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Biomedical subjects

T W Simmons

Publications and source records attributed to T W Simmons.

36 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The use of beep-o-grams in the assessment of automatic implantable cardioverter defibrillator sensing function.

Noninvasive assessment of sensing performance in the automatic implantable cardioverter defibrillator is limited by the absence of telemetry or memory functions. The adaptation of the electrophysiological test mode into a "beep-o-gram" recording, with simultaneous audible tones and a surface electrocardiogram, was used in the confirmation of sensing malfunction. Eleven of 13 recordings in patients with documented or clinically suspected inappropriate defibrillator discharges (group 1) demonstrated evidence of definite oversensing. Nonspecific oversensing or undersensing was present in 77% of 27 randomly selected asymptomatic patients without known sensing malfunction (group 2). The sensitivity and specificity for identifying definite oversensing was 85% and 60%, respectively. The beep-o-gram system is a reliable, noninvasive means of confirming sensing malfunction in the automatic implantable cardioverter defibrillator. Its specificity is limited by the detection of subclinical sensing aberrations, to some degree related to the device's automatic gain control sensing algorithm.

Electric Countershock↗

Significance of alterations in hepatic antioxidant enzymes. Primacy of glutathione peroxidase.

The relative contributions of catalase and the selenoenzyme glutathione peroxidase (GSH-Px) were elucidated in the rat liver by selectively modulating the activities of these enzymes using dietary selenium (Se) and the catalase inhibitor 3-amino-1,2,4-triazole (3-AT). Increased peroxidation occurred only in Se-deficient rats with markedly reduced cytosolic and mitochondrial GSH-Px activities. Although 3-AT treatment resulted in a 75% reduction of hepatic catalase activity and also a 20% reduction of both cytosolic and mitochondrial superoxide dismutase (SOD) activity, no incremental increase in peroxidation was observed over that associated with Se deficiency. In Se-deficient animals, treatment with 3-AT resulted in a doubling of cytosolic GSH-Px. This was associated with a 49% elevation in hepatic Se suggesting that increased Se may have contributed to the enhanced GSH-Px activity. These results suggest that GSH-Px plays the pivotal role in preventing hepatic peroxidation. Furthermore, the effects of 3-AT in vivo are not restricted to inhibition of catalase activity insofar as it also affects cytosolic GSH-Px activity and cytosolic and mitochondrial SOD activities.

Amitrole↗

The effect of selenium deficiency on peroxidative injury in the house fly, Musca domestica. A role for glutathione peroxidase.

Selenium-dependent glutathione peroxidase activity is documented for the first time in insects. Reduction in glutathione peroxidase activity in the cytosol of adult house flies by lowering selenium in the diet results in significant increases in peroxidative injury. Catalase activity, while higher in low-selenium flies than in selenium-supplemented flies, does not prevent lipid peroxidation. The discovery of glutathione peroxidase activity in insects eliminates an anomaly which partially limited the usefulness of these animals as models for the study of the antioxidant defense system.

Animals↗

Effect of ischaemia on overdrive suppression in isolated, blood-perfused atrial preparations of dogs.

The magnitude of overdrive suppression of the SA nodal pacemaker activity was markedly influenced by its ischaemia which was produced by occlusion of the perfusion tubing close to the sinus node artery in the in-situ and isolated canine sino-atrial node preparations. In all isolated preparations, postdrive suppression was significantly augmented after occlusion of the perfusion system for at least 120 seconds. It is concluded that total ischaemia depresses sino-atrial node function in the atropinized canine heart and that postdrive suppression is a good index of such impaired function.

Animals↗

Effects of temperature on norepinephrine-induced sinus acceleration and overdrive suppression in the isolated dog atrium.

Using an isolated, blood-perfused atrium preparation, the effects of temperature on SA nodal pacemaker activity were investigated in 9 preparations. The PP interval decreased as temperature was raised. Regular sinus rhythm and atrial contraction were maintained above approximately 26 degrees C. Below 26 degrees C, sinus depolarization still showed a regular rate, although atrial contractions had ceased. At about 24 degrees C, atrial rhythm became irregular. Below 20 degrees C, atrial depolarization disappeared. Chronotropic responses to norepinephrine were suppressed at decreased temperatures, not only with respect to maximum PP shortening but also to the threshold dose for inducing sinus acceleration. Overdrive suppression was not influenced significantly by decreasing temperature. These results indicate that a temperature decrease causes suppression of SA nodal pacemaker activity, although the SA node continues to function regularly until about 25 degrees C.

Animals↗

Chronotropic responses to experimental ischemia of the canine sino auricular node.

(1) Using isolated, blood-perfused atrium preparation of dogs, the effect of ischemia on sinus rate was studied in ten preparations. Cessation of atrial perfusion usually induced gradual deceleration of the sinus rate which was not blocked by atropine. Occasionally, brief and slight sinus acceleration was initially observed in three of ten atrium preparations. This positive chronotropic effect was not blocked by a beta-adrenoceptor blocking agent, propranolol. (2) In every preparation, just after release of occlusion, there was an initial profound sinus deceleration, occasionally followed by oscillatory changes in sinus rate. (3) The chronotropic response pattern induced by temporary occlusion and release of the sinus node artery was not influenced by propranolol, phenoxybenzamine or atropine treatment. (4) These results suggest that ischemia exerts its principal effect directly on the sino auricular node pacemaker cells, rather than on neighboring nerve endings.

Acetylcholine↗

Atrial pacemaker leads compared.

In order to analyze the impact of different polarity and electrode designs on the acute pacing and sensing characteristics of pacemaker leads, 80 patients with complete heart block or sinus node dysfunction undergoing pacemaker implantation received eight different leads from five manufacturers. Once the leads were positioned, volt and current thresholds, P wave, peak-to-peak, and slew rate were assessed prospectively. There was no statistically significant difference between acute pacing thresholds, sensing characteristics, or unipolar and bipolar pacing thresholds. Active fixation leads allow atrial mapping and lead placement in areas generally inaccessible to tined tip leads. This is an advantage, especially for patients with a history of open heart surgery.

Electrodes, Implanted↗

Transcatheter electrical AV junction ablation: predictors of success.

The initial and long-term results of transcatheter electrical ablation in 29 patients with drug-refractory supraventricular tachyarrhythmias were analyzed. Ablation was immediately successful (defined as induction of chronic complete heart block) in 25 patients (86.2%). Among the group in whom ablation was unsuccessful, there were more patients with ectopic atrial tachycardia and a higher incidence of narrow QRS escape rhythm following the initial ablation. A His amplitude equal to or greater than 0.3 mV was correlated with success. Complications of ablation included deep venous thrombosis and ventricular arrhythmias. Post-ablation stress testing was superior to ambulatory monitoring in identifying early return of atrioventricular conduction.

Adult↗

Catheter ablation for recurrent ventricular tachycardia.

A 78-year-old man had sustained ventricular tachycardia refractory to drug therapy. An antitachycardia pacemaker and a cardioverter-defibrillator were implanted. It was suspected that rate crossover was occurring between his sinus rhythm and his antitachycardia pacemaker detection rate. He also had frequent discharges from his implantable cardioverter-defibrillator. Because of these problems, he was considered a candidate for catheter ablation treatment of his ventricular tachycardia. The procedure was completed successfully and long-term follow-up has been uneventful. Catheter ablation is recommended as a treatment option for patients who have ventricular tachycardia that is refractory to drug therapy and combined-device therapy, and who have rate crossover.

Aged↗

The Maze procedure: surgical therapy for refractory atrial fibrillation.

Although atrial fibrillation is well tolerated by most patients, in some patients the consequences may be severe. The Maze procedure is a new open-heart operation that creates a carefully designed maze of incisions in the atrial myocardium; this maze then acts as an electrical conduit to channel atrial impulses from the sinoatrial node to the atrioventricular node. The Maze procedure has been shown to restore sinus rhythm and atrial systole (thus reducing the risk of thromboembolism), improve hemodynamics, alleviate palpitations, and eliminate the need for antiarrhythmic and anticoagulant drugs. We describe our first patient to undergo this operation.

Aged↗