Biomedical subjects

D M Mirvis

Publications and source records attributed to D M Mirvis.

At least 73 records · Page 4Linked to original sources

PubMed1989

The effects of encainide versus diltiazem on the oxidative metabolic pathways of antipyrine.

The effects of diltiazem and encainide on the pharmacokinetics and metabolism of antipyrine were compared in nine healthy male volunteers. Diltiazem 90 mg every 8 hours for 5 days decreased the oral clearance of antipyrine from 2.34 to 1.86 L/hour (p less than 0.05) and increased half-life from 12.7 to 15.9 hours (p less than 0.05). Diltiazem reduced the formation rate constants for 3-hydroxymethylantipyrine by 27% (p less than 0.05) and 4-hydroxyantipyrine by 37% (p less than 0.05). There was also a 21% reduction in the formation rate constant for norantipyrine (0.05 less than p less than 0.10). Encainide 25 mg every 8 hours for 5 days had no apparent effect on the oral clearance or half-life of antipyrine, or on the formation rate constants for metabolites of antipyrine. In contrast to a previously published report in rats, encainide, unlike diltiazem, does not inhibit the oxidative metabolism of antipyrine in humans.

Adult↗

PubMed1989

Effect of changes in the definition of ventricular tachycardia on the prevalence of complex ventricular ectopy.

The presence of ventricular tachycardia (VT) is commonly considered to represent a risk factor for sudden cardiac death as well as an indication for antiarrhythmic drug therapy. Although spontaneous VT is generally diagnosed by the presence of three or more consecutive ectopic beats, proposed criteria for induced VT require six or more complexes at rates exceeding 90 or 100 beats/min. To determine the clinical implications of a similar change in the diagnostic criteria for spontaneous VT, the authors examined 324 consecutive 24-hour ambulatory electrocardiograms. Of these, 111 (34.3%) had episodes of three or more ventricular premature beats. If six or more beats were required, only 34 (30.6%) would have been diagnosed as having VT. Requiring a minimum rate of 90 or 100 beats/min had less consequence, eliminating only 10 (9.0%) and 12 (10.8%) patients, respectively. Patients with only three to five beat runs had significantly fewer isolated premature beats (4,462.8 +/- 588.4 vs 7,158.1 +/- 1,688.1) and ventricular couplets (186.2 +/- 39.2 vs 294.3 +/- 74.4) per day, and slower average rates (142.1 +/- 4.6 vs 171.8 +/- 6.7 beats/min) during ventricular tachycardia than did those with runs of six or more beats. Thus, altering the definition of spontaneous VT has marked effects on the prevalence of this arrhythmia. Those patients excluded did, however, have a lower prevalence of associated electrocardiographic risk factors.

Anti-Arrhythmia Agents↗

PubMed1989

Pacemaker therapy for academic medicine.

Both the clinical practice and the administrative environments of academic medicine have become progressively more complex. Although management methods for dealing with the administrative intricacies are commonly not part of academic training, guidelines may be derived from medical practice. The authors identify specific parallels and analogies between recent developments in the design of pacemakers and the requirements of organizations that implant them.

Academic Medical Centers↗

PubMed1989

Procainamide N-acetyltransferase: modulation by clofibrate and a microsomal form.

1. Detoxification of procainamide by N-acetyltransferase which occurs primarily in the cytoplasmic fraction of the rat liver can be modulated by clofibrate treatment. 2. When the concentration of one of the substrates, procainamide, is 100 microM while the other, acetyl CoA, is 10 or 100 microM, the specific activity is reduced following clofibrate treatment. However, total activity is unchanged because of a 44% increase in cytoplasmic protein. 3. At more physiological levels of the two substrates (10 microM), total enzyme activity is increased from 9.5 +/- 1.5 to 14.0 +/- 1.8 pmol/mg/min, P less than 0.05. 4. A microsomal form of N-acetyltransferase activity is reported which is unaffected by the concentration of acetyl CoA in contrast to the cytoplasmic form.

Acecainide↗

PubMed1989

Dose effects of adenine on myocardial ATP content in the post-anoxic nonworking rat heart.

1. Tissue ATP levels were measured in Langendorff perfused nonworking rat hearts subjected to 50 min anoxia prior to reperfusion with Krebs-Ringer bicarbonate (KRB) buffer alone or supplemented with 50 microM or 1 mM adenine for 60 min. 2. ATP content was restored to the normoxic range in hearts reperfused with 50 microM adenine in KRB (20.82 +/- SEM 1.90 mumol/g dry weight vs 24.95 +/- 0.83 in normoxic hearts, P = NS). 3. Reperfusion with oxygenated KRB alone or buffer with 1 mM adenine failed to improve ATP levels (17.23 +/- 0.91 mumol/g dry weight for buffer alone, 15.60 +/- 0.46 with 1 mM adenine and 13.45 +/- 0.93 for anoxic hearts not reperfused). 4. These findings indicate that adenine at 50 microM dosage can restore ATP concentrations to the normoxic range after 60 in of anoxia in the nonworking rat heart while raising the adenine dose to 1 mM inhibited the tissue ATP content.

Adenine↗

PubMed1989

The effect of diltiazem on the disposition of encainide and its active metabolites.

The disposition of encainide is under genetic control. In extensive metabolizers, the drug undergoes extensive first-pass metabolism to form the active metabolites O-desmethylencainide (ODE) and 3-methoxy-O-desmethylencainide (MODE). Because diltiazem is a known inhibitor of hepatic oxidative metabolism, the disposition of encainide and its metabolites was studied in eight extensive metabolizers and one poor metabolizer before and after administration of 90 mg diltiazem every 8 hours for 10 days. After diltiazem, the encainide serum AUC values increased in seven of the eight extensive metabolizers, and the percent recovery of encainide in urine increased by 69%. There were no apparent changes in the serum AUC values of the metabolites, suggesting that diltiazem may alter both the formation and the elimination clearances of the metabolites to a similar degree. In the poor metabolizer, encainide serum AUC increased 33% during treatment with diltiazem, but ODE and MODE could not be reliably quantitated. The subjects had no change in QRS, QTc, or JTc intervals after administration of diltiazem. Diltiazem inhibited the first-pass metabolism of encainide, resulting in increased bioavailability. This appeared to be caused by the inhibition of debrisoquin 4-hydroxylase and impairment of other unmeasured metabolic pathways for encainide. However, because no change occurs in the systemic exposure to the active metabolites, dosage adjustments in extensive metabolizers are probably not required for patients receiving combination encainide and diltiazem therapy.

Adult↗

PubMed1989

A multicenter study of the safety and efficacy of benazepril hydrochloride, a long-acting angiotensin-converting enzyme inhibitor, in patients with chronic congestive heart failure.

Benazepril hydrochloride is a nonsulfhydryl, long-acting angiotensin-converting enzyme inhibitor that is orally effective. This study was designed to determine the acute hemodynamic effects of this agent in patients with chronic congestive heart failure. Twenty-six patients with New York Heart Association class III or IV congestive heart failure and left ventricular ejection fractions less than 35%, cardiac indexes less than 2.1 L/min/m2, and pulmonary artery wedge pressures greater than 12 mm Hg were given 2 or 5 mg benazepril hydrochloride. All does produced significant (p less than 0.05) increases in cardiac output (26.7% to 31.6% above control) and heart rate (5.4% to 11.2% above control) and decreases in systemic (27.1% to 32.0% below control) and pulmonary (34.8% to 55.5% below control) vascular resistances, mean pulmonary (25.3% to 30.3% below control) and systemic (13.4% to 18.5% below control) arterial pressures, and pulmonary artery wedge pressure (46.9% to 51.1% below control). Twenty-four hours after an initial dose, systemic vascular resistance and pulmonary artery wedge pressures remained below control levels. Angiotensin-converting enzyme activity fell by 67.8% +/- 6.4%, with a 15.8% +/- 7.6% decline in aldosterone levels. Thus benazepril hydrochloride is an effective angiotensin-converting enzyme inhibitor that produces hemodynamic effects that persist for 24 hours after a single oral dose.

Adult↗

PubMed1989

Instrumentation and practice standards for electrocardiographic monitoring in special care units. A report for health professionals by a Task Force of the Council on Clinical Cardiology, American Heart Association.

The proposed recommendations for continuous electrocardiographic monitoring systems represent goals for future development. Description of a technique in the report does not constitute an endorsement of its clinical use. Lead systems for ECG monitoring must adequately sense the cardiac electrical field and the leads should be standardized. Future monitors should be capable of simultaneously displaying and analyzing multiple leads. Recommendations for electrode placement and position of patient are made. Important parameters in each category of standards for instrumentation published in 1983 in the American National Standard for Cardiac Monitors, Heart Rate Meters, and Alarms are listed. Selected procedures proposed by the Association for the Advancement of Medical Instrumentation to inform users of minimally acceptable accuracy of computerized systems in a standardized manner are presented. Emphasis is placed on the importance of nursing and medical staff capabilities. Personnel qualifications and training as well as systems to assure and maintain quality of immediate ECG diagnosis are highlighted.

Allied Health Personnel↗

PubMed1988

Comparative electrocardiographic and myocardial blood flow effects of rapid atrial pacing and dipyridamole infusion in dogs with chronic coronary artery occlusion.

Altering regional myocardial flow by the use of potent vasodilators as well as increasing oxygen demand by exercise have been employed as diagnostic methods for detecting coronary arterial obstruction. We sought to define the relative capabilities of these two methods to produce abnormal ECG patterns and to alter myocardial blood flow after Ameroid constriction of the left circumflex coronary artery. Atrial pacing to rates of 210 beats/min was performed, followed by intravenous administration of 0.25 and 0.50 mg/kg of dipyridamole. ECGs were recorded to construct body surface isopotential distributions. Flow was measured by serial injections of radiolabelled microspheres. In 15 animals studied after 3 to 5 weeks of Ameroid constriction, pacing increased epicardial flow by 19.14 +/- 7.11% but reduced endocardial flow by 35.69 +/- 12.32%, with a significant reduction (to less than 0.67) in the endocardial/epicardial flow ratio in 12 (80%) dogs; both endocardial and epicardial flows were significantly lower in the ischemic than in the nonischemic bed. Ten dogs developed abnormal ST segment responses of subendocardial ischemia. In contrast, dipyridamole produced a dose-dependent rise in both endocardial (25.33 +/- 8.54% and 55.80 +/- 9.22% after 0.25 and 0.5 mg/kg, respectively) and epicardial (29.13 +/- 7.49% and 66.33 +/- 7.64% after 0.25 and 0.5 mg/kg, respectively) flows without a significant fall in the transmural ratio. These increases were, however, significantly less than those observed in nonischemic bed flow, resulting in a transventricular gradient of blood flow. No dog developed abnormal ECG patterns after dipyridamole infusion. Thus pacing produces both a transmural and a transventricular gradient in blood flow, whereas vasodilation causes only a transventricular flow abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Physiologic bases for anterior ST segment depression in patients with acute inferior wall myocardial infarction.

Patients with acute inferior myocardial infarction commonly have ST segment depression in the anterior precordial leads. This may reflect either reciprocal changes from the inferior ST elevation or primary ST depression from additional anterior subendocardial ischemia. From a biophysical perspective reciprocal changes should be uniformly anticipated from basic dipole theory. Detection will vary with the size, location, orientation, and electrical intensity of the lesion and with the ECG lead system deployed to register the anterior changes. Alternatively, acute occlusion of the right coronary artery may produce ischemia in the anterior left ventricular wall supplied by a stenotic anterior descending coronary artery. Anterior ischemia may result from the abnormal hemodynamics or the reduced collateral flow produced by acute right coronary artery occlusion. Thus both mechanisms are based on sound physiologic principles. A review of the clinical literature suggests that such patients represent a heterogeneous group. In some instances coexistent anterior ischemia is present, whereas in others the anterior ST depression is the passive reflection of inferior ST elevation augmented in many cases by a large infarct size or more extensive posterobasal or septal involvement.

Animals↗

PubMed1988

Effects of residual stenosis on infarct size and regional transmural myocardial blood flow after reperfusion.

This study in dogs was designed to determine the effects of residual stenosis on infarct size and on the transmural distribution of coronary flow in the central and peripheral ischemic perfusion bed. A plastic shunt containing a Doppler flow probe was inserted between the left anterior descending coronary artery and the subclavian artery. The dogs were divided into two groups. Group 1 (N = 7) underwent total shunt occlusion for 2 hours followed by reperfusion at 50% of control flow for 2 hours. Group 2 (N = 8) underwent 2 hours of total occlusion followed by 2 hours of total reperfusion. Regional blood flow was measured by radiolabeled microspheres, and infarct areas were quantitated with triphenyl tetrazolium chloride staining. Infarct sizes expressed as a percentage of the left ventricle or as a percentage of perfusion territory were significantly (p less than 0.05) smaller in animals with total reperfusion (group 2) than in dogs with partial reperfusion (group 1). Endocardial flows in the central infarct zone were significantly higher in dogs with total reperfusion than was observed with partial reperfusion; epicardial flows were not significantly different. In the peripheral region both endocardial flows and epicardial flows with total reperfusion were significantly higher than with partial reperfusion. These studies suggest that residual stenosis after thrombolysis may increase infarct size and reduce endocardial flow in the central infarct zone and transmural flow in the peripheral zone.

Animals↗

PubMed1988

Efficacy of pentoxifylline in patients with stable angina pectoris.

Pentoxifylline, a methyl xanthine derivative, improves symptoms of peripheral vascular disease probably by reducing whole blood viscosity. The authors assessed the value of this agent in treating myocardial ischemia in 11 patients with angiographically documented coronary artery disease and stable angina pectoris. Maximal, symptom limited treadmill exercise stress tests were performed before and after six weeks of therapy with 1200 mg of pentoxifylline per day. Clinical symptoms proved in 9 [82%] of patients; none developed drug side effects. After therapy, mean total exercise time [7.7 +/- 1.3 vs 10.1 +/- 1.2 minutes], time to onset of angina [5.5 +/- 0.9 vs 7.9 +/- 1.0 minutes], heart rate at onset of angina [93.4 +/- 6.7 vs 112.0 +/- 10.5 beats/min] and rate at onset of ST depression [94.0 +/- 5.8 vs 115.9 +/- 7.4 beats/min] all increased significantly [p less than 0.05]. Mean maximum ST segment depression also decreased [1.6 +/- 0.3 vs 1.2 +/- 0.4mm], but the difference was not significant. Thus, pentoxifylline increases exercise performance in patients with angina pectoris and increases exercise capacity before development of of myocardial ischemia. It may, therefore, be a useful agent for treating ischemic heart disease.

Adult↗

PubMed1988

The effect of cigarette smoking on the pattern of coronary atherosclerosis. A case-control study.

Cigarette smoking is a risk factor for development of coronary atherosclerosis. We examined the relationship between smoking and the anatomic location of coronary artery stenosis in 8,705 patients undergoing cardiac catheterization for suspected coronary artery disease (CAD). The smoking history of patients with CAD (greater than or equal to 70 percent stenosis) was compared with that of control subjects (0 percent stenosis) for each of nine anatomic locations (proximal, middle, and distal segments of right [RCA], anterior descending [LAD], and circumflex arteries [LCX]), using a case-control method. The odds ratio (OR) estimate of relative risk of CAD for smokers relative to nonsmokers was 2.8, with a 95 percent confidence interval (CI) of 2.5 to 3.1. Relative risk was greater for RCA stenosis (OR = 5.8; CI = 4.6-7.2) than for LCX (OR = 3.5; CI = 2.7-4.5) or LAD (OR = 2.1; CI = 1.8-2.4) lesions when comparing smokers with nonsmokers. After control for age, gender, history of diabetes mellitus, and serum cholesterol level, the adjusted relative risk for an RCA lesion (Mantel-Haenszel odds ratio [MOR] = 4.9) was significantly elevated (p less than 0.05) compared with the LAD (MOR = 1.9) but not with the LCX (MOR = 3.1). The relative risks of CAD were the same (p greater than 0.05) for the proximal, middle, and distal coronary segments. Thus, smoking increased the risk of all coronary lesions but did so more for the RCA than for other vessels, suggesting a spatial pattern to the increased risk produced by smoking.

Adult↗

PubMed1988

Postmenopausal estrogen use and coronary atherosclerosis.

STUDY OBJECTIVE: To determine whether estrogen replacement therapy affects the prevalence of severely obstructive coronary arterial lesions defined by selective coronary arteriography. DESIGN: Case-control study. SETTING: Large, urban, university-affiliated referral hospital. PATIENTS: From a consecutive sample of 6452 women having coronary arteriography between 1972 and 1984, 2188 patients were eligible for study; others were excluded because they were nonmenopausal, had congenital heart defects, valvular heart disorders, primary myocardial disease, or no more than mild to moderate coronary artery disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital nurses routinely obtained medication histories. Staff invasive cardiologists interpreted coronary arteriograms. Clinical, laboratory, and angiographic data were abstracted from the cardiac catheterization reports and entered into a computerized registry. Postmenopausal estrogen use for 1444 cases of coronary artery disease (70% stenosis) was compared to that 744 controls (0% stenosis). The odds ratio estimate of the risk of coronary artery disease for estrogen users relative to the risk of coronary artery disease for nonusers was 0.44 (95% confidence interval, 0.29 to 0.67) after adjustment for age, cigarette smoking, diabetes, cholesterol, and hypertension. Postmenopausal estrogen replacement was a significant independent protective factor for coronary artery disease in a multivariate logistic regression model (P = 0.037). CONCLUSION: The data suggest that postmenopausal estrogen treatment reduces the risk for angiographically significant coronary artery disease.

Age Factors↗

PubMed1988

Effects of chronic phenobarbital on verapamil disposition in humans.

Very little is known about the effects of hepatic enzyme induction with phenobarbital on the disposition of high clearance drugs in humans. Our study was undertaken to investigate the effect of phenobarbital on both alpha-1 acid glycoprotein concentrations and total and free verapamil and its metabolites. Single oral, single i.v., and multiple oral verapamil administrations were evaluated before and after 21 days of phenobarbital treatment in healthy caucasian male volunteers. Significant changes in the pharmacokinetics of total and free verapamil and its metabolites occurred in a predictable manner. Mean total apparent oral clearance after a single dose of verapamil was increased after phenobarbital treatment (75.1 +/- 49.2 vs. 376.2 +/- 221.8 ml/min/kg, P less than .05). Clearance of free drug increased to a similar magnitude. Mean total verapamil systemic clearance was increased (9.95 +/- 1.3 vs. 18.9 +/- 8.7 ml/min/kg, P less than .05); however free drug clearance was not altered. After multiple oral administration, total verapamil apparent oral clearance was increased after phenobarbital pretreatment (21.2 +/- 9.8 vs. 91.2 +/- 28.5 ml/min/kg, P less than .05). Free drug clearance was increased similarly. Finally, the pharmacokinetic theories derived for hepatic extraction of drugs subject to a high metabolic clearance can be successfully applied to men after liver enzyme induction with phenobarbital.

Adult↗

PubMed1987

Association between the severity of diabetes mellitus and coronary arterial atherosclerosis.

The relation between the severity of diabetes mellitus (DM) and the risk of significant coronary artery lesions were studied in 7,655 patients undergoing coronary arteriography for suspected coronary artery disease (CAD) between 1972 and 1982. The principal treatment regimen for DM was used to estimate the severity of DM. DM treated with insulin was defined as the most severe (n = 244), followed by DM treated with oral agents (n = 344) and with diet only (n = 380); 6,687 patients did not have DM. Severity of DM in patients with CAD (70% or greater diameter stenosis) was compared with that in control subjects without CAD (0% stenosis) for each of 9 anatomic locations (proximal, middle and distal portions of right, anterior descending and circumflex coronary arteries) using a retrospective case-control approach. The risk of CAD was highest in patients with DM treated with insulin (odds ratio estimate of the relative risk [OR = 3.0]), followed by patients with DM treated with oral agents (OR = 1.8) and lastly in those treated with diet alone (OR = 1.4). Severity of DM was a significant (p less than 0.05) independent predictor of CAD in a multivariate logistic regression model, whereas age at onset and duration of DM were not. The relative risk of CAD was the same (p greater than 0.05) for each of the 9 coronary segments. The data suggest that the risk of CAD increases with the severity of DM, which was a stronger predictor of CAD than duration of DM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Nonlinear pharmacokinetics of unbound propranolol after oral administration.

After multiple oral doses, propranolol has been reported to accumulate to a greater degree than expected based on its terminal elimination rate constant and dosage interval. To determine whether the decrease in presystemic elimination can be attributed solely to a decrease in unbound intrinsic clearance or possibly a decrease in unbound fraction, we studied the pharmacokinetics of unbound propranolol in nine healthy subjects who were given 160 mg of regular or sustained-release propranolol orally as single doses, and once daily for 7 d. Unbound propranolol concentrations were calculated by HPLC and equilibrium dialysis on each serum sample. With regular propranolol, the mean unbound oral clearance (CLoral) decreased 29%, from 503 +/- 281 after a single dose to 359 +/- 143 mL/min/kg at steady state (p less than 0.05). Similarly, CLoral decreased 33% with sustained-release propranolol from 1077 +/- 514 to 721 +/- 385 mL/min/kg (NS). The corresponding accumulation ratios for regular and sustained-release propranolol were 1.39 +/- 0.49 and 1.61 +/- 0.81, respectively (NS). Therefore, the mean bioavailability of sustained-release relative to that of regular propranolol was 0.52 +/- 0.23 and 0.54 +/- 0.17 for single doses and at steady-state, respectively. The percent unbound of propranolol ranged from 6.8 to 14.0 with an average of 10.1. Neither the percent unbound nor alpha 1-acid glycoprotein (AAG) serum concentrations were statistically different between single and multiple doses. The binding ratio was significantly correlated to AAG concentration (r = 0.776, p less than 0.05). The data support a decrease in unbound intrinsic clearance of propranolol with no change in unbound fraction, leading to an increase in bioavailability at steady state.

Administration, Oral↗

PubMed1987

Propranolol pharmacokinetics and pharmacodynamics after single doses and at steady-state.

The duration and extent of cardiac beta-blockade and their relationship to propranolol pharmacokinetics were assessed in nine healthy volunteers. Each subject received 160 mg of regular propranolol (R), 160 mg of sustained-release propranolol (SR) and no drug (control), both as single doses and once daily for 7 days. After single doses and at steady-state, both products caused a decrease in exercise heart rate for at least 24 h, compared to control. The time course of effect was similar to the time course of serum propranolol concentration. The oral clearance of propranolol decreased from single doses to steady-state for both R and SR; however, the difference achieved statistical significance only for R. These changes were reflected in mean accumulation ratios (AUC steady-state 0-24 h/AUC single dose 0-infinity) of 1.49 and 1.68 for R and SR, respectively. The pharmacokinetic data are consistent with a decrease in intrinsic hepatic clearance of propranolol, leading to an increase in bioavailability at steady-state. Despite a two-fold difference in the bioavailability of R and SR, there was no difference in the area under the effect-time curve at steady-state.

Administration, Oral↗