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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
PubMed1989

Nonsustained ventricular tachycardia arising from the right ventricular outflow tract.

Characteristics of left bundle branch block morphology, inferiorly directed frontal plane QRS axis and repetitive nonsustained salvos were used to define a discrete subgroup of patients with ventricular tachycardia (VT). The origin of this tachycardia was thought to be the right ventricular outflow tract. Twenty-six patients with this definition (group 1) were compared with 29 consecutive patients with all other forms of VT (group 2). When compared with patients in group 2, group 1 patients were younger (average age 37 vs 51 years, p less than 0.005), had less structural heart disease (2 of 26 vs 25 of 29 patients, p less than 0.005) and had a better prognosis (no deaths) after an average follow-up time of 28 months in comparison with 5 deaths after an average follow-up of 35 months (p less than 0.05). Induction of VT was possible using isoproterenol infusion in 14 of 20 group 1 patients, but no VT could be induced in 9 group 2 patients (p less than 0.05). Exercise stress testing induced VT in 11 of 21 group 1 patients and 2 of 9 group 2 patients (p greater than 0.05). Programmed electrical stimulation failed to induce VT in 9 group 1 patients, but did induce it in 15 of 20 group 2 patients (p less than 0.005). Successful therapy in group 1 patients was achieved by beta blockers alone (7 patients), beta blockers plus type 1A antiarrhythmic drugs (9 patients), procainamide alone (2 patients), sotalol (3 patients) and amiodarone (2 patients). Three patients were not treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

In vitro protein binding of propafenone in normal and uraemic human sera.

The protein binding of propafenone, a Class I antiarrhythmic agent, was studied in vitro using a selective and sensitive electron-capture detection gas-liquid capillary chromatographic assay method developed in our laboratory. The concentration-dependency of the serum protein binding of propafenone was confirmed in vitro by equilibrium dialysis, using serum obtained from healthy human subjects and patients with chronic renal failure. In normal serum the unbound fraction of propafenone was 0.027 at a propafenone concentration of 0.25 microgram.ml-1, 0.041 within the therapeutic concentration range (0.5-2 micrograms.ml-1), 0.138 at a propafenone concentration of 25 micrograms.ml-1, and 0.187 when the propafenone concentration was increased to 100 micrograms.ml-1. There was no evidence of significant concentration-dependent changes in unbound fraction within the propafenone concentration range of 0.5-1.5 micrograms.ml-1. However, concentration-dependent binding was demonstrated at concentrations greater than 1.5 micrograms.ml-1. A high-affinity, low-capacity binding site (K1 = 6.53 x 10(5) l.mol-1; n1P1 = 1.73 x 10(-4) mol.l-1) and a low-affinity, high-capacity binding site (K2 = 8.77 x 10(3) l.mol-1; n2P2 = 8.57 x 10(-3) mol. x l-1) were identified. In pooled uraemic serum the unbound fraction of propafenone was approximately 50% of that of normal serum throughout the concentration range studied (1-5 micrograms.ml-1). In sera from patients with chronic renal failure the increase in propafenone binding ratio or the decrease in unbound fraction was associated with the increase in alpha 1-acid glycoprotein concentrations, and there was a correlation (r = 0.8302) between alpha 1-acid glycoprotein concentration and the propafenone binding ratio.

Adult↗
PubMed1989

Atrial pacing: efficacy and safety.

Atrial pacing has the advantages of simplicity, maintenance of AV synchrony, and economy. The major detraction has been the potential for deterioration of atrioventricular conduction. In this study, we followed 43 patients with sick sinus syndrome treated with atrial (AAI) pacing. Excellent initial implant parameters were obtained in all. Three early lead repositionings were required. Minor sensing and pacing problems could all otherwise be handled by reprogramming. Follow-up for a mean of 25 +/- 20 months demonstrated excellent performance of the pacing systems. Pacing and sensing thresholds and lead impedance indicated excellent lead performance. There were no late lead failures. Nine patients have had mild deterioration in atrioventricular conduction and one of these had a change to DDD pacing at the time of elective battery change. All patients are asymptomatic. Thus, chronic atrial pacing in selected patients is safe and reliable with good chronic lead performance and low risk of subsequent conduction system disease.

Adolescent↗
PubMed1989

Impedance to transesophageal atrial pacing: significance regarding power sources.

Transesophageal stimulation is an expeditious method of atrial pacing. Using pulse widths of 10 msec results in reduction of current requirement to values that are usually less than 15 mA. An unknown variable in transesophageal atrial pacing has been impedance. In this study, we investigated the impedance to transesophageal atrial pacing in ten patients using a stimulator with a 63 V power source capable of delivering constant current to 20 mA against an impedance of 2,000 ohms. A bipolar electrode was used to deliver stimuli with a current of 15 mA. Voltage across a known resistance and current were measured on an oscilloscope and the impedance was calculated. Pacing thresholds were also performed and ranged from 6.2 to 16.5 mA (mean 9.4 +/- 2.9 mA, SD). Impedance varied between 720 and 2,670 ohms (mean 1,750 +/- 540 ohms). The stimulator used to measure impedance in man and two other commercially available stimulators were bench tested against known resistances of 500 to 2,000 ohms. The other stimulators with power sources of 12.5 and 15 V had attenuation of the delivered current at resistances of between 1,000 and 2,000 ohms. Thus, this study has demonstrated that transesophageal atrial pacing incurs impedances two to five times greater than incurred with intracardiac pacing leads. Therefore stimulators with high power sources are required to deliver the programmed current against these impedances.

Atrial Function↗
PubMed1989

Effects of acetylcholine, propranolol, and verapamil on sinus node refractoriness of the rabbit.

At a critical premature interval, atrial premature beats encounter sinus node refractoriness and are blocked on entering and fail to reset the sinus node, resulting in interpolation of the premature beat. The transition from reset to interpolated response has been used to define the effective refractory period of the sinus node (SNERP). In an in vitro preparation of rabbit sinus node, we evaluated the effects of acetylcholine, propranolol, and verapamil on SNERP. Results obtained in the control state were compared with those obtained during superfusion with drugs, all of which prolonged refractoriness: acetylcholine from 233 +/- 41 (SD) to 325 +/- 88 ms; propranolol from 215 +/- 60 to 241 +/- 67 ms; and verapamil from 192 +/- 69 to 254 +/- 79 ms (p less than 0.005 with all drugs). The site of block of premature beats was mapped between sinus node and crista terminalis with an intracellular microelectrode. All three drugs resulted in block of premature beats at sites farther from the primary pacemaker site. Thus, acetylcholine, propranolol, and verapamil prolong sinus node refractoriness.

Acetylcholine↗
PubMed1989

The pharmacokinetics of the enantiomers of mexiletine in humans.

1. This study examined the pharmacokinetics of the enantiomers of mexiletine in five healthy subjects who were each given a single, 300 mg, oral dose of racemic mexiletine hydrochloride. 2. The time course of the concentration ratio between the R(-) and the S(+) enantiomers (R/S) in plasma showed a progressive decrease, with a mean +/- S.D. ratio of 1.37 +/- 0.11 at 1 h and 0.64 +/- 0.11 at 48 h. Similarly, the R/S ratios in urine were 1.38 +/- 0.42 and 0.55 +/- 0.12 at 1 h and 72 h, respectively. 3. The terminal elimination half-life of S(+)mexiletine was 11.0 +/- 3.80 h, which was significantly greater (P less than 0.05) than that of the R(-) enantiomer, 9.10 +/- 2.90 h. S(+)Mexiletine also showed a significantly greater apparent volume of distribution (P less than 0.01) and renal clearance (P less than 0.05) than R(-)mexiletine. There was no significant difference in the apparent oral total drug clearance of the enantiomers. 4. The disposition of mexiletine enantiomers in man was stereoselective, and the differences observed between the enantiomers may be due largely to differences in their serum protein binding.

Adult↗
PubMed1988

Effect of pacing cycle length and autonomic blockade on sinus node refractoriness.

Sinus node (SN) refractoriness can be measured indirectly by observing the return responses after the introduction of progressively earlier atrial premature beats. The SN effective refractory period (ERP) is defined as the longest premature interval resulting in an interpolated atrial return response. In the present study, SNERP was analyzed in 71 subjects--51 control persons and 20 patients with evidence of SN dysfunction. SNERP could be measured in 40 of 51 control subjects and was shown to prolong at shorter basic pacing cycle lengths. At a basic cycle length of 600 ms, SNERP was 330 +/- 40 ms, whereas at 500 ms it was 350 +/- 50 ms (p less than 0.05). At a basic cycle length of 600 ms, SNERP was measured in 31 control subjects and 7 patients with SN dysfunction. The values of 330 +/- 40 and 520 +/- 20 ms, respectively, in these 2 groups suggested that this method can be used to differentiate patients with SN dysfunction (p less than 0.001). In 12 control subjects, SNERP was measured before and after partial autonomic blockade with propranolol and atropine. SNERP shortened from 360 +/- 40 to 320 +/- 40 ms (p less than 0.05). It shortened with atropine and prolonged with propranolol. Thus, SNERP prolongs with a shorter basic pacing cycle length and is affected by autonomic manipulation, in a fashion analogous to the atrioventricular node.

Atropine↗
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↗