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Biomedical subjects

C R Kerr

Publications and source records attributed to C R Kerr.

At least 55 records · Page 3Linked to original sources
PubMed1988

"Nodoventricular" accessory pathway: evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties.

Two patients are described with recurrent pre-excited tachycardia and electrophysiologic characteristics typically ascribed to a nodoventricular accessory connection. The accessory pathway in each case demonstrated rate-dependent prolongation of conduction time and a low right ventricular insertion site; it was associated with a left bundle branch block configuration during pre-excitation. Intraoperatively, the pathway was demonstrated to originate at the anterior right atrioventricular (AV) anulus and not at the AV node. These data suggest that a "typical" nodoventricular pathway, by electrophysiologic criteria, may in fact be an AV pathway with AV node-like conduction properties and a distal right ventricular insertion site.

Adult↗
PubMed1988

Surgical therapy for sinoatrial reentrant tachycardia.

Sinoatrial reentry is an uncommon cause of paroxysmal supraventricular tachycardia. This paper presents a case of supraventricular tachycardia, refractory to medical therapy, in which the sinus node formed part or all of the reentrant circuit. The mechanism of the arrhythmia was confirmed by catheter mapping during electrophysiological study and by intraoperative epicardial mapping. Cryosurgical ablation of the right atrium in the region of the sinus node has led to cure of her arrhythmia and emergence of a stable ectopic atrial pacemaker rhythm.

Adult↗
PubMed1987

Determination of propafenone in biological fluids by fused-silica capillary gas chromatography using electron-capture detection.

A gas-liquid chromatographic method with electron-capture detection using a capillary column with the inlet in the splitless injection mode is reported for the assay of propafenone. A 25 m X 0.31 mm cross-linked, 5% phenylmethylsilicone-coated fused-silica capillary column was employed for all analyses. The present method provides improved selectivity and sensitivity over other existing gas chromatographic and high-performance liquid chromatographic (HPLC) methods. Linearity was observed in the ranges 2.5-50 and 10-100 ng/ml. The coefficient of variation was found to be less than 10% over the concentration ranges studied. Application of the developed method is demonstrated by measuring serum propafenone concentrations over 24 h in a normal healthy volunteer after a single oral dose of propafenone and by measuring trough plasma propafenone concentrations at steady state in patients receiving this new antiarrhythmic drug. Validity of the present method is further demonstrated by comparison of analytical results obtained from measurement of patient samples using a modified published HPLC method.

Acylation↗
PubMed1987

Stereoselective analysis of the enantiomers of mexiletine by high-performance liquid chromatography using fluorescence detection and study of their stereoselective disposition in man.

A sensitive, stereoselective high-performance liquid chromatographic assay was developed for the resolution of the enantiomers of mexiletine as their 2-naphthoyl derivatives on a Pirkle type 1A chiral phase column. Detection of the derivatives was accomplished with a fluorescent detector. Maximum recovery of the enantiomers from plasma was 83% and was observed when plasma proteins were precipitated with a mixture of barium hydroxide-zinc sulphate. The calibration curve in plasma was linear over the concentration range 5-750 ng/ml for each enantiomer (r2 = 0.999) and in urine the linear range was 0.25-7.5 micrograms/ml (r2 = 0.999) for each enantiomer. The minimum detectable quantity of each enantiomer in plasma was 5 ng/ml at a signal-to-noise ratio of 5:1, representing 100 pg injected. A preliminary pharmacokinetic study was undertaken in one healthy male volunteer following an oral dose of 300 mg of racemic mexiletine hydrochloride. The apparent elimination half-lives determined from the plasma data were 12.1 and 14.1 h for the R(-) and S(+) enantiomers, respectively. The cumulative urinary excretion amounts of R(-)- and S(+)-mexiletine were found to be 8.01 and 10.46 mg, respectively. The plasma data indicated that a cross-over of the enantiomer ratios occurred at approximately 8 h. The urinary excretion of the enantiomers was consistent with the pattern found in plasma.

Chromatography, High Pressure Liquid↗
PubMed1987

Food increases the bioavailability of propafenone.

The effect of food intake on the bioavailability of propafenone, a new antiarrhythmic agent, was evaluated by comparing its kinetics in 24 healthy volunteers in a fasted state and after a standard breakfast. With food, the maximum plasma drug concentration was reached earlier and was significantly increased. When data from 'slow' metabolizers were excluded, there was an average increase of 147% in the area under the concentration-time curve (AUCo) following the standard breakfast. There was a significant correlation (r = 0.946) between [(AUCo fed - AUCo fasted)/AUCo fasted] and propafenone intrinsic clearance in the fasted state. Food intake, however, does not appear to affect the bioavailability of propafenone in 'slow' metabolizers. Patients should be advised to take propafenone in a constant relationship to food to assure consistent bioavailability.

Adult↗
PubMed1987

Disopyramide pharmacokinetics and metabolism: effect of inducers.

1. The disposition of orally administered disopyramide was studied in a population of smokers (n = 6) and non-smokers (n = 8) before and during phenobarbitone treatment (100 mg daily for 21 days; Cp 21st day = 13.9 +/- 2.0 micrograms ml-1). The comparative inducibility of these populations by phenobarbitone was assessed as was the inductive effect of cigarette smoking, per se. Furthermore, the determinants of the intensity of the inductive effect were examined, as well as the effect of the barbiturate on the binding of disopyramide to alpha 1-acid glycoprotein (AGP). 2. Smokers and non-smokers exhibited similar half-lives (6.48 +/- 1.49 vs 6.66 +/- 1.02 h), apparent total body clearances (0.100 +/- 0.020 vs 0.117 +/- 0.034 l h-1 kg-1), mean renal clearances (0.043 +/- 0.0093 vs 0.057 +/- 0.013 l h-1 kg-1) and apparent intrinsic metabolic clearances (0.057 +/- 0.015 vs 0.060 +/- 0.024 l h-1 kg-1) before phenobarbitone treatment. 3. Both populations responded comparably to barbiturate exposure in that apparent intrinsic metabolic clearance more than doubled. Interestingly, the magnitude of this increase was highly dependent on the observed baseline apparent intrinsic metabolic clearance, (r' = 0.81; P less than 0.001). 4. Phenobarbitone treatment of non-smokers resulted in an increase in the AUC of the active metabolite N-despropyl disopyramide (MND), but not significantly (3.8 +/- 1.6 vs 4.1 +/- 2.3 micrograms ml-1 h). Similar results were observed in smokers (3.5 +/- 1.4 vs 3.9 +/- 2.0 micrograms ml-1 h, respectively). 5. The percent of administered dose recovered in urine as disopyramide in non-smokers was significantly decreased upon phenobarbitone treatment (43 +/- 6% vs 25 +/- 5%), whereas the percent of dose recovered as MND increased significantly in this group (25 +/- 6% vs 31 +/- 5%). The population of smokers responded similarly. 6. At doses typically used to achieve hepatic microsomal enzyme induction in man, phenobarbitone treatment caused no significant change or trend towards a change in serum AGP concentrations as measured using the radial immunodiffusion method in nonsmokers (67.4 +/- 19.9 mg dl-1 vs 68.0 +/- 40.7 mg dl-1) or smokers (64.5 +/- 15.7 vs 67.9 +/- 14.9). Similarly, when AGP concentration was estimated in serum from non-smokers using a nephelometric method no effect attributable to phenobarbitone was observed (47.9 +/- 1.3 vs 47.9 +/- 16.8 mg dl-1). Consistent with this observation, disopyramide free fraction was not affected by barbiturate treatment.

Adult↗
PubMed1987

Termination of spontaneous atrial flutter by transesophageal pacing.

Transesophageal atrial pacing using the constant-rate technique was performed in 26 patients presenting with spontaneous atrial flutter (atrial cycle length between 180 and 270 ms). All but one patient had been treated with one or more antiarrhythmic agents (digoxin, quinidine, procainamide, propranolol, verapamil, diltiazem, and propafenone) within the previous 12 hours. Transesophageal atrial pacing at cycle lengths between 80 and 180 ms was successful in terminating atrial flutter in 22 patients: immediate reversion to sinus rhythm in 16, following transient sinus pause in one, following a brief period of atrial fibrillation in three, and following longer periods of atrial fibrillation in another two. No post-conversion ventricular arrhythmia and no other complications were observed. All patients experienced only a mild burning discomfort during the procedure. It is concluded that atrial pacing via the esophagus is a safe and noninvasive technique of terminating spontaneous atrial flutter. The effectiveness of this technique is comparable to endocardial or epicardial atrial pacing.

Adolescent↗
PubMed1987

Stereoselective serum protein binding of mexiletine enantiomers in man.

The binding of mexiletine enantiomers to human serum proteins was studied in vitro using serum samples collected from five healthy male subjects. Racemic mexiletine was added to an aliquot of each subject's serum to cover the concentration range 0.2 to 2.0 micrograms/mL. Following ultrafiltration of the serum samples containing racemic mexiletine, the individual enantiomers were determined using a stereoselective high-performance liquid chromatographic method developed in our laboratory. The assay data thus obtained for the free levels of the enantiomers showed that the free fraction of S(+) mexiletine was 28.32 +/- 1.45% and that of the R(-) enantiomer was 19.80 +/- 1.49%. The binding was shown to be significantly greater (p less than 0.001) for R(-) mexiletine than its antipode. There was no evidence of concentration dependence in binding over the concentration range studied, which covered the normal therapeutic range. However, significant inter-individual variability in the free fractions was observed. The total binding of the enantiomers was 76%.

Blood Proteins↗
PubMed1986

Transvenous atrial pacing in the management of sick sinus syndrome following surgical treatment of the univentricular heart: case report and review.

An 11-year-old boy with univentricular heart type A-III underwent surgical treatment at age 10 with a modified Fontan operation. Six months postoperatively he developed intermittent periods of cyanosis and fatigue associated with profound sinus bradycardia and nodal escape. After demonstrating normal atrioventricular conduction, a transvenous atrial pacemaker was implanted. This produced a marked clinical improvement. Transvenous atrial pacing is a satisfactory method of treating sinus node dysfunction in patients with univentricular heart following the Fontan operation provided that there is normal AV conduction.

Child↗
PubMed1986

Improved transesophageal recording and stimulation utilizing a new quadripolar lead configuration.

Transesophageal pacing and recording are valuable techniques in the diagnosis and treatment of patients with arrhythmias. Bipolar pacing with bipolar catheters has been effective, but recording from the same electrodes is not possible during and immediately following pacing. We utilized a fine no. 4 French quadripolar catheter in 21 subjects to stimulate the atrium and record atrial electrical activity simultaneously. Pacing characteristics were equivalent to previously used bipolar catheters and recording was markedly enhanced. Bipolar atrial electrograms could be recorded either during pacing or at the first atrial depolarization following pacing in all patients. Thus, this quadripolar pacing lead improves the diagnostic value of studies involving transesophageal atrial pacing and recording.

Arrhythmias, Cardiac↗
PubMed1985

Effect of basic pacing cycle length on sinus node refractoriness in the rabbit.

The effect of basic pacing cycle length on sinus node refractoriness was investigated. In 18 rabbit right atrial preparations, the sinus node effective refractory period (SNERP) was measured at multiple basic pacing cycle lengths. In 14 experiments SNERP was measured at basic pacing cycle lengths of 400, 350 and 300 ms. The mean SNERP (+/- standard deviation) prolonged from 168 +/- 31 ms at 400 ms to 181 +/- 37 ms at 350 ms to 196 +/- 40 ms at 400 ms (p less than 0.001). To rule out the possibility that rapid stimulation might release acetylcholine and thus prolong refractoriness, 4 more experiments were conducted in the presence of atropine (2 X 10(-6) M), and similar results were obtained. The spatial orientation of refractoriness was examined in 7 experiments. At the same premature interval, shorter basic pacing cycle lengths resulted in block of the premature impulse at a greater distance from the sinus node. Therefore, in sinus node tissue refractoriness increases with shortening of basic pacing cycle length, a response similar to that of the atrioventricular node.

Action Potentials↗