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Biomedical subjects

C R Kerr

Publications and source records attributed to C R Kerr.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

Incidence and clinical significance of accelerated junctional rhythm following open heart surgery.

Accelerated junctional rhythm following open heart surgery may lead to hemodynamic impairment due to loss of synchronized atrial contraction. Therefore, in this study we evaluated the frequency, duration, and hemodynamic effects of accelerated junctional rhythm in 30 patients undergoing coronary artery bypass (CAB) and in 30 undergoing valve replacement (VR). Accelerated junctional rhythm was defined as a rate greater than 55 bpm. Patients were continuously monitored postoperatively and rhythm strips obtained at least every 4 hours. Ten VR patients (33%) and four CAB patients (13%) exhibited accelerated junctional rhythm, the difference between these groups being significant (p less than 0.02). Nine of the 14 were hemodynamically compromised requiring inotropic support (9) and/or pacemaker insertion (2). The time of appearance of accelerated junctional rhythm ranged from immediate to 6 days (mean 26 +/- 52 hours, SD) and it lasted a mean of 16 +/- 22 hours. The rate ranged from 62 to 150 bpm. The sinus rate prior to the onset of accelerated junctional rhythm was significantly lower than the sinus rate in those not developing accelerated junctional rhythm. In conclusion, accelerated junctional rhythm is seen frequently following open heart surgery and may lead to hemodynamic deterioration. It is seen more frequently following VR, in approximately 33% of patients. Its manifestation appears to result from a combination of acceleration of junctional focus and slowing of sinus node discharge.

Coronary Artery Bypass↗

Amplitude of atrial electrical activity during sinus rhythm and during atrial flutter-fibrillation.

The onset of atrial flutter or fibrillation in a patient with a DDD pacemaker may result in sensing of the atrial arrhythmia and an inappropriate ventricular pacing response. In order to assess the potential of this problem, we evaluated the amplitude of atrial electrograms recorded from the right atrial appendage during sinus rhythm and during atrial flutter or fibrillation during 19 episodes in 18 patients. In 11 episodes of fibrillation and eight episodes of flutter, there was no difference in amplitude of either unipolar or bipolar atrial electrograms compared to that recorded during sinus rhythm (p greater than 0.05). In 14 of 19 episodes, the direction of depolarization of the bipolar electrogram did not change appreciably between sinus rhythm and the atrial arrhythmia. In summary, there is insufficient difference between amplitude of atrial depolarizations recorded during sinus rhythm and atrial flutter or fibrillation to be differentiated reliably by DDD pacemakers.

Adult↗

Transvenous atrial pacing following amputation of the atrial appendage at open heart surgery.

The right atrial appendage is frequently amputated at the time of open heart surgery. In this study we report implantation and chronic follow-up pacing data on 17 patients in whom either actively fixated screw-in leads or passively fixated tined "J" leads were implanted into the trabeculae at the base of the atrial appendage. Chronic follow-up demonstrated excellent chronic pacing thresholds and atrial sensitivity thresholds in those patients in whom these measurements could be made. It is therefore concluded that satisfactory atrial pacing can be achieved in patients who have previously undergone amputation of the atrial appendage during open heart surgery.

Adolescent↗

Microvascular pressure, surface area, and permeability in isolated hindquarters of SHR.

The transvascular escape rate (TER) of labeled albumin is reported to increase in essential hypertension. However, the mechanism for this augmented rate of protein efflux is uncertain and may be related to increased microvascular permeability, surface area, and/or pressure. To determine the possible contributions of these mechanisms to increased TER of protein, the osmotic reflection coefficient for total plasma protein, capillary filtration coefficient, and effective capillary pressure were estimated in isolated hindquarters of age-matched (12-13 wk) spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WR) rats. Estimates of the reflection and filtration coefficients were not significantly different in SHR, WKY, and WR. However, capillary pressure was significantly greater in SHR than in normotensive controls. These results indicate that 1) skeletal muscle microvascular permeability and surface area are similar in SHR, WKY, and WR; 2) effective capillary pressure is greater in SHR than WKY or WR; and 3) if TER for protein is elevated in hypertensive skeletal muscle, the primary mechanism for this process may be increased convective transport of protein secondary to elevated microvascular hydrostatic pressure.

Animals↗

Use of electrical pacemakers in the treatment of ventricular tachycardia and ventricular fibrillation.

Significant advances have been made in the therapy of ventricular arrhythmias. Many new antiarrhythmic drugs have expanded the medical armamentarium to treat ventricular tachycardia and ventricular fibrillation, and the use of intracardiac electrophysiologic studies has aided in predicting long-term drug efficacy. Major advances have also been made in the surgical treatment of arrhythmias. However, there remain a number of patients in whom ventricular arrhythmias remain a major therapeutic problem and, in some of these, electrical devices may aid in treatment. Overdrive pacing may prevent certain cases of ventricular arrhythmias, and antitachycardia devices may be useful in terminating paroxysmal ventricular tachycardia. In certain circumstances, internal cardioversion or defibrillation may be an alternative. At present, antitachycardia pacing and internal countershock must be considered as forms of therapy to be used when medical and surgical therapy are impractical or have failed. Careful selection is necessary to delineate patients in whom these forms of therapy may be indicated.

Cardiac Catheterization↗

Applicability of capillary gas liquid chromatography to the measurement of free fraction of disopyramide in human plasma.

A sensitive and specific capillary gas liquid chromatographic nitrogen/phosphorus selective detection technique was used to measure unbound disopyramide in human plasma. The concentration dependent protein binding of disopyramide was examined. Various concentrations of disopyramide alone ranging from 0.5 to 10.0 micrograms/ml in 0.4 ml of isotonic phosphate buffer (pH 7.4) were dialyzed for 6 hours at 37 degrees C, against 0.4 ml blank plasma from five healthy volunteers. The concentration-dependent binding of disopyramide was confirmed. The average free fraction for disopyramide at concentrations of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0 and 10.0 micrograms/ml were 0.14, 0.15, 0.20, 0.27, 0.30, 0.34 and 0.53, respectively.

Chromatography, Gas↗

Simultaneous quantitation of disopyramide and its mono-dealkylated metabolite in human plasma by fused-silica capillary gas chromatography using nitrogen-phosphorus specific detection.

A nitrogen-specific detector gas-liquid chromatographic assay method is reported which provides improved selectivity and sensitivity for disopyramide and its mono-N-dealkylated metabolite using a crosslinked fused-silica capillary column. The quantitation of disopyramide and mono-N-dealkylated disopyramide was accomplished by injecting trifluoroacetic anhydride-treated samples containing derivatized internal standard p- chlorodisopyramide , into a gas chromatograph equipped with a nitrogen--phosphorus detector and an automatic liquid sampler. A 25 m X 0.31 mm crosslinked, 5% phenylmethyl silicone-coated fused-silica column was utilized and samples were injected using the splitless injection mode. Linearity was observed in the range 0.05-5.00 micrograms/ml for disopyramide and 0.02-3.00 micrograms/ml for the mono-N-dealkylated metabolite. The coefficient of variation was found to be within 10% for both compounds in the concentration range studied.

Chromatography, Gas↗

Morphine-halothane interaction in rats.

The effects of morphine, halothane, and their various combinations on the purposeful movement (PM) response and the heart rate (HR) increase caused by noxious stimulation were studied in 250 rat experiments. Doses that block the PM and HR responses for the single agent and for combinations were determined with a probit procedure and compared with an isobolographic analysis. As was evidenced by the PM response, the combined anesthetic effect of morphine and halothane, with some deviations, may be defined as additive. It also was found that the combined administration of morphine and halothane results in an antagonism for suppression of the HR increase to noxious stimulation. Halothane antagonized morphine to a much greater extent than morphine to halothane.

Animals↗

Failure to pace following high dose antiarrhythmic therapy--reversal with isoproterenol.

A patient with resistant ventricular tachycardia treated with a combination of antiarrhythmic agents is described. Sudden onset of a wide complex ventricular rhythm with periods of asystole and failure to achieve transvenous pacing were observed, presumably due to antiarrhythmic drug toxicity. Inability to pace was reversed by the infusion of isoproterenol.

Amiodarone↗