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Biomedical subjects

F I Marcus

Publications and source records attributed to F I Marcus.

At least 19 recordsLinked to original sources
PubMed1992

Dissociation of atrioventricular conduction and refractoriness following application of radiofrequency energy to the canine atrioventricular node: acute and chronic observations.

The electrophysiology of AV nodal modification induced by radiofrequency energy (n = 5) or a sham procedure (n = 5) was studied in ten dogs. The five dogs that received radiofrequency energy had an AH prolongation > 100% from baseline values and this prolongation persisted throughout the 2-month study. The AV nodal functional refractory period was prolonged only acutely. These data indicate a dissociation between the effects on AV nodal conduction and refractoriness that was induced by this procedure. The five sham treated controls showed no acute or chronic electrophysiological changes. In the dogs that received radiofrequency energy, there was fibrosis of the approaches to the AV node and the region of the AV node itself. It is concluded that chronic modification of AV nodal conduction without concomitant changes in refractoriness can be induced by radiofrequency energy delivered in the proximal portion of the AV node. It would be anticipated that this procedure would not decrease the ventricular response to atrial fibrillation or flutter, may be effective in preventing AV nodal reentrant tachycardia by interfering with conduction either in the AV node or perinodal region. Since the AV node itself suffers at least moderate pathological damage, there may be an appreciable incidence of the late development of complete heart block after this procedure.

Animals↗
PubMed1992

Evaluation of electrocardiographic leads for detection of atrial activity (P wave) in ambulatory ECG monitoring: a pilot study.

The usual lead systems for ambulatory ECG monitoring (AECG) used in the evaluation of arrhythmias is a modified bipolar V-1 and V-5. A comparison of various lead systems to enhance the detection of atrial activity (p waves) has not been reported. We evaluated various surface lead systems in 12 subjects comparing p waves recorded at 20 mm/mV and 50 mm/sec. We compared p wave area, amplitude, and duration from modified bipolar V1 and V5 as well as seven nonstandard leads recorded on a AECG monitor. Of the seven nonstandard leads, a vertical sternal lead, with the negative pole just below the suprasternal notch and the positive pole at the xiphoid process, had the largest area (1.46 +/- 0.65 mm2), and also had a greater area than the standard V1 (0.88 +/- 0.45 mm) and V5 (1.06 +/- 0.49 mm2) lead system (P less than 0.01). We conclude that the bipolar vertical sternal lead system provides a larger p wave area than seven nonstandard bipolar lead systems and the two standard lead systems currently used in AECG monitoring. Replacement of the modified bipolar V1 lead with a vertical sternal lead should improve the recognition of atrial activity and, therefore, enhance the diagnosis of cardiac arrhythmias.

Adult↗
PubMed1992

Drug combinations and interactions with class III agents.

Drug combinations with class III antiarrhythmic agents have not been studied systematically. There are data indicating that enhanced efficacy as evaluated by electrophysiologic studies can be obtained by combining sotalol and a type Ia drug or amiodarone with low-dose beta-blocking drugs. Combining amiodarone with a type Ia or Ic drug or with a beta-blocking drug can slow the rate of ventricular tachycardia to make the ventricular tachycardia hemodynamically well tolerated. Pharmacokinetic drug interactions with amiodarone are extensive. Recently, it has been shown that hepatic metabolism of amiodarone can be induced to enhance the conversion of amiodarone to N-desethylamiodarone. The physiologic effect of this drug transformation is uncertain. There should be few pharmacokinetic drug interactions with sotalol because this drug is almost completely absorbed, does not bind to plasma proteins, and is excreted unchanged by the kidneys.

Amiodarone↗
PubMed1979

Digoxin-quinidine interaction Pharmacokinetic evaluation.

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.

Digoxin↗
PubMed1979

Electrocardiographic axis deviation in Navajo and Apache indians.

It has been our clinical impression that the range of the mean frontal-plane electrocardiographic QRS axis was greater than might have been anticipated in healthy Navajo and Apache Indians. To determine whether this clinical impression was correct, electrocardiograms were obtained from 146 Navajo, 144 Apache, and 159 non-Navajo non-Apache schoolchildren with normal findings on cardiovascular examinations. A mean frontal-plane QRS axis between -1 degrees and -90 degrees was present in 19 percent of the Navajo, 12 percent of the Apache, and 2 percent of the control schoolchildren. A mean frontal-plane QRS axis between +91 degrees and +180 degrees was present in 18 percent of the Navajo, 19 percent of the Apache, and 5 percent of the control schoolchildren. There is a high incidence of electrocardiographic mean frontal-plane QRS axis deviation in healthy Navajo and Apache schoolchildren.

Adolescent↗
PubMed1978

Relationship between plasma concentration and dose of digoxin in patients with and without renal impairment.

The purpose of this study was to determine if there is a linear relationship between oral doses of digoxin and various measurements of steady-state digoxin plasma concentration and urinary excretion in patients with wide range of renal function. Ten patients (mean age 58 years) with creatinine clearances greater than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 80 ml/min/1.73 m2 BSA) and nine patients mean age 61 years) with creatinine clearances less than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 20 ml/min/1.73 m2 BSA) were given digoxin tablets orally at two or three different dose levels (dose range 0.0313--0.5 mg/day). After a dosing period equal to at least five half-lives, three to four consecutive daily digoxin plasma concentrations were determined. Plasma concentrations and urinary digoxin excretion were measured during one 24-hour dosing interval at each dose level. Digoxin plasma and urine concentrations were determined in triplicate using radioimmunoassay. Individual patient plots provided evidence of linearity for: digoxin 24-hour steady-state plasma concentration vs dose; digoxin 24-hour cumulative urinary excretion versus dose; and area under the digoxin plasma concentration-time curve during a 24-hour dosing interval vs dose. Absolute values for these various parameters indicated substantial interpatient variation probably due to patient differences in both digoxin absorption and digoxin total body clearance. These results indicate that there is a linear relationship between digoxin plasma concentration and dose in patients with normal and decreased renal function. This linearity is support for dose-independent pharmacokinetics of digoxin in man. We conclude from these data that a change in digoxin dose should result in a proportional change in digoxin plasma concentration over the dose range examined.

Administration, Oral↗
PubMed1978

Digoxin disposition kinetics in dogs before and during azotemia.

The purpose of this study was to evaluate the disposition kinetics of digoxin after the administration of a single intravenous dose to the same dogs before and during azotemia. The digoxin plasma concentration-time data were fitted to a multicompartment model using nonlinear regression analysis. During azotemia, the biological half-life of digoxin was prolonged in six of seven dogs, while digoxin renal clearance, body clearance and apparent volume of distribution were significantly decreased. There was a corresponding increase in the apparent volume of the "central" compartment of digoxin. Approximately 45% of a digoxin dose was excreted by the kidney in these animals indicating a substantial nonrenal component to digoxin elimination in the dog. This nonrenal elimination did not change during azotemia, despite a decrease in renal clearance by 61%.

Animals↗
PubMed1977

The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man.

Seven subjects who underwent jejunoileal bypass surgery for massive obesity participated in a study to examine the relative bioavailability of digoxin before and one to two months after surgery. They were given a loading dose of 1 mg digoxin in divided oral doses followed by oral maintenance doses of 0.5 mg daily. There were no significant differences in the area under the serum concentration time curve, steady state serum levels or 24 hour steady state excretion of digoxin before and after surgery. We conclude that the bioavailability of digoxin from the Lanoxin tablets employed is not impaired in these patients, although urinary d-xylose and 24 hour fecal fat excretion indicated moderate to severe malabsorption after surgery.

Digoxin↗
PubMed1976

Digoxin bioavailability: formulations and rates of infusions.

The bioavailability of digoxin (lanoxin) tablets, oral aqueous solution of digoxin, and capsules containing a solution of digoxin was compared with digoxin given intravenously over 1 and 3 hr. The mean peak serum concentration of digoxin after the 1-hr intravenous infusion was 5 ng/ml, after the 3-hr infusion, 3.5 ng/ml, and after the oral solution, 2.0 ng/ml. There was an equivalent bioavailability of the oral solution and reference tablets of digoxin. The digoxin in capsules tended to be better absorbed than the reference tablets. There was 21% more digoxin excreted over 6 days after the 3 hr iv infusion than after the 1 hr iv infusion. This indicates that the calculated bioavailability of an orally administered dose of digoxin may vary with the rapidity of injection of the intravenous standard. It is estimated that an oral tablet of digoxin of 0.5 mg has about the same bioavailability as 0.35 of digoxin given by slow intravenous infusion (or 0.4 mg if calculated against a rapid intravenous injection).

Administration, Oral↗