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Biomedical subjects

D W Benson

Publications and source records attributed to D W Benson.

At least 91 records · Page 5Linked to original sources

Permanent cardiac pacing in patients with the long QT syndrome.

A permanent pacemaker was inserted in eight patients with the long QT syndrome. All had recurrent syncope or seizures, six had documented torsade de pointes and four had aborted sudden death. Among the eight patients, permanent pacing was instituted in three who were unsuccessfully treated with both a beta-adrenergic blocking agent and left cardiothoracic sympathectomy, and in two who proved refractory or intolerant to beta-blockers. Another three patients had pacemaker implantation and long-term beta-blocker therapy because of spontaneous atrioventricular (AV) block in one, aborted sudden death in one and patient preference in one. After pacing (70 to 85 beats/min), there was no significant change in the mean corrected QT interval, but the mean QT interval decreased significantly (534.4 +/- 51.4 to 425.6 +/- 18.9 ms, p less than 0.0001). Over a mean follow-up period of 35.1 +/- 18.9 months, all patients are alive and currently free of syncope. One patient without a history of stress-induced syncope had two syncopal episodes (believed to be due to hyperventilation) while under severe emotional stress, but has been symptom free for the past 5 years. One patient with an atrial demand (AAI) pacemaker developed dizziness due to documented episodes of AV block, but remains asymptomatic after conversion to atrial rate-responsive dual chamber (DDD) pacing. Either atrial or ventricular pacing combined with beta-blocker therapy appears to be effective treatment for a subset of patients with the long QT syndrome, by either preventing episodes of torsade de pointes or alleviating symptoms due to bradycardia from beta-blocker therapy.

Adolescent↗

Cardiac and skeletal muscle abnormalities in cardiomyopathy: comparison of patients with ventricular tachycardia or congestive heart failure.

Results of cardiac muscle and skeletal muscle biopsies were compared in 22 patients with cardiomyopathy; 11 patients presented with symptoms secondary to ventricular tachycardia (Group 1) and 11 had symptoms of severe congestive heart failure (Group 2). No patient had structural or ischemic cardiac disease. In Group 1 patients, hemodynamic abnormalities were subtle, but invasive study demonstrated dilated cardiomyopathy in two patients and restrictive cardiomyopathy in nine. In Group 2, eight patients had dilated cardiomyopathy and three had restrictive cardiomyopathy. Cardiac biopsy results were abnormal in all 22 patients and the abnormalities were similar for the two groups. Cardiac histologic study revealed a spectrum of abnormalities including fibrosis, dilated sarcoplasmic reticulum, increased numbers of intercalated discs and mitochondrial abnormalities. Histologic abnormalities of skeletal muscle were similar in each group, consisting of endomysial fibrosis and increased lipid deposits. Slightly more than half of the Group 1 and Group 2 patients also had a low concentration of skeletal muscle long chain acylcarnitine. These data demonstrate that abnormalities of both cardiac and skeletal muscle are common in patients with cardiomyopathy; abnormalities are similar whether initial symptoms are due to ventricular tachycardia or congestive heart failure. It is suggested that these patients with cardiomyopathy may have a generalized myopathy.

Adolescent↗

Single-chamber cardiac pacing with activity-initiated chronotropic response: evaluation by cardiopulmonary exercise testing.

In this study, sequential cardiopulmonary exercise testing was used to assess the physiologic benefits of a single-chamber ventricular pacing system that utilizes a piezoceramic sensor to adjust heart rate by detecting "physical activity." An initial exercise test was conducted with the pacemaker programmed (based on a randomization table) to either the fixed rate (VVI, 70 beats/min) or rate-variable (VVI-Act) mode, and the results were compared with those obtained during a second exercise test in which the pacemaker was programmed to the alternate pacing mode. A 1.5 to 2 hr rest period was permitted between exercise tests, each of which consisted of a symptom-limited constant speed (3.0 mph) Balke protocol with 2 min stages commencing at 0.0% grade with increments of 2.5% at end of each stage. Compared with findings during fixed-rate VVI pacing, VVI-Act pacing was associated with greater exercise-induced positive chronotropic response (mean maximum heart rate VVI-Act 128 +/- 15.3 beats/min vs VVI 90 +/- 28.4 beats/min; p less than .01), prolongation of exercise duration (VVI-Act 10.2 +/- 3.8 min vs VVI 7.7 +/- 2.5 min; p less than .01), increased peak oxygen consumption (VVI-Act 1617 +/- 656 ml O2/min vs VVI 1325 +/- 451 ml O2/min; p less than .01), and onset of anaerobic threshold at a higher oxygen consumption (VVI-Act 1208 +/- 343 ml O2/min vs VVI 1064 +/- 377 ml O2/min: p less than .01). Additionally, of 44 comparable exercise stages tested in the two pacing modes, perceived exertion (assessed by a numerical grading system) was lower in 38 of 44 instances during VVI-Act compared with VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Follow-up evaluation of infant paroxysmal atrial tachycardia: transesophageal study.

We report results of follow-up transesophageal electrophysiologic studies in 35 infants seven to 27 months old (mean, 12 months) in whom paroxysmal atrial tachycardia (PAT) using an accessory atrioventricular (AV) connection had been previously evaluated by transesophageal study in the first 2 months (mean, 14 days) of life. No infants were receiving antiarrhythmic drug therapy at the time of follow-up study. To evaluate AV conduction and initiate PAT, a standard transesophageal pacing protocol was used: single extrastimuli in sinus rhythm, incremental pacing to second-degree AV block, and burst pacing at cycle lengths near those resulting in second-degree AV block. If PAT was not initiated during the baseline period, the protocol was repeated during the infusion of isoproterenol and after administration of atropine. At follow-up study, PAT was reinitiated in 24 of 35 (68%) infants, six of whom had exhibited recent spontaneous recurrence of PAT. AV nodal function did not differ in those with and those without inducible PAT. However, when initial and follow-up studies were compared, changes in antegrade conduction of the accessory AV connection were observed, since only five of 10 infants with preexcitation at initial study continued to exhibit preexcitation at follow-up study (1/5 infants only after isoproterenol). Additionally, changes in retrograde conduction of the accessory AV connection were observed; the ventriculoatrial interval in PAT induced at follow-up study increased by 20 to 40 msec in eight of 24 infants and by 50 to 80 msec in five of 24 infants compared with the interval at initial study.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrioventricular Node↗

Effect of heart rate increase on dorsal aortic flow in the stage 24 chick embryo.

We evaluated the effect of increased heart rate on cardiac output and stroke volume in the stage 24 chick embryo (day 4 of a 21-day incubation). Blood flow was measured with a 20 MHz pulsed-Doppler flowmeter. Heart rate was increased by pacing with square wave stimuli (1 ms duration, less than 4 mA). The sinus venosus was paced from bipolar Teflon-coated silver electrodes in eight embryos and the ventricular apex was paced in three embryos. The pacing rates were at the intrinsic heart rate (P:I); 125% of intrinsic heart rate (P:125%I); and 150% of intrinsic heart rate (P:150%I). Physiologic measurements during pacing were compared to those obtained at the control intrinsic rate (I). We also evaluated the velocity profile of atrioventricular inflow and conotruncal outflow at intrinsic rate and during sinus venosus and ventricular pacing. With sinus venosus pacing, mean dorsal aortic blood flow was similar at control (1.07 +/- 0.05 mm3/s) and P:I (1.06 +/- 0.06 mm3/s) (mean +/- SEM). However, at P:125%I and P:150%I, mean dorsal aortic blood flow decreased significantly (P:125%I, 0.88 +/- 0.05 mm3/s; P:150%I, 0.67 +/- 0.07 mm3/s) (p less than 0.05). Stroke volume per beat also decreased with increasing heart rates (I, 0.41 +/- 0.02 mm3; P:I, 0.39 +/- 0.02 mm3; P:125%I, 0.28 +/- 0.02 mm3; P:150%I, 0.18 +/- 0.02 mm3) (p less than 0.05). With rapid sinus venosus pacing, the atrioventricular blood flow velocity profile showed a rate-dependent decrease in passive ventricular filling while active filling remained the same or increased slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modes of onset ("initiating events") for paroxysmal atrial tachycardia in infants and children.

Observations of spontaneous onset of paroxysmal atrial tachycardia (PAT) in infants and children have been infrequently reported. This study reports on modes of spontaneous onset of PAT in 22 infants and 8 children in whom onset of PAT was recorded during continuous electrocardiographic recording. During PAT, all 30 patients used the normal specialized atrioventricular conduction system for ventricular activation, with atrial activation occurring through an accessory atrioventricular connection (orthodromic reciprocating tachycardia). Wolff-Parkinson-White syndrome was present in 7 patients. Analysis of the mode of onset of PAT revealed that infants initiated PAT with atrial extrasystoles or sinus acceleration (a gradual shortening of the P-P interval). In 10 infants more than 10 PAT onsets were recorded, and in these infants the mode of onset was sinus acceleration. In 7 infants, both atrial extrasystole and sinus acceleration were observed to initiate PAT. In the older children, onset of PAT followed atrial extrasystole (3 patients), ventricular extrasystole (2 patients), and sinus pause with junctional escape (3 patients). It has been previously recognized that the natural history of these "initiating events" varies with patient age. Variations in frequency of spontaneous episodes of PAT may relate to chronologic variations in frequency and type of initiating events.

Adolescent↗

Transesophageal study of recurrent atrial tachycardia after atrial baffle procedures for complete transposition of the great arteries.

Transesophageal study was used for diagnosis and treatment of 51 episodes of tachycardia in 13 patients with complete transposition of the great arteries who had undergone atrial baffle procedure. At the time of atrial baffle procedure, patients were 6 to 36 months old (mean 23). Tachycardia (1 to 17 episodes per patient) first occurred 1 to 23 days (4 patients) or 1.8 to 12 years (9 patients) after atrial baffle. Transesophageal study was performed using a bipolar silicone rubber-coated catheter. Tachycardia conversion was accomplished with stimulation bursts using 4 to 10 stimuli 9.9 ms in duration at 20 to 28 mA and an interstimulus interval of 50 to 100 ms less than the atrial cycle length. All tachycardia episodes had regular atrial cycle lengths ranging from 200 to 350 ms. In 12 patients, second-degree atrioventricular (AV) block was observed during tachycardia, suggesting primary atrial tachycardia. However, in 1 patient, occurrence of AV block always resulted in tachycardia termination, suggesting the presence of AV reentrant tachycardia. Transesophageal stimulation converted 48 of 51 tachycardia episodes to sinus/junctional rhythm. Ten tachycardia episodes in 6 patients were transiently converted to atrial fibrillation lasting 3 seconds to 28 minutes before spontaneous conversion to sinus junctional rhythm. Conversion attempts were unsuccessful on 3 occasions. Acceleration of ventricular rate after stimulation necessitated DC cardioversion on 1 occasion. Conversion was not achieved in 2 tachycardia episodes using stimuli less than 10 mA. Transesophageal study is a safe and effective minimally invasive technique for diagnosis and treatment of tachycardia in infants and children who have had atrial baffle for transposition of the great arteries.

Child, Preschool↗

Subpopulations of human heart mitochondria.

Anatomically and biochemically distinct populations of cardiac mitochondria have been isolated from a number of animal species. The physiologic differences between subsarcolemmal (SS) and interfibrillar (IF) mitochondria, coupled with their different location within the cytomatrix, have led to speculation about possible specificities of function within the myocardial cell. To date, these two mitochondrial subpopulations have not been demonstrated in human cardiac tissue. Subsarcolemmal and interfibrillar cardiac mitochondria were isolated from papillary muscle removed from five patients undergoing mitral valve replacement surgery. Mitochondrial respiratory activity was determined polarographically. IF mitochondria had significantly higher state 3 (ADP-dependent) rates of respiration then SS mitochondria (116.7 +/- 7.1 versus 86.5 +/- 8.3 ng atoms or oxygen per minute per milligram mitochondrial protein; P less than 0.05 [mean +/- SE]). These data agree with similar studies performed in other animal species and support the concept of distinct subpopulations of mitochondria within the human myocardial cell.

Adenosine Diphosphate↗

Intracavitary electrode catheter cardioversion of atrial tachyarrhythmias in the dog.

This study examined factors determining efficacy of intracavitary cardioversion of atrial tachyarrhythmias in closed chest, anesthetized dogs with talc pericarditis. Electrode catheters were positioned transvenously with the cathode in the right atrial appendage. In Group 1 dogs (n = 6), three anode sites (superior and inferior venae cavae ostia and mid-right atrium) were tested with graded energy shocks to determine the lowest effective cardioversion energy at each anode position. In Group 2 dogs (n = 9), multiple cardioversion attempts with energy levels of 0.01 to 5.0 J were used to evaluate reproducibility of energy thresholds. In Group 3 dogs (n = 6) without talc-induced pericarditis, atrial pathologic study was done after five intracavitary shocks (0.5 or 5.0 J). In Group 1, cardioversion was achieved with 0.75 J or less with no significant difference in minimal effective cardioversion energies among the three anode positions tested. In Group 2, 98 (26%) of 372 cardioversion attempts were successful. Intra-animal minimal effective cardioversion energies varied widely, and timing of shocks relative to atrial electrograms did not influence efficacy. Complications were infrequent and included delayed sinus rhythm recovery, transient atrioventricular block and ventricular fibrillation. Ventricular fibrillation occurred in 9 (2.4%) of 372 shocks, and was associated with higher delivered energies (6 of 9 with greater than or equal to 1.0 J) and with shocks delivered 116 to 180 ms after onset of the QRS complex. In Group 3, two dogs had no histologic damage, three dogs had multiple small foci of subendocardial necrosis and in one dog these foci coalesced to involve half the atrial wall thickness. Thus, low energy cardioversion of atrial tachyarrhythmias is feasible using intracavitary electrodes. Synchronization of energy delivery to the QRS complex is important to minimize risk of ventricular fibrillation.

Animals↗

Electrophysiologic effects of flecainide acetate and its major metabolites in the canine heart.

Flecainide acetate, an investigational class 1 antiarrhythmic agent, undergoes biotransformation in man with production of 2 major metabolites: meta-O-dealkylated flecainide (S-24623) and the meta-O-dealkylated lactam of flecainide (S-26191). This study compared the effects of flecainide, S-24623 and S-26191 on cardiac electrophysiologic characteristics in the anesthetized dog. Each dog received 2 dose levels of 1 of the 3 test compounds after control measurements. Flecainide (2 and 4 mg/kg in 8 dogs), S-24623 (4 and 8 mg/kg in 8 dogs) and S-26191 (4 and 10 mg/kg in 7 dogs) were administered intravenously in dilute solution. Of the 3 compounds, only flecainide significantly prolonged sinus cycle length (p less than 0.01). However, both flecainide and S-24623 significantly prolonged minimum atrial paced cycle length with 1:1 atrioventricular conduction, atrioventricular nodal effective and functional refractory periods, and right ventricular effective refractory period. Metabolite S-26191 exhibited qualitatively similar but much weaker electrophysiologic actions. The maximal electrophysiologic effects of flecainide and S-24623 were approximately equivalent, but the metabolite was about one-half as potent on a milligram-permilligram basis, and lacked marked effects on infranodal (HV interval) conduction. S-26191 was less than one-tenth as potent as flecainide. Therefore, since both flecainide metabolites occur primarily in the conjugated form in plasma (i.e., free metabolite concentrations are low), it is unlikely that these compounds either potentiate flecainide's antiarrhythmic action or increase susceptibility to drug toxicity in the clinical setting.

Animals↗

Experimental myocardial ischemia. Differential injury of mitochondrial subpopulations.

Distinct populations of subsarcolemmal (SS) and inter-fibrillar (IF) rat cardiac mitochondria were studied following 15 and 30 minutes of warm and cold global ischemia. The respiratory control index, state 3, state 4, adenosine diphosphate-oxygen ratio, and specific enzyme activities of these mitochondrial populations were examined. The subsarcolemmar and IF mitochondria were both severely uncoupled and inhibited by warm ischemia. However, IF mitochondria had a higher RCI at each ischemic interval. In cold ischemia, IF mitochondria were not injured compared with control specimens. Subsarcolemmar mitochondria showed a trend towards a lower RCI that was statistically significant at 30 minutes with succinate as a substrate. These data implicate a differential injury of ischemia on the compartmentalized bioenergy metabolism of the myocardial cell.

Animals↗

Periodic procainamide for paroxysmal tachycardia.

We evaluated the efficacy of a single oral dose of procainamide to terminate paroxysmal tachycardia, when procainamide was taken shortly after onset of tachycardia, a regimen we have termed "periodic procainamide." In 12 patients (mean age 15 years) with non-life-threatening tachycardia (orthodromic reciprocating tachycardia, 8/12; ventricular tachycardia, 3/12; atrial flutter, 1/12) in whom intravenously administered procainamide (15 mg/kg at 1 mg/kg/min) terminated tachycardia, efficacy of a single oral dose of procainamide (25 mg/kg) to terminate tachycardia was tested during electrophysiologic study. After oral administration of procainamide, tachycardia was terminated and could not be reinitiated in 11 of 12 patients (9/12 less than 75 min, 2/12 greater than 120 min after administration). Time of tachycardia termination approximately coincided with the time of peak serum concentration of procainamide after the single oral dose. Delayed response or failure of procainamide to terminate tachycardia was associated with delayed and diminished peak serum procainamide concentration. After evaluation, 10 responders were instructed to take a single dose of procainamide when tachycardia occurred. During a mean follow-up of 9 months (range 2 to 17) seven of 10 patients had an opportunity to use periodic procainamide on one to more than 100 occasions; four of 10 patients have not had recurrence of tachycardia. Tachycardia was successfully terminated in six of seven patients using the periodic regimen and could not be terminated on the first out-of-hospital use in one of seven patients. Success of periodic procainamide was predicted during evaluation by rapid termination of tachycardia after oral administration.

Administration, Oral↗

Prediction of digoxin treatment failure in infants with supraventricular tachycardia: role of transesophageal pacing.

Transesophageal atrial pacing was used to initiate and terminate tachycardia in 24 infants (seven female and 17 male, aged 1 to 34 days) with ECG documentation of supraventricular tachycardia. Six infants received no chronic treatment, and chronic oral digoxin prophylaxis was administered to 18 infants in an effort to prevent recurrences of tachycardia. In these 18 infants, the effectiveness of digoxin therapy in preventing the initiation of tachycardia by transesophageal pacing was compared with its ability to prevent spontaneous recurrences of supraventricular tachycardia. While receiving chronic oral digoxin therapy, tachycardia could be reinitiated in 15/18 (83%) infants. In these infants, the cycle length of tachycardia and the atrioventricular interval were the same before and during chronic digoxin treatment. Three infants in whom tachycardia could not be initiated during chronic digoxin therapy had no spontaneous recurrences during 6 months of follow-up, whereas 10/15 (67%) infants in whom tachycardia could be reinitiated had clinically significant recurrences in spite of chronic digoxin therapy. Six infants who received no chronic drug treatment had no documented recurrences during 6 months of follow-up. This study demonstrates that digoxin was effective in preventing significant spontaneous recurrences of supraventricular tachycardia in only 8/18 (44%) infants treated with digoxin. The ability to initiate supraventricular tachycardia with transesophageal pacing may be useful in determining which digoxin-treated infants are at risk for recurrence. Finally, not all infants with supraventricular tachycardia require chronic prophylaxis; six of the untreated infants had no documented recurrences.

Atrioventricular Node↗

Cardiovascular collapse in infants: association with paroxysmal atrial tachycardia.

Four infants, aged 16 to 28 days (mean 23 days), were seen in the emergency room with acute cardiovascular collapse and with normal heart rate and rhythm. During evaluation for cardiovascular collapse, no infant had sepsis; cardiac assessment revealed normal intracardiac anatomy but global cardiac chamber enlargement and poor left ventricular systolic function, which resolved with supportive treatment. However, three of the four infants demonstrated ventricular preexcitation on their surface electrocardiogram and, subsequently, two infants had transient episodes of tachycardia. During a transesophageal pacing study to evaluate inducibility and electrophysiologic characteristics of tachycardia, sustained tachycardia was initiated in all four infants. Reentrant tachycardia used an accessory atrioventricular connection as evidenced by the presence of preexcitation during sinus rhythm (three infants), the ability to initiate and terminate tachycardia by programmed electrical stimulation (four infants), minimum ventriculoatrial interval recorded in the esophagus (V-Aeso) exceeded 70 ms (four infants), transient bundle branch block during tachycardia prolonged the cycle length and the V-Aeso by 30 to 50 ms (three infants). Findings in these infants suggested prior episodes of prolonged tachycardia as the probable etiology of the cardiovascular collapse.

Ampicillin↗

Subpopulations of skeletal muscle mitochondria: response to ischemia.

The respiratory activity of distinct populations of subsarcolemmal (SS) and interfibrillar (IF) skeletal muscle mitochondria was studied in rat hindlimb muscle subjected to 30 min of global ischemia at 37 C. State 3 (ADP-dependent) and state 4 (ADP-independent) rates of respiration were determined polarographically using glutamate as the substrate, in order to calculate the respiratory control index (RCI). The RCI is the ratio of state 3 to state 4 respirations and is a sensitive indicator of mitochondrial coupling. An approximately 20 per cent decline in RCI was noted in the SS mitochondria following 30 min of warm ischemia. This decrease was a direct result of a significant decline in the state 3 respiratory rates. IF RCIs following the ischemic interval were not different from control. These data support the concept of separate populations of mitochondria within the skeletal muscle cell and demonstrate a specific injury pattern in the response to ischemia.

Animals↗