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Biomedical subjects

A Broughton

Publications and source records attributed to A Broughton.

At least 37 records · Page 2Linked to original sources
PubMed1987

Induction of ventricular arrhythmias by programmed ventricular stimulation: a prospective study on the effects of stimulation current on arrhythmia induction.

A protocol for programmed ventricular stimulation is described in which the effect of increasing stimulation current on ventricular refractoriness and arrhythmia induction was specifically examined. The protocol was evaluated prospectively in 70 patients undergoing electrophysiological study for documented or suspected ventricular arrhythmias. Programmed electrical stimulation was performed at the right ventricular apex and outflow tract using single and double extrastimuli and burst pacing. Stimulation currents of 2, 5, 10, and 20 mA were used in ascending order. The initial (lowest) current was never less than twice diastolic threshold and was maintained during each stimulation run until refractoriness was reached. The current was then increased to the next level to facilitate premature capture until refractoriness was encountered at 20 mA or a sustained arrhythmia occurred. Ventricular arrhythmias were induced in 34 patients, 31 of whom had presented with a sustained ventricular arrhythmia. The incidence of induced arrhythmias was low in those patients who had presented with symptoms alone, a non-sustained arrhythmia, or a sustained arrhythmia in association with a predisposing clinical event. Only one patient with a negative result had further ventricular arrhythmias during the mean follow up period of 15 months. Although each increase in stimulation current caused a decrease in measured ventricular refractoriness, this resulted in only four arrhythmias. Only one arrhythmia was induced above 5 mA. These results suggest that this simple protocol using two extrastimuli and a single stimulation current of 5 mA will reliably identify most patients who have symptomatic ventricular arrhythmias.

Adolescent↗
PubMed1987

A new approach to the identification of pathogenetic factors and to therapy in human primary hypertension.

In experimental studies on renovascular hypertension, we found that the amplifier properties of the hypertrophied heart and resistance vessels contributed considerably more to the maintenance of the elevated blood pressure (BP) during the chronic phase of the disorder than the basic underlying cause. This must also occur in chronic primary hypertension. Accordingly, we hypothesized that after reversal of hypertrophy by antihypertensive medication, the cause(s) of hypertension should be easier to detect during the redevelopment of hypertension once medication was stopped than in the chronic phase of the disorder. We have studied three groups of patients with moderate/severe hypertension in whom BP was controlled for 1 month; 1 year; 15 months to 5 years. The rate of subsequent redevelopment of hypertension between the series was inversely related to the duration of therapy, which was mostly with beta blockers and diuretics. The differences in the rate of redevelopment of hypertension between series 2 and 3 suggest that, with the drugs used, reversal of vascular hypertrophy is quicker than reversal of left ventricular hypertrophy (LVH). In series 3, we observed an inverse relationship between LV mass and duration of therapy. Redevelopment of hypertension was slowest after obtaining regression of both vascular hypertrophy and LVH. Preliminary findings suggest that sympathetic overactivity is present during the redevelopment phase in the majority of patients. Our findings have suggested a new therapeutic strategy, where the effectiveness of nonpharmacological methods of controlling BP is enhanced by first causing regression of cardiovascular hypertrophy by drug treatment followed by a non-drug phase of maintaining normal BP. We have found moderate regular exercise one of the most effective nonpharmacological antihypertensive methods and have now maintained five patients with moderate hypertension at normal BP for 1 year, following an initial period of drug treatment.

Animals↗
PubMed1986

Left ventricular pump function in renal hypertensive dogs with cardiac hypertrophy.

We compared open-chest left ventricular (LV) pump performance after autonomic blockade under controlled loading conditions in normal dogs and in dogs where chronic renovascular hypertension had produced moderate concentric LV hypertrophy (LVH). Mean LV pressure (MLVP) provided a measure of ventricular load independent of vascular properties. We found an inverse relationship between MLVP and cardiac index (CI) in both groups when peripheral resistance was altered at constant left atrial pressure. However, CI declined significantly less in LVH hearts as MLVP was increased. The slope of the linear MLVP-CI plot (LV source resistance) was 1.91 times the value observed in normal dogs. LVH hearts developed more steady-flow external power than their normal counterparts, and the power optimum was reached at a much higher mean arterial pressure. Isovolumic maximum rate of LVP rise was 1.28 times higher in LVH than normal dogs (P less than 0.01) in proportion to the increase in wall thickness. Our results suggest that additional muscle with normal contractile properties and greater emptying due to the increased wall-to-lumen ratio accounted for the increased pump performance in LVH.

Animals↗
PubMed1985

Influence of buffers on dV/dtmax recovery kinetics with lidocaine in myocardium.

Buffers are reported to modify electrical function of heart tissue. Since electrophysiological actions of antiarrhythmic drugs are examined in different buffer systems, we set out to examine the influence of buffers on lidocaine's electrophysiological actions by measuring recovery kinetics of maximum upstroke velocity (dV/dtmax) in lidocaine solutions buffered with HCO-3-CO2, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), and tris(hydroxymethyl)aminomethane (Tris) at extracellular pH 7.4. Transmembrane potential and dV/dtmax were recorded from guinea pig papillary muscle. Recovery kinetics were determined by introducing progressively earlier test stimuli during diastole. During lidocaine (1.5 X 10(-5) M) exposure, the time constant (Tr) of dV/dtmax recovery significantly increased when 21 mM HCO-3-5% CO2 was replaced by either 5 mM HEPES (38 +/- 8%, mean, +/- SED) or 5 mM Tris (41 +/- 6%). This potentiation of Tr was 1) reversed by increasing Tris to 20 mM, and 2) also abolished by restoring HCO-3-CO2 to HEPES or Tris solutions. Decreasing HCO-3 (21-4 mM) and CO2 (5-1%) increased Tr by 27 +/- 1%. We propose that the mechanism for the potentiation of Tr is therefore related to buffer concentration rather than to the lack of HCO-3-CO2. We speculate that, by reducing surface pH, lowered buffer capacity can slow the rate of dV/dtmax recovery.

Action Potentials↗
PubMed1984

Lipid solubility modulates pH potentiation of local anesthetic block of Vmax reactivation in guinea pig myocardium.

Current theories envision recovery from local anesthetic block of sodium channels via slow hydrophilic and fast hydrophobic paths. Extracellular pH reduction which increases cationic/neutral anesthetic form should especially prolong recovery kinetics of highly lipid soluble compounds that could readily exit via the hydrophobic pathway at normal extracellular pH. To test this hypothesis, we compared the effects of three related compounds with similar pKa on the time course of Vmax reactivation in guinea pig papillary muscle at pHo 7.4 and 6.95. The compounds were lidocaine and its two desethylation products, monoethylglycinexylidide and glycinexylidide. Judged from the octanol:water partition coefficient, lidocaine was the most lipid soluble (log partition coefficient 2.39 +/- 0.10), followed by monoethylglycinexylidide (log partition coefficient 1.32 +/- 0.09) and glycinexylidide was the least lipid soluble (log partition coefficient 0.41 +/- 0.09). At 30 microM and pHo 7.4, the potency order for Vmax depression at zero diastolic interval was lidocaine (53 +/- 6%), monoethylglycinexylidide (17 +/- 3%), and then glycinexylidide (7.8 +/- 1.9%). The decay of Vmax block appeared monoexponential, and the time constant of recovery was dose independent. Most important is the fact that there were significant differences in the tau r increase with extracellular pH reduction (P less than 0.05; Scheffé contrasts). The increase was greatest with lidocaine [73 +/- 28% (mean +/- SD)], less with monoethylglycinexylidide (42 +/- 15%), and least with glycinexylidide (13 +/- 17%). The simplest interpretation of the differences in extracellular pH-dependence of recovery kinetics was that recovery from block due to the neutral form of these ionizable local anesthetics depended on lipid solubility, whereas recovery from block due to the protonated form depended on molecular weight.

Action Potentials↗
PubMed1983

Differentiation of septal from free wall accessory pathway location: observations during bundle branch block in reciprocating tachycardia in the presence of type I antiarrhythmic drugs.

In patients with Wolff-Parkinson-White syndrome, observations during bundle branch block (BBB) in reciprocating tachycardia are of value in accessory pathway localization. Most importantly, an increase in the ventriculoatrial (VA) interval of greater than or equal to 35 ms has indicated an ipsilateral free wall location and excluded a septal location. The present study examined whether data collected in the presence of type I antiarrhythmic drugs retained localizing value. Review of retrospective data showed that observations in the drug-free state were precluded by the need to suppress atrial arrhythmia during electrophysiologic study in 20% of patients with Wolff-Parkinson-White syndrome who underwent preoperative workup. Prospectively, in 15 patients with left free wall or posteroseptal pathways, we observed transient left BBB during tachycardia before and after administration of procainamide, disopyramide or quinidine. Serum drug levels ranged from 4.6 to 6.9 mg/liter, except in 1 patient with a serum procainamide level of 18 mg/liter. Drugs increased the VA interval during narrow QRS tachycardia by 17% (p less than 0.01). However, the change in the VA interval with left BBB was not significantly affected. The baseline and drug values averaged 73 ms (range 39 to 94) and 70 ms (range 39 to 90), respectively, for left free wall pathways (n = 8), and 19 ms (range 0 to 28) and 21 ms (range 2 to 35), respectively, for posteroseptal pathways (n = 7). Among the latter, the interval increased less than 30 ms during left BBB except in the patient with the high serum procainamide level, in whom the increase was 35 ms. Thus, the VA interval change that accompanied left BBB remained of localizing value with moderate blood levels of type I drugs, and an increase greater than or equal to 35 ms indicated a left free wall rather than posteroseptal pathway.

Adolescent↗
PubMed1983

Clinical pharmacology of the anticancer polypeptide neocarzinostatin.

The clinical pharmacology of the anticancer polypeptide neocarzinostatin was studied in 16 patients with disseminated neoplasia using a radioimmunoassay technique. Patients who received 2,400-3,600 U of the drug per square meter BSA by rapid IV infusion had triphasic plasma decay curves. For eight patients with normal hepatic and renal function, neocarzinostatin mean plasma half-lives were 0.14, 0.50, and 7.7 h. The mean plasma drug clearance was 32.4 ml/min/m2 and the apparent volume of distribution 19.3 l/m2. Two patients with liver dysfunction had shorter terminal plasma half-lives and greater drug clearance, while two with renal disease exhibited prolonged plasma half-lives and reduced drug clearances. The mean cumulative urinary excretion of neocarzinostatin was 69.1% of the administered dose at 72 h in three patients with normal hepatic and renal function. One patient with liver disease excreted 90.4%, while a patient with renal disease excreted only 58.1% of the dose in 24 h. In one patient with marked liver disease, biliary excretion accounted for 0.1% of the administered dose in 72 h. Cerebrospinal fluid concentrations of neocarzinostatin studied in two patients showed a CSF penetration of about 16% the plasma concentration at 1-5 h; concentrations persisted for 19 h in one patient with an Omayha reservoir. Neocarzinostatin was rapidly cleared from the plasma and eliminated in the urine. Dosage reductions of 50% are recommended for patients with impaired renal function, while no reduction or escalated doses could be tolerated by patients with liver disease. The pharmacologic data suggest a continuous IV infusion may be a more toxic but perhaps more effective schedule of administration.

Adult↗
PubMed1983

Effects of exercise and isoproterenol during atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

The effects of exercise and isoproterenol on atrial fibrillation (AF) were studied in 17 patients with Wolff-Parkinson-White syndrome (WPW) to assess the risk of developing a rapid ventricular response. Mean cycle length (R-R interval) and shortest R-R interval between both preexcited and nonpreexcited QRS complexes were recorded, as well as the percentage of preexcited complexes during control periods, during bicycle exercise, and during isoproterenol infusion. Exercise resulted in significantly shorter mean cycle length and the shortest R-R interval between nonpreexcited complexes. Exercise also resulted in a significantly lower percentage of preexcited complexes during AF, but had no effect on the R-R intervals between preexcited complexes. Isoproterenol had a variable effect on the percentage of preexcited QRS complexes, but resulted in significant shortening of mean cycle length and the shortest R-R interval between both normal and preexcited complexes. With isoproterenol, 12 of 17 patients had shortest preexcited R-R intervals less than or equal to 215 ms, compared with 6 of 17 in the control state. Isoproterenol infusion increased the rate of conduction over the accessory pathway during AF and allowed better assessment of the risk of excessively rapid rates occurring during AF. Exercise is not an adequate test for this purpose.

Atrial Fibrillation↗
PubMed1983

Bystander accessory pathway during AV node re-entrant tachycardia.

Between 1970 and July 1980, wide QRS tachycardia due to re-entry confined to the AV node with bystander involvement of an accessory atrioventricular pathway (AAV) was documented in three of 290 patients with the Wolff-Parkinson-White syndrome studied at Duke Medical Center. In each of the patients, at least one transition between wide and narrow QRS morphology was recorded without change in either the cycle length of tachycardia or the atrial activation sequence. Two of the three patients had a single left-sided AAV (lateral, postero-lateral) showing antegrade conduction only. The third patient had two right-sided AAVs (free wall, septal), each capable of bidirectional conduction. Initiation and termination of repetitive concealed conduction into the ventricular insert of an AAV appeared to be one mechanism determining bystander AAV participation. Documentation of the retrograde sequence of atrial activation during tachycardia, and examination of the effects of interpolated premature depolarizations from both the ventricle and mid-line atrium are the most helpful features in resolving the differential diagnosis of wide QRS tachycardia in patients with W-P-W syndrome.

Adolescent↗
PubMed1983

Basal and maximal inotropic state in renal hypertensive dogs with cardiac hypertrophy.

We studied three isovolumic indexes of contractility, i.e., dP/dtmax, dP/dtDP40, and (dP/dt)/TPmax, in normal dogs and in a matched group of chronically hypertensive dogs with left ventricular hypertrophy (LVH) [DP40, developed LV pressure of 40 mmHg; TP, total LV pressure above atmospheric]. The LVH was moderate in degree with the LV-to-body weight ratio 50% greater than in normal dogs. The experiments were performed under pentobarbital with open chest, autonomic blockade, and independent control of mean left atrial pressure (LAP) and mean aortic pressure (MAP). We found that dP/dtmax provided the most consistent comparison of inotropic state in the two groups under both basal conditions and with norepinephrine (NE). The other indexes occurred too early in systole to reflect complete LV activation, particularly during the infusion with NE. Under controlled conditions basal dP/dtmax of LVH dogs was 1.28 times the value of normal dogs, with the increase accounted for by the amplifier effect of the increase in LV mass. But with moderate lowering of aortic pressure, inotropic state was more easily compromised in LVH than in normal dogs. With steady-state stimulation by infusing increasing amounts of NE, dP/dtmax rose by 10 times basal in both LVH and normal dogs at maximum stimulation. The absolute value of the index was 1.31 times higher in the LVH group, with the amplifier effect thus the same as under basal conditions. The results suggest that basal and maximal inotropic states are normal in LVH under optimum loading conditions.

Animals↗
PubMed1983

Effects of energy delivery via a His bundle catheter during closed chest ablation of the atrioventricular conduction system.

In this paper we summarize our experience and report the characteristics of energy delivery in 23 patients who have undergone closed chest ablation of the normal atrioventricular (AV) conduction system for the treatment of refractory supraventricular arrhythmias. The induction of AV block was achieved by the synchronous delivery of electrical energy with a damped sinusoidal waveform utilizing a standard direct current defibrillator and a standard tripolar His bundle catheter. The procedure was well tolerated, though one patient experienced ventricular fibrillation, which was uneventfully converted with external paddles. Complete AV block was achieved in 20 of 23 patients and all were rendered arrhythmia free, though two still required antiarrhythmic drugs. A stable escape rhythm was seen in all patients with a cycle length of 1,294 +/- 243 ms. Creatine phosphokinase-MB was positive at low levels in 19 of 23 patients and cleared within 24 h. 99mTc pyrophosphate scans were faintly positive in only 2 of 22 patients. Left ventricular wall motion and ejection fractions were unchanged in 19 of 19 patients, two-dimensional echocardiography with microcavitation technique was unchanged in 12 of 12 patients, and a slight increase in pulmonary artery wedge pressure was seen in only 1 of 11 patients. Current, voltage, and their product (power) waveforms were recorded in 12 patients (12 recordings at a defibrillator setting of 200 J and 5 recordings at a defibrillator setting of 300 J) and revealed a complex voltage-current relationship due to changes occurring at the catheter electrode-tissue interface. At 200 J the peak values were 42.2 +/- 3.3 A, 2.16 +/- 0.11 kV, and 87.9 +/- 4.7 kW, while at 300 J the peak values were 58.2 +/- 2.8 A, 2.40 +/- 0.10 kV, and 134.4 +/- 6.7 kW, respectively. No instance of catheter disruption was seen, though "pitting" of the distal electrode (through which current passed) occurred in all but one catheter.

Adult↗
PubMed1982

Catheter technique for closed-chest ablation of the atrioventricular conduction system.

This report describes a catheter technique for ablating the His bundle and its application in nine patients with recurrent supraventricular tachycardia that was unresponsive to medical management. A tripolar electrode catheter was positioned in the region of the His bundle, and the electrode recording a large unipolar His-bundle potential was identified. In the first patient, two shocks of 25 and 50 J, respectively, were delivered by a standard cardioversion unit to the catheter electrode, resulting in an intra-His-bundle conduction defect. Subsequent delivery of 300 J resulted in complete heart block. In the next eight patients, an initial shock of 200 J was used. The His bundle was ablated by this single shock in six of these patients and by an additional shock of 300 J in one. In the remaining patient, conduction in the atrioventricular node was modified, resulting in alternating first and second-degree atrioventricular block. A stable escape rhythm was preserved in all patients. The procedure was well tolerated, without complications, and all patients have remained free of arrhythmia, without medication, for follow-up periods of two to six months.

Adult↗
PubMed1982

Bleomycin clinical pharmacology by radioimmunoassay.

Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m2 and the volume of distribution was 13.2 l/m2. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m2 and the volume of distribution was 19.2 l/m2. Bleomycin plasma clearance correlated well with serum creatinine (r2 = 0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

Adolescent↗
PubMed1982

Archival data in program evaluation and policy analysis.

Evaluators have typically avoided using existing data sets, choosing instead to collect their own information to maintain control over both the content and quality of the data. As demands on action researchers increase without provision for additional resources, primary data collection may become a luxury and the use of archival data may increase. Though archival data has practical and methodological advantages, there are limitations associated with the utilization of such information. The general problems with secondary data sources include the accuracy, acceptability and accessibility of the information. Following a discussion of these general problems, an example from the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS) reimbursement data set is presented to illustrate specific difficulties with using archival data for evaluation research. Strategies are then presented for minimizing these difficulties, including determining the feasibility of utilization of such data sources, methods for assessing their accuracy and factors to consider in the data acquisition process.

Archives↗
PubMed1981

Estimation of maximum left ventricular inotropic response from changes in isovolumic indices of contractility in the dog.

The effects of catecholamine infusion on three isovolumic indices of left ventricular (LV) contractility were studied under "steady-state" conditions in open-chest dogs with left atrial pressure held constant. The indices studied were (dP/dt)max; (dP/dt)DP40 where DP40 = developed LV pressure (LVP) of 5.3 kPa (40 mmHg) and dP/dt/TP)max, where TP = total LVP above atmospheric. There was a curvilinear relationship between dose of noradrenaline and the rise of each index, but the magnitude of the rise differed considerably. When heart rate was allowed to rise (dP/dt)max rose to about 800% of the basal value, whilst the other two indices both increased to about 300% of basal. The reason for the difference appeared to be related to the earlier timing of (dP/dt)DP40 and (dP/dt/TP)max. When heart rate was controlled (dP/dt)max increased to about 500% of basal, similar to findings reported by others in the maximum rate of isometric force development in isolated myocardium. During noradrenaline infusion (dP/dt)max always occurred before aortic valve opening and provided a satisfactory measure of inotropic change whilst the other indices apparently occurred too early in systole to reflect full ventricular "activation". However, during isoprenaline infusion blood pressure fell and estimates of inotropic reserve using (dP/dt)max were 40 to 100% in error due to early aortic valve opening until blood pressure was raised using methoxamine.

Animals↗
PubMed1981

16 Alpha-[125I]-beta-estradiol compared with [3H]-beta-estradiol as the tracer in estradiol receptor assays.

We assessed the potential usefulness of 16 alpha-[125I]-beta-estradiol in estradiol receptor assays as compared with a long-used [3H]-beta-estradiol dextran-coated charcoal method, measuring 472 consecutive human breast-cancer cytosols by both procedures. Six different preparations of 16 alpha-[125I]-beta-estradiol were used. Nonspecific binding in five batches was similar and comparable to [3H]-beta-estradiol. Although the sixth batch had increased nonspecific binding, this did not affect results. Dissociation constants were virtually identical (r = 0.94). Results were concordant for 98.5% of cytosols: 161 were negative and 304 positive by both methods and seven were positive by one method, negative by the other. Four were positive with the 125I procedure and undetectable with [3H]-beta-estradiol. Three were measurable by both methods, but were above the cut-off value in one and below it in the other. We find 16 alpha-[125I]-beta-estradiol to be an adequate substitute for [3H]-beta-estradiol in estradiol receptor assays.

Breast Neoplasms↗