential durations were significantly increased in both the atrium and the ventricle although the increases were more pronounced in the atrium. It is concluded that encainide is a class I antiarrhythmic agent with properties very similar to those of quinidine.

Action Potentials↗
PubMed1981

Coronary artery spasm in the denervated transplanted human heart: a clue to underlying mechanisms.

The mechanism of coronary artery spasm has been poorly understood but there has been some suggestion that cardiac autonomic innervation may play an important role. We report coronary artery spasm in a 43 year old man two years after he had received a transplant. Provocative pharmacologic testing suggested functional denervation of the patient's heart. Thus, coronary artery spasm can occur in the transplanted, denervated human heart. Autonomic innervation of the heart is not essential in all cases of coronary spasm, and circulating catecholamines and/or metabolic of hormonal products may play an important role.

Adolescent↗
PubMed1981

Long-term transtelephonic electrocardiographic monitoring in the detection and evaluation of variant angina.

To facilitate the outpatient diagnosis of variant angina by documenting transient ST segment evaluation during chest pain, we studied the feasibility of transtelephonic ECG monitoring during angina episodes. Eight patients with known coronary artery spasm underwent simultaneous continuous ambulatory and transtelephonic ECG monitoring during a 24-hour period. Five patients (62%) had transient diagnostic ST segment shifts on both continuous ambulatory and transtelephonic monitoring. Another eight patients with coronary spasm underwent 24-hour continuous ambulatory monitoring and separate 14-day period of transtelephonic monitoring. The addition of this longer monitoring period provided diagnostic ST segment shifts in three patients. We conclude that transtelephonic monitoring in patients with suspected coronary artery spasm can provide important additional diagnostic information to continuous ambulatory monitoring, particularly in the patient with infrequent or predictable chest pain.

Adult↗
PubMed1981

Verapamil disposition kinetics in chronic atrial fibrillation.

Verapamil disposition was studied in 12 patients with chronic and fibrillation. After an intravenous bolus of 15 mg plasma concentration was determined and the data fit in a three-compartment model. Model independent parameters were calculated and values for half-life (t 1/2), clearance, and steady-state distribution volume were 6.3 +/- 4 hr, 13.3 +/- 7.7 ml/min/kg, and 4.3 +/- 1.9 l/kg. The model was used to design a multistep infusion scheme, which was employed successfully to achieve predetermined plasma concentrations. Following single oral doses of 120 mg, plasma levels of verapamil and norverapamil were determined. The elimination t 1/2 for verapamil and norverapamil were 8.3 +/- 6.1 and 10.5 +/- 5.6 hr, respectively. The bioavailability of oral verapamil was 35 +/- 16%. During long-term oral therapy the mean verapamil plasma concentration was twice the value predicted from the single-dose studies. This suggests that verapamil may have reduced clearance during long-term oral use.

Administration, Oral↗
PubMed1981

Coronary bypass: the first 10 years.

First by the hundreds, then by the thousands, until today 100,000 coronary bypass procedures are performed in the United States every year! For those patients for whom medical management alone is inadequate, bypass surgery, which has been developed and refined over the years, has proved to be a means not only of prolonging life but, perhaps just as important, of enhancing the quality of that life.

Coronary Artery Bypass↗
PubMed1981

Pathogenesis and prevention of graft arteriosclerosis in an experimental heart transplant model.

Accelerated graft arteriosclerosis is a major cause of death in human heart transplantation. Despite many investigations, the pathogenesis of this disease remains undetermined and its control inadequate. In this study using a rat heart transplant model and cyclosporin A, a new immunosuppressant, acute rejection was prevented but arteriosclerotic-like vessel disease still developed consistently as early as 20 days postoperatively. The combination of cyclosporin A and dipyridamole prevented the development of this vessel disease in transplanted hearts at 20 and 50 days postoperatively. Sulfinpyrazone and cyclosporin A reduced but did not prevent the disease. These findings suggest that immunologically induced graft arteriosclerosis can be prevented in transplanted rat hearts by the combination of cyclosporin A and dipyridamole.

Animals↗
PubMed1981

Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias.

We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness. Nine patients with frequent and complex premature ventricular complexes were studied in a 3-day double-blind protocol. Each day, each patient received 75 mg of i.v. or oral encainide or placebo. Frequent blood samples for encainide plasma concentration determination and continuous ambulatory ECGs were obtained. There was a marked intersubject variation in bioavailability (mean 42 +/- 24%, range 7.4-82%), clearance (13.2 +/- 5.6 ml/min/kg, range 3.75-22.1 ml/min/kg) and half-life (3.4 +/- 1.7 hours i.v., 2.5 +/- 0.8 hours oral). Eight of nine patients had more than 90% suppression of premature ventricular complexes for 3-36 hours. Minimal antiarrhythmic plasma concentration was higher (39 +/- 54 ng/ml, range 3.5-170 ng/ml) after i.v. dosing than after oral dosing (14 +/- 16 ng/ml, range 1.5-48 ng/ml), suggesting an active metabolite after oral dosing in many patients. Minimal side effects were seen despite high peak plasma concentrations (range 794-1556 ng/ml i.v., 36-495 ng/ml oral). The minimal ratio of toxic to therapeutic plasma concentration ranged from 4.3-326 (median 23) after oral dosing. Antiarrhythmic action was associated with an 11-44% widening of the QRS complex that was not associated with other adverse effects. We conclude that encainide effectively suppresses ventricular arrhythmias. Despite a variable bioavailability, high clearance and short half-life, its wide ratio of toxic to therapeutic concentration and probable active metabolite permit a long duration of action, which should allow a reasonable dose schedule in most patients during chronic oral dosing.

Aged↗
PubMed1981

Clinical application of pharmacokinetics for antiarrhythmic drugs.

Tables 3 and 4 summarize the important pharmacokinetic characteristics of commonly-used antiarrhythmic agents. Pharmacokinetic principles are just as important to the clinician as they are to pharmacologists. For the pharmacologist they define the time course of processes involved in the absorption, distribution, metabolism and elimination of drugs. For the clinician they provide basis for administering drugs to patients with disease processes which require a specific agent. Plasma concentration is generally related to efficacy and safety for many antiarrhythmic drugs and understanding the principles related to drug concentration in individual patients is necessary for rational use of many cardioactive agents. This paper provides an approach for the clinician to utilize the basic concepts of pharmacokinetics in practice.

Anti-Arrhythmia Agents↗
PubMed1981

New concepts for antiarrhythmic drugs in the 1980's.

In the 1980's, arrhythmias will be treated with new drugs with increasing efficacy and safety. A better understanding of basic biology will provide the framework for the physician to deal with the problem areas presented. Better chemical techniques for assaying plasma concentration of primary drug and metabolite will provide the clinical basis for administering these new agents. The importance of altered protein binding on both the efficacy and safety of drugs will become better understood. Drug interactions will be appreciated for having both a beneficial and harmful effect in certain patient syndromes. Understanding factors which relate to the bioavailability of a drug will no doubt provide clues as to better administration patterns in most patients. The decade of the 1980's will prove exciting for the clinical pharmacologist and the cardiologist as they treat patients with cardiac arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1981

ECG gating of thallium-201 myocardial images: effect on detection of ischemic heart disease.

Using the angiographic findings as the standard, we have examined the sensitivity and specificity of ECG-gated static thallium-201 myocardial images in 54 patients undergoing selective coronary arteriography. Gated and nongated images, each in anterior, 45 degrees LAO, and 65 degrees LAO projections, were processed by interpolative background subtraction. They were then analyzed separately by four independent observers who were unaware of patient identity, the results of coronary arteriography, and which studies were gated or nongated. No significant differences were observed between the gated and nongated images regarding sensitivity or specificity, the detection rate for reversible myocardial ischemia, the accuracy of prediction of arteriographic extent of disease, or the degree of inter- or intraobserver variability. We conclude that ECG-gated acquisition of T1-201 images does not produce any significant advantages, at least when interpolative background subtraction is used.

Adult↗
PubMed1980

Improved catheter for regional coronary sinus flow and metabolic studies.

An improved coronary sinus catheter has been developed whose enhanced flexibility facilitates catheterization of the great cardiac vein. It allows simultaneous thermodilution measurement of blood flow in the great cardiac vein and proximal coronary sinus, easy withdrawal of blood from both sites and bipolar atrial pacing from the proximal coronary sinus. The accuracy of flow measurement with this catheter has been validated by in vitro testing, and the catheter has been used successfully in eight patients. The advantages of this improved catheter over the existing coronary sinus thermodilution catheter are discussed.

Cardiac Catheterization↗