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Biomedical subjects

T W Simmons

Publications and source records attributed to T W Simmons.

At least 19 recordsLinked to original sources
PubMed1995

Radiofrequency catheter ablation for management of symptomatic ventricular ectopic activity.

OBJECTIVES: This study assessed the useful role of intracardiac mapping and radiofrequency catheter ablation in eliminating drug-refractory monomorphic ventricular ectopic beats in severely symptomatic patients. BACKGROUND: Ventricular ectopic activity is commonly encountered in clinical practice. Usually, it is not associated with life-threatening consequences in the absence of significant structural heart disease. However, frequent ventricular ectopic beats can be extremely symptomatic and even incapacitating in some patients. Currently, reassurance and pharmacologic therapy are the mainstays of treatment. There has been little information on the use of catheter ablation in such patients. METHODS: Ten patients with frequent and severely symptomatic monomorphic ventricular ectopic beats were selected from three tertiary care centers. The mean frequency +/- SD of ventricular ectopic activity was 1,065 +/- 631 beats/h (range 280 to 2,094) as documented by baseline 24-h ambulatory electrocardiographic (ECG) monitoring. No other spontaneous arrhythmias were documented. These patients had previously been unable to tolerate or had been unsuccessfully treated with a mean of 5 +/- 3 antiarrhythmic drugs. The site of origin of ventricular ectopic activity was accurately mapped by using earliest endocardial activation time during ectopic activity or pace mapping, or both. RESULTS: During electrophysiologic study, no patient had inducible ventricular tachycardia. The ectopic focus was located in the right ventricular outflow tract in nine patients and in the left ventricular posteroseptal region in one patient. Frequent ventricular ectopic beats were successfully eliminated by catheter-delivered radiofrequency energy in all 10 patients. The mean number of radiofrequency applications was 2.6 +/- 1.3 (range 1 to 5). No complications were encountered. During a mean follow-up period of 10 +/- 4 months, no patient had a recurrence of symptomatic ectopic activity, and 24-h ambulatory ECG monitoring showed that the frequency of ventricular ectopic activity was 0 beat/h in seven patients, 1 beat/h in two patients and 2 beats/h in one patient. CONCLUSIONS: Radiofrequency catheter ablation can be successfully used to eliminate monomorphic ventricular ectopic activity. It may therefore be a reasonable alternative for the treatment of severely symptomatic, drug-resistant monomorphic ventricular ectopic activity in patients without significant structural heart disease.

Anti-Arrhythmia Agents↗
PubMed1994

A volume-activated taurine channel in skate hepatocytes: membrane polarity and role of intracellular ATP.

Osmoregulation in isolated hepatocytes and perfused livers of the little skate (Raja erinacea), an osmoconforming marine elasmobranch, is mediated in part by the uptake or release of the intracellular osmolyte taurine. To further characterize the efflux mechanism, [14C]taurine release and Na(+)-independent uptake were assessed after cell swelling in hypotonic media containing 0.1-100 mM taurine. Rate coefficients for [14C]taurine uptake (0.016 +/- 0.002 min-1) and efflux (0.015 +/- 0.003 min-1) were similar and independent of extracellular taurine concentration, indicating that a taurine-permeable channel mediates the release of this amino acid after cell swelling. Volume-activated taurine uptake and efflux were both blocked by pretreatment with the metabolic inhibitors 2,4-dinitrophenol, antimycin A, and KCN plus iodoacetate, by the sulfhydryl-reactive compound N-ethylmaleimide and the transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. [14C]taurine release via this channel was immediately blocked if isotonicity was restored or a membrane-permeable metabolic inhibitor (0.5 mM 2,4-dinitrophenol) was added at different times after a hypotonic stimulus. Similar, although delayed, effects were noted with antimycin A and KCN plus iodoacetate. When isolated perfused skate livers were exposed to hypotonic stimuli, all of the taurine was released into the sinusoidal circulation, but not into bile, an effect that was also blocked by restoring isotonicity. These findings demonstrate that taurine efflux from skate hepatocytes after cell swelling is mediated by a channel. This channel is localized to the basolateral membrane and appears to require the continual presence of intracellular ATP for its function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Catheter ablation of the atrioventricular junction using radiofrequency energy and a bilateral cardiac approach.

Radiofrequency current catheter ablation was used successfully to create complete atrioventricular (AV) block in 60 of 61 patients (98%) with drug refractory supraventricular tachyarrhythmias. The remaining patient developed Mobitz I AV block and is clinically improved (clinical efficacy 100%). In 54 patients (89%), complete AV block was achieved using a right-sided approach. Patients aged > 60 years needed significantly fewer right-sided radiofrequency applications to produce complete AV block (5.3 +/- 5.3 vs 11.1 +/- 10.0; p = 0.009). In 6 of 7 patients with unsuccessful right-sided ablation, a left ventricular approach was used. In each case, 1 to 4 additional radiofrequency applications produced complete AV block. Patients with unsuccessful right-sided ablation were generally younger than those with successful ablation (50 +/- 16 vs 64 +/- 11; p = 0.007). It is concluded that catheter ablation using radiofrequency current is an extremely effective means of producing complete AV block. Older patients appear to be more susceptible to right-sided radiofrequency approaches. Left ventricular ablation easily produces complete AV block in patients refractory to right-sided attempts.

Adult↗
PubMed1992

Flecainide therapy in patients treated for supraventricular tachycardia with near normal left ventricular function.

Concerns about the safety and efficacy of class IC antiarrhythmic agents have arisen as a result of the recent CAST data. We reviewed records of 175 consecutive patients treated with flecainide between July 1, 1988 and July 5, 1989. One hundred ten patients with normal or mildly impaired left ventricular function and symptomatic supraventricular arrhythmias were identified. Follow-up data were obtained on 102 patients for a mean of 14 months. The average duration of flecainide therapy was 13 months. Tachyarrhythmias treated included atrial fibrillation/flutter, atrioventricular reentry, and atrioventricular nodal reentry. Flecainide provided effective antiarrhythmic therapy in 62% of the patients and was discontinued in 38% of the patients. Left atrial size did not predict treatment failure. Two patients developed proarrhythmic events (nonsustained ventricular tachycardia). There were no deaths during the follow-up period. In conclusion, flecainide provides safe and effective therapy for supraventricular tachyarrhythmias in patients with normal or mildly impaired left ventricular function.

Atrial Fibrillation↗
PubMed1992

Analysis of deaths in patients with an implantable cardioverter defibrillator.

The cause of death and clinical characteristics of 26 patients that died after implantable cardioverter defibrillator placement were reviewed and compared to the 145 patients still living after a mean follow-up of 17 months. Operative mortality was 4% (7/171) and resulted from postoperative ventricular arrhythmias (four patients), heart failure (two patients), and respiratory failure (one patient). Operative mortality was significantly higher (1.7% vs 9.6%, P less than 0.05) following concomitant surgical procedures. Total late mortality was 11% (18/171). Thirteen deaths (75%) occurred in-hospital from progressive deterioration of left ventricular function (nine patients), arrhythmia (two patients), and noncardiac causes (two patients). Outpatient mortality was 3.5% (6/171) and resulted from presumed sudden cardiac death in five of six patients; two of the five had devices that were inactive, one had high defibrillation thresholds, and two had suspected bradyarrhythmic deaths. One postoperative death and one late in-hospital death were also considered sudden cardiac deaths for a total of seven patients with defibrillation system failures. By multivariant analysis, preoperative clinical characteristics associated with a worse prognosis following defibrillator implantation were identified: presentation as ventricular tachycardia (P less than 0.02), induction of sustained monomorphic ventricular tachycardia (P less than 0.05), poor left ventricular performance (P less than 0.01), poor functional status (P less than 0.001), and the use of diuretics (P less than 0.01). Frequent device discharges (P less than 0.001) and concomitant antitachycardia pacing systems (P less than 0.001) were markers for greater arrhythmia recurrence and were potent predictors of a worse prognosis and particularly sudden death.

Arrhythmias, Cardiac↗
PubMed1992

L-cysteine and S-(1,2-dichlorovinyl)-L-cysteine transport in rat liver canalicular membrane vesicles: potential reabsorption mechanisms for biliary metabolites of glutathione and its S-conjugates.

Transport of L-cysteine and a cysteine S-conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC) was investigated in rat liver canalicular plasma membrane (cLPM) vesicles. Cysteine uptake into an osmotically active intravesicular space was temperature sensitive and further enhanced by an inwardly directed Na+ gradient. Na(+)-dependent and -independent L-cysteine uptake exhibited saturation kinetics with apparent Km of 53 +/- 0.7 and 1300 +/- 300 microM and Vmax of 95 +/- 21 and 1600 +/- 200 pmol.mg protein-1.10 sec-1 for the Na(+)-dependent components, and an apparent Km of 207 +/- 48 microM and a Vmax of 355 +/- 71 pmol.mg protein-1.10 sec-1 for the Na(+)-independent component. Na(+)-dependent uptake was inhibited by L-alanine, glycine, L-phenylalanine and L-leucine, whereas Na(+)-independent uptake was inhibited by L-phenylalanine, L-leucine and 2-amino-2-norbornanecarboxylic acid. Both Na(+)-dependent and -independent L-cysteine transport processes were inhibited by several cysteine S-conjugates, with DCVC having the strongest effect. Inhibition of [35S]L-cysteine uptake by DCVC was noncompetitive with a Ki of 1.2 +/- 0.1 mM. On the other hand, uptake of [35S]DCVC by the rat cLPM vesicles was not stimulated by a Na(+)-gradient, but was inhibited by several other amino acids, including L-cysteine. Further investigation of [35S]DCVC uptake in rat cLPM vesicles indicated a saturable Na(+)-independent process with an apparent Km of 155 +/- 42 microM, and a Vmax of 393 +/- 53 pmol.mg protein-1.5 sec-1.2+.

Absorption↗
PubMed1991

Intrahepatic conversion of a glutathione conjugate to its mercapturic acid. Metabolism of 1-chloro-2,4-dinitrobenzene in isolated perfused rat and guinea pig livers.

Because of the low hepatic activity of gamma-glutamyl-transferase in the rat, the liver is generally considered to play only a minor role in the degradation of glutathione conjugates, a limiting step in mercapturic acid formation. Recent findings indicate, however, that the liver has a prominent role in glutathione catabolism, particularly in species other than rat. To examine the contributions of liver to mercapturic acid biosynthesis, mercapturate formation was compared in isolated perfused livers from rats and guinea pigs dosed with either 0.3 or 3.0 mumol of 1-chloro-2,4-dinitrobenzene (CDNB). Chemically synthesized glutathione conjugate, mercapturic acid, and intermediary metabolites of CDNB were used as standards in the high performance liquid chromatography analysis of bile and perfusate samples. Biliary excretion accounted for almost all of the recovered metabolites. A marked species difference was observed in the pattern of CDNB metabolism. Rat livers dosed with 0.3 mumol of CDNB excreted 55% of total biliary metabolites as the glutathione conjugate and 8.2% as the mercapturic acid, whereas guinea pig livers excreted only 4.8% as the glutathione conjugate and 47% as the mercapturate. Mercapturic formation was also dose-dependent, with a larger fraction formed at the 0.3- versus the 3.0-mumol dose (8.2 versus 3.7% in the rat; 47 versus 19% in the guinea pig). Hepatic conversion of the glutathione conjugate to the mercapturic acid was markedly inhibited in both species after retrograde intrabiliary infusion of acivicin, an inhibitor of gamma-glutamyltransferase activity. These findings provide direct evidence for intrahepatic biosynthesis of mercapturic acids. Thus, glutathione conjugates synthesized within hepatocytes are secreted into bile and broken down to cysteine conjugates; the latter are then presumably reabsorbed by the liver, N-acetylated to form the mercapturic acid and re-excreted into bile.

Acetylcysteine↗
PubMed1991

Polarity of hepatic glutathione and glutathione S-conjugate efflux, and intraorgan mercapturic acid formation in the skate.

Mechanisms of hepatic glutathione and glutathione S-conjugate efflux were investigated in isolated hepatocytes and perfused liver of the little skate (Raja erinacea). Glutathione was released by isolated skate hepatocytes at a rate of 0.12 +/- 0.03 nmol.hr-1.(mg protein)-1. In the perfused liver, glutathione concentrations in bile were high (approximately 0.7 mM) compared to hepatic tissue levels (0.61 +/- 0.11 mumol.g-1). During the first hour of perfusion, the biliary glutathione excretion rate was 3 nmol.hr-1.(g liver)-1, whereas glutathione accumulated in the recirculating perfusate at a rate of only 1.5 nmol.hr-1.(g liver)-1. Release of glutathione by isolated hepatocytes and perfused liver was not affected by the addition of acivicin, an inhibitor of gamma-glutamyltransferase (EC 2.3.2.2), to cell suspension medium or liver perfusate. 1-Chloro-2,4-dinitrobenzene (CDNB) was taken up by isolated hepatocytes, conjugated to glutathione, and released as S-(2,4-dinitrophenyl) (DNP)-glutathione. After infusion of 0.5 mumol CDNB in perfused liver, S-DNP-glutathione was concentrated in bile (0.5 mM) and was associated with choleresis. S-DNP-Conjugates of cysteinylglycine, cysteine and N-acetylcysteine, were also found in bile, suggesting intrahepatic breakdown of S-DNP-glutathione and subsequent acetylation of the resulting cysteine conjugate to form the mercapturic acid, S-DNP-N-acetylcysteine. This mercapturic acid accounted for 31% of the total S-DNP-conjugates collected in bile. In contrast, neither S-DNP-glutathione nor other S-DNP-conjugates were detected in the perfusate (less than 0.5 microM). These findings demonstrate that biliary excretion is the predominant route for efflux of glutathione and a glutathione S-conjugate from skate liver. The results also identify an intrahepatic pathway for mercapturic acid biosynthesis facilitated by biliary glutathione S-conjugate excretion.

Acetylcysteine↗
PubMed1991

Patients with a high defibrillation threshold: clinical characteristics, management, and outcome.

Of 125 patients prepared to receive implantable cardioverter-defibrillators (ICDs) with the patch-patch configuration of the difibrillating electrodes, 23 (18%) had high (greater than or equal to 25 joules) defibrillation thresholds (DFTs). These patients had lower left ventricular ejection fractions (27 +/- 12 vs 34 +/- 13; p less than 0.03) and a higher incidence of previous heart surgery (47% vs 19%; p less than 0.01) than patients with normal DFTs but did not differ in age, type of heart disease, incidence of concomitant heart surgery, or use of antiarrhythmic medication. Defibrillators were implanted in 18 of these 23 patients, 12 during the initial surgery and six after repeat DFT testing 2 weeks later. After 22 +/- 11 months of follow-up, four patients with ICDs died (two suddenly, and two of nonsudden cardiac causes). Two patients without ICDs died of nonsudden cardiac causes. Appropriate shocks were received by five patients (29%) including both who died suddenly later. A high DFT may be more common than previously stated. It is associated with poor ventricular function and previous heart surgery. Repeated DFT testing may be useful in some patients. A high DFT does not preclude successful ICD shocks, but other therapies may provide better results.

Aged↗
PubMed1991

DDIR versus VVIR pacing in patients with paroxysmal atrial tachyarrhythmias.

Patients with sinus node dysfunction (SND) in particular those with tachycardia-bradycardia syndrome and patients undergoing atrioventricular nodal ablation procedures for refractory paroxysmal atrial tachyarrhythmias (PAT), are candidates for single chamber (VVIR mode) or dual chamber rate responsive (DDIR mode) systems. To evaluate the benefits and disadvantages of each pacing mode we retrospectively analyzed 33 patients with a history of frequent PAT who received a VVIR (22 patients); or a DDDR pacemaker (11 patients) programmed to the DDIR mode. The mean follow-up time was 25 and 18 months, respectively. Preimplant left atrial diameter was significantly smaller in the DDIR group. Chronic atrial fibrillation developed in 54% of the VVIR patients and 27% of the DDIR group, but this difference was not significant. Complications of patients with VVIR pacemakers included new mitral and tricuspid insufficiency, stroke, pacemaker intolerance and aggravated congestive heart failure. Patients with DDIR pacemakers had a lower incidence of symptoms and complications. However, this group received more antiarrhythmic medication, required a closer follow-up, and their pacemakers needed frequent reprogramming. Our findings suggest that VVIR is a poor choice for patients with SND, congestive heart failure, and PAT, and that DDIR may be an acceptable alternative.

Anti-Arrhythmia Agents↗
PubMed1991

Early clinical experience with a minute ventilation sensor DDDR pacemaker.

UNLABELLED: The new DDDR pacemaker META DDDR utilizes a minute ventilation sensor based on transthoracic impedance measurements. The sensor determines the metabolic indicated interval, the atrioventricular (AV) delay and the postventricular atrial refractory period (PVARP). The baseline PVARP must be carefully selected to define nonphysiological tachycardias. If a P wave falls within the PVARP the pacemaker will automatically switch to the VVIR mode. This behavior prevents tracking of paroxysmal atrial tachyarrhythmias (PAT). Twenty-eight patients with sinus node dysfunction (n = 20), AV junction ablation (n = 5), complete or intermittent AV block (n = 3); who received a META DDDR pacemaker were studied. The mean age was 65 +/- 13 years. RESULTS: mode switching (reversion) to VVIR was observed in 57% of the patients. Forty-two percent had episodes of mode switching to VVIR during a stress test, four related to PAT, and seven to sinus tachycardia. Fifty percent had episodes of mode switching to VVIR during a 24-hour Holter, four related to PAT, three to retrograde P wave sensing, and two to sinus tachycardia. At the last follow-up, 20 of the 26 patients initially programmed to the DDDR mode remained in the DDDR mode, while five were reprogrammed to the DDD and one to the VVIR mode. Mode switching has a high sensitivity but a low specificity for PAT. It appears to be a useful approach to prevent rapid tracking of atrial tachyarrhythmias. Careful PVARP programming is critical to appropriate reversion behavior, but further modifications of the algorithm are needed to improve its performance.

Aged↗
PubMed1991

Implantable cardioverter defibrillator implanted by nonthoracotomy approach: initial clinical experience with the redesigned transvenous lead system.

Standard implantation procedure for the implantable cardioverter defibrillator (ICD) has traditionally required a thoracotomy approach. A newly revised nonthoracotomy defibrillator lead system that uses a single transvenous tripolar endocardial lead alone or in combination with a subcutaneous/submuscular patch lead was introduced into clinical trials in September, 1990. Fourteen patients requiring a cardioverter defibrillator for recurrent sustained ventricular tachycardia (eight patients) or aborted sudden cardiac death (six patients) were evaluated for implantation of this lead system. Primary successful lead system implantation was obtained in nine patients. The remaining five patients had unacceptably high defibrillation thresholds (DFTs) for implantation. One of the nine initially successful implants demonstrated unacceptable DFTs and cross-talk inhibition from a permanent pacemaker necessitating removal of the nonthoracotomy lead system and replacement with a conventional lead system via thoracotomy. All remaining primary implanted patients experienced successful conversion of induced ventricular fibrillation prior to hospital discharge. Continued follow-up and greater experience to confirm the durability and efficacy of the nonthoracotomy AICD lead system are needed.

Aged↗
PubMed1990

Modulation of Na+/alanine cotransport in liver sinusoidal membrane vesicles by internal divalent cations.

Rat liver basolateral plasma membrane (blLPM) vesicles resuspended in 5 mM Mg2(+)-, Ca2(+)-, Mn2(+)- or Co2(+)-containing media exhibited a markedly lower rate of Na(+)-stimulated L-alanine transport. Divalent cation inhibition of L-alanine uptake was dose dependent, and was observed only when the vesicles were pre-loaded with the divalent cations. The presence or absence of the metal ions in the extravesicular incubation media had no effect on L-alanine transport. Conversely, pretreatment of the vesicles with 0.2 mM of either EGTA or EDTA resulted in higher initial rates of L-alanine transport. This stimulation was overcome by addition of excess divalent cation to the vesicle suspension solution. Since these blLPM vesicles are primarily oriented right-side-out, the divalent cation inhibition of L-alanine transport appears to be a result of their interaction with cytosolic components of the cell membrane. Total Na+ flux as measured with 22Na+ was not affected by intravesicular 5 mM Mg2+ or Ca2+, indicating that the inhibition was not due to dissipation of the Na+ gradient. These observations suggest that intracellular divalent cations may serve to modulate L-alanine transport across the liver cell plasma membrane.

Alanine↗
PubMed1990

Pacemaker and defibrillator combination therapy for recurrent ventricular tachycardia.

The judicious use of antitachycardia pacemakers can enhance the benefits of automatic implantable cardioverter defibrillators in certain patients. Both devices were implanted in 10 highly selected patients with drug-refractory pace-terminable sustained ventricular tachycardia. During the observation period of 8 +/- 4.8 months, the automatic pacemakers detected 1,542 episodes of ventricular tachycardia and appropriately managed 1,373. The automatic implantable defibrillator was activated at least once in every patient; on two documented occasions, the defibrillator discharged because the automatic pacemaker accelerated the tachycardia. Concomitant antiarrhythmic drugs could be reduced but not withdrawn. With meticulous device programming and testing, the two systems in combination can work synergistically to manage malignant ventricular arrhythmias in carefully selected patients.

Aged↗
PubMed1989

Selenium modulates peroxidation in the absence of glutathione peroxidase in Musca domestica.

Adult houseflies fed a low-selenium diet showed a 73% decrease in total Se compared to those given 1.0 ppm Se in their drinking water. This decrease was associated with a 84.4% increase in thiobarbituric acid reactants and a 16.3% increase in conjugated dienes. These increases were unrelated to activities of glutathione S-transferases, superoxide dismutases and catalase and to levels of reduced and oxidized glutathione, all of which were unaltered by Se deficiency. Since houseflies lack glutathione peroxidase, Se apparently modulates peroxidation in these animals independent of the antioxidant enzymes and glutathione.

Animals↗
PubMed1989

Selenium-independent glutathione peroxidase activity associated with glutathione S-transferase from the housefly, Musca domestica.

1. A glutathione S-transferase having Se-independent glutathione peroxidase activity was isolated from 100,000 g supernatant from housefly homogenate. 2. The specific activity of the partially purified Se-independent glutathione peroxidase was 1776 nmol NADPH oxidized/min/mg protein, representing an 87-fold purification. 3. The Mr of this enzyme was estimated to be 37,000 and 26,000 by gel filtration chromatography and gel electrophoresis, respectively. 4. Selenium-dependent glutathione peroxidase activity could not be detected in this same supernatant. 5. Se-independent glutathione peroxidase activity should be considered in future studies of the insect antioxidant defense system.

Animals↗
PubMed1989

Relative importance of intracellular glutathione peroxidase and catalase in vivo for prevention of peroxidation to the heart.

The relative importance in vivo of catalase and the selenoenzyme glutathione peroxidase for protection against peroxidation was assessed in the rat heart. Each of these enzymes was modulated by feeding animals a low selenium diet either unsupplemented or supplemented with 0.5 parts per million of selenium, with or without the catalase inhibitor, 3-amino-1,2,4-triazole, in their drinking water. After 8 weeks, selenium deficient rats had 88% reductions in cytosolic and mitochondrial glutathione peroxidase activities. These reductions were accompanied by increased peroxidation in heart homogenates and mitochondrial suspensions. Since increased mitochondrial peroxidation only occurred when both the cytosolic and mitochondrial glutathione peroxidase activities were compromised, these selenoenzymes appear to work in tandem and reductions in both are a prerequisite for increased peroxidation in this organ. Peroxidation did not occur in aminotriazole treated animals even though cytosolic catalase activity was inhibited by 65-80%. Moreover, inhibition of catalase activity did not exacerbate the level of peroxidation in selenium deficient animals depleted of glutathione peroxidase activity. Because increased peroxidation was only associated with reductions in glutathione peroxidase activity irrespective of catalase activity, the selenoenzyme appears to be more important for detoxification of hydrogen peroxide in the heart.

Amitrole↗