Biomedical subjects

S R Shorofsky

Publications and source records attributed to S R Shorofsky.

At least 37 records · Page 2Linked to original sources

PubMed1998

Ca2+ sparks triggered by patch depolarization in rat heart cells.

The goal of this study was to examine the relationship between Ca2+ entry through L-type Ca2+ channels and local [Ca2+]i transients (Ca2+ sparks) in single rat cardiac ventricular cells. L-type Ca2+ channels were activated by depolarization of cell-attached membrane patches, and [Ca2+]i was measured simultaneously as fluo 3 fluorescence using laser scanning confocal microscopy. Patch depolarization with Ca2+ as the charge carrier (10 or 110 mmol.L(-1)) significantly increased the probability of the occurrence of Ca2+ sparks (Ca2+ spark rate) only in the volume of cytoplasm located immediately beneath the membrane patch (basal Ca2+ spark rate, 119 Ca2+ sparks.cell(-1).s(-1); patch depolarization Ca2+ spark rate, 610 Ca2+ sparks.cell(-1).s(-1); P<.005). With Ba2+ in the pipette solution (10 mmol.L(-1)), patch depolarization was not associated with an increased Ca2+ spark rate at the position of the pipette or at any other sites distant from the pipette. Therefore, Ca2+ entry and not voltage per se was a necessary event for the occurrence of Ca2+ sparks. Under identical experimental conditions, patch depolarization experiments opened single L-type Ca2+ channels with a single-channel conductance of 19 pS with Ba2+ as the charge carrier. Although single-channel openings could not be resolved when Ca2+ was the charge carrier, ensemble averages yielded an inward current of up to 0.75 pA. The results suggest that voltage-activated Ca2+ entry through one or a small number of L type Ca2+ channels triggers the release of Ca2+ only from the sarcoplasmic reticulum in direct proximity to those L-type Ca2+ channels. The relatively low probability of triggering Ca2+ sparks may have resulted from some alteration of excitation-contraction coupling associated with the technique of the cell-attached patch clamp.

Animals↗

PubMed1998

Alterations in calcium handling in cardiac hypertrophy and heart failure.

There is conflicting data concerning the effects of cardiac hypertrophy and failure on L-type Ca2+ channel density, the amplitude of the intracellular Ca2+ transients, and the characteristics of Ca2+ sparks. These discrepancies are probably due to multiple factors. First, the effects of cardiac hypertrophy on channel expression and cell adaptation are model dependent. Even within the same species, the mechanisms by which cardiac hypertrophy and heart failure are generated (genetic alteration, pressure overload, volume overload, high rate pacing, etc.) influence the results obtained. Second, with many animal models and diseased human hearts, the disease process is not uniformly distributed throughout the myocardium. Third, the effects on L-type Ca2+ channel behavior and SR function clearly depend on the extent of disease expression. Myocardial contractility increases with cardiac hypertrophy whereas it decreases with heart failure. Thus, it is difficult to compare results from different models of hypertrophy and heart failure at different stages of disease. More consistent data is likely to be obtained from longitudinal studies using a single animal model of disease. The challenge before us is to develop animal models that mimic human disease, which can be studied longitudinally during the progression of the disease process. This approach coupled with continued improvement in Ca2+ imaging and a greater understanding of normal E-C coupling, will enable us to identify precisely the abnormalities in E-C coupling that occur with the development of cardiac hypertrophy and heart failure and define the appropriate treatment modalities.

Calcium↗

PubMed1998

Comparison of single- and dual-coil active pectoral defibrillation lead systems.

OBJECTIVES: The purpose of this study was to compare defibrillation thresholds with lead systems consisting of an active left pectoral electrode and either single or dual transvenous coils. BACKGROUND: Lead systems that include an active pectoral pulse generator reduce defibrillation thresholds and permit transvenous defibrillation in nearly all patients. A further improvement in defibrillation efficacy is desirable to allow for smaller pulse generators with a reduced maximal output. METHODS: This prospective study was performed in 50 consecutive patients. Each patient was evaluated with two lead configurations with the order of testing randomized. Shocks were delivered between the right ventricular coil and either an active can alone (single coil) or an active can with the proximal atrial coil (dual coil). The right ventricular coil was the cathode for the first phase of the biphasic defibrillation waveform. RESULTS: Delivered energy at the defibrillation threshold was 10.1+/-5.0 J for the single-coil configuration and 8.7+/-4.0 J for the dual-coil configuration (p < 0.02). Moreover, 98% of patients had low (<15 J) thresholds with the dual-coil lead system, compared with 88% of patients with the single-coil configuration (p=0.05). Leading edge voltage (p < 0.001) and shock impedance (p < 0.001) were also decreased with the dual-coil configuration, although peak current was increased (p < 0.001). CONCLUSIONS: A dual-coil, active pectoral lead system reduces defibrillation energy requirements compared with a single-coil, unipolar configuration.

Aged↗

PubMed1998

The effect of delivered energy on defibrillation shock impedance.

The impedance of internal defibrillator shocks is an important determinant of defibrillation efficacy. To assess the effect of delivered energy on impedance, we studied 97 patients with 4 different lead systems. The lead systems evaluated were two epicardial patches, a hybrid system of a patch and right atrial coil, a dual coil transvenous lead and a transvenous lead with a subcutaneous patch. Impedances were measured for 6 shock energies between 0.1 and 30 J. Shock impedance increased at low energies for all lead systems (p < 0.001), although the rate of increase varied markedly between systems. The energy factor (FE), which is the ratio of impedances for the 0.1 and 10 J shocks, was least for the platinum transvenous lead (1.2 +/- 0.02) and greatest for the titanium hybrid lead (4.2 +/- 0.2). Reversing the polarity of the hybrid lead markedly attenuated the impedance rise. These findings indicate that there is at least a modest rise (20%) of shock impedance at very low delivered energies. The largest increases noted with titanium lead systems are primarily due to polarization. Titanium transvenous leads should be avoided when low energy shocks are utilized such as for the cardioversion of ventricular tachycardia or atrial fibrillation.

Arrhythmias, Cardiac↗

PubMed1998

A comparison of pectoral and abdominal transvenous defibrillator implantation: analysis of costs and outcomes.

Traditionally cardioverter-defibrillator implantation was performed by surgeons under general anesthesia. However, with advances in lead and pulse generator technology, the surgical implantation technique has been simplified and routine pectoral pulse generator placement without general anesthesia is now possible. To assess the economic benefit of pectoral implantation, we analyzed 43 consecutive initial transvenous defibrillator implantations. The patients were grouped according to whether the implant was abdominal by a surgeon in the operating room (n = 23) or pectoral by an electrophysiologist in a laboratory (n = 20). The duration of hospitalization was significantly longer in the operating room than in the laboratory group (8.1 +/- 3.4 vs 5.8 +/- 2.4 days, p = 0.01), which was due primarily to the postoperative stay which averaged 1.9 days longer. Total costs were $40,274 +/- 6,861 for the operating room cohort and $32,546 +/- 3,634 for the lab group (p < 0.001). This reduction was due to a 32% lowering of professional costs and an 18% lowering of facility costs. We conclude that pectoral defibrillator implantation is cost effective and results in significant reductions of hospital stay.

Abdominal Muscles↗

PubMed1998

Inappropriate shocks from implanted cardioverter defibrillators caused by sensing of diaphragmatic myopotentials.

Inappropriate shocks remain one of the major problems associated with the use of implantable cardioverter defibrillators (ICD). We describe 3 patients who had inappropriate shocks due to oversensing of diaphragmatic myopotentials. In all 3, oversensing could be demonstrated during deep inspiration or Valsalva maneuver. The problem was remedied in one by insertion of a separate rate sensing lead in the right ventricular outflow tract, in the second by decreasing the rate of antibradycardia pacing of the ICD, and in the third by decreasing the sensitivity of the ICD. We conclude that the possibility of sensed diaphragmatic myopotentials should be considered at the time of ICD implant so that appropriate preventive measures can be taken.

Aged↗

PubMed1998

Temporal stability of defibrillation thresholds with an active pectoral lead system.

INTRODUCTION: Monophasic defibrillation thresholds rise over time with a variety of lead systems. These chronic changes are attenuated or eliminated by biphasic waveforms, although the effect appears dependent upon the lead system. With the downsizing of pulse generator size to allow for routine pectoral implantation, active can lead systems have now become standard. However, the temporal stability of such lead systems has not been evaluated previously. METHODS AND RESULTS: This study was a prospective assessment of the changes of active pectoral defibrillation thresholds over time. Thresholds were measured at implant, predischarge, and at a mean follow-up of 50 days in 46 patients with a uniform testing protocol and shock polarity. The lead system was a dual-coil Endotak DSP lead with an active pectoral pulse generator. Defibrillation thresholds were 9.9+/-5.5 J at implantation, 8.5+/-6.0 J predischarge, and 7.6+/-5.5 J at follow-up (ANOVA, P = 0.007). Moreover, only two patients developed an increased threshold > 5 J, and no patient had an inadequate safety margin at follow-up. CONCLUSION: These results indicate that active pectoral defibrillation thresholds are stable over the first 2 months postimplantation and question the need for routine serial defibrillation threshold testing.

Aged↗

PubMed1998

Effect of shock polarity on biphasic defibrillation thresholds using an active pectoral lead system.

INTRODUCTION: The downsizing of implantable defibrillator pulse generators has made pectoral placement routine. A further reduction of defibrillation thresholds (DFTs) may simplify implantation defibrillation testing and allow for smaller, lower output pulse generators while maintaining an adequate defibrillation safety margin. One factor that may affect defibrillation efficacy is shock polarity. METHODS AND RESULTS: Sixty consecutive patients undergoing dual-coil, active left pectoral defibrillator implantation were evaluated. Paired, biphasic DFTs were measured in normal (RV apex = cathode) and reverse (RV apex = anode) polarity with order of testing randomized. Reverse polarity conferred a 15% reduction of mean DFTs (8.5 +/- 5.0 J normal, 7.2 +/- 4.6 J reverse polarity, P = 0.02). The effect of polarity appeared most pronounced among the patients with a high DFT (> or = 15 J) resulting in a 31% reduction with reverse polarity (16.7 +/- 2.5 J normal, 11.5 +/- 5.9 J reverse, P = 0.03). CONCLUSION: Reversing shock polarity results in significantly lower biphasic DFTs with an active pectoral lead system, particularly in the subgroup of patients with a high normal polarity threshold. Reversing polarity in these patients may simplify acute defibrillation testing and allow for lower output devices.

Arrhythmias, Cardiac↗

PubMed1998

Effect of heart rate on T wave alternans.

INTRODUCTION: T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial. METHODS AND RESULTS: This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 +/- 0.7 microV, 1.6 +/- 1.9 microV, and 2.4 +/- 2.1 microV in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%. CONCLUSION: These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.

Cardiac Pacing, Artificial↗

PubMed1997

Comparison of power- and temperature-guided radiofrequency modification of the atrioventricular node. Polaris Investigator Group.

The purpose of this study was to compare the performance and clinical outcome of radiofrequency ablation of the substrate of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) when guided by power output or temperature monitoring. Two sequential multicenter studies of power-controlled and open-loop, temperature-controlled radiofrequency ablation were analyzed in 171 patients undergoing AV node modification for the treatment of AVNRT. After successful ablation of AVNRT, complete elimination of slow AV node pathway function was accomplished more often with than without temperature monitoring (92% vs 69%, p = 0.005). Greater power was delivered to each patient with than without temperature monitoring (median 47 W, range 10 to 57, vs median 35 W, range 5 to 68, p = 0.001). Acute elimination of tachycardia (100% vs 96%), 3-month recurrence (6% vs 8%), procedural times (162 vs 170 minutes), fluoroscopy times (24.6 vs 29.5 minutes), complications (6% vs 3%), and catheter removals to check for coagulum (8% vs 6%) did not differ between patients treated with and without temperature monitoring, respectively. Power- and temperature-controlled radiofrequency techniques are highly successful with low complication rates for slow pathway ablation. Temperature monitoring may allow the safe delivery of more power, and the more complete elimination of slow AV node pathway function.

Atrioventricular Node↗

PubMed1997

Tetrodotoxin-blockable calcium currents in rat ventricular myocytes; a third type of cardiac cell sodium current.

1. Whole-cell patch clamp currents from freshly isolated adult rat ventricular cells, recorded in external Ca2+ (Ca2+o) but no external Na+ (Na+o), displayed two inward current components: a smaller component that activated over more negative potentials and a larger component (L-type Ca2+ current) that activated at more positive potentials. The smaller component was not generated by Ca2+ channels. It was insensitive to 50 microM Ni2+ and 10 microM La3+ but suppressed by 10 microM tetrodotoxin (TTX). We refer to this component as ICa(TTX). 2. The conductance-voltage, g(V), relation in Ca2+o only was well described by a single Boltzmann function (half-maximum potential, V1/2, of -44.5; slope factor, k, of -4.49 mV, means of 3 cells). g(V) in Ca2+o plus Na+o was better described as the sum of two Boltzmann functions, one nearly identical to that in Ca2+o only (mean V1/2 of -45.1 and k of -3.90 mV), and one clearly distinct (mean V1/2 of -35.6 and k of -2.31 mV). Mean maximum conductance for ICa(TTX) channels increased 23.7% on adding 1 mM Na+o to 3 mM Ca2+o. ICa(TTX) channels are permeable to Na+ ions, insensitive to Ni2+ and La3+ and blocked by TTX. They are Na+ channels. 3. ICa(TTX) channels are distinct from classical cardiac Na+ channels. They activate and inactivate over a more negative range of potentials and have a slower time constant of inactivation than the classical Na+ channels. They are also distinct from yet another rat ventricular Na+ current component characterized by a much higher TTX sensitivity and by a persistent, non-fast-inactivating fraction. That ICa(TTX) channels activate over a more negative range of potentials than classical cardiac Na+ channels suggests that they may be critical for triggering the ventricular action potential and so of importance for cardiac arrhythmias.

Animals↗

PubMed1997

Strength-duration relationship for human transvenous defibrillation.

BACKGROUND: One of the basic characteristics of electrical defibrillation is the strength-duration relationship, or the effect of pulse width on defibrillation efficacy. This relationship is important for understanding the mechanism of defibrillation and for the design of optimal waveforms. However, a detailed evaluation of the strength-duration relationship for human transvenous defibrillation has not been performed previously. METHODS AND RESULTS: This was a prospective study of 29 patients undergoing initial defibrillator implantation with a uniform dual coil, transvenous lead. In each patient defibrillation thresholds were measured for either short (2, 3, 4, 6 ms) or long (6, 12, 18 ms) pulse durations, with the order of testing randomized. The shock waveform was a truncated monophasic pulse from a capacitor of 150 microF. The leading edge voltage at defibrillation threshold was 566+/-100 V for 2-ms pulses. Voltages declined exponentially with increasing pulse width reaching an asymptote by 6 ms (451+/-68 V, P<.05). Defibrillation threshold voltage was insensitive to longer pulse widths. Stored energy at defibrillation threshold showed a similar relationship with pulse width. In contrast, mean current decreased monotonically over the full range of pulse durations evaluated, and there was no evidence of a rheobase. CONCLUSIONS: The shape of the strength-duration curve and the lack of rheobase current indicate a fundamental difference between cardiac stimulation and defibrillation. The relationship between pulse duration and defibrillation threshold voltage or stored energy is well modeled by a parallel capacitor resistor circuit with a time constant of 5.3 ms.

Aged↗

PubMed1997

Lead system optimization for transvenous defibrillation.

Lead systems that include an active pectoral shell reduce defibrillation thresholds and permit transvenous defibrillation in nearly all patients. A further improvement in defibrillation efficacy is desirable to allow for smaller pulse generators with a reduced maximum output. Accordingly, the purpose of this study was to compare defibrillation thresholds with multiple transvenous lead systems including those with an active pectoral shell to determine which system would optimize defibrillation energy requirements. This prospective study was performed on 21 consecutive patients. Each subject was evaluated with 3 lead configurations with the order of testing randomized. The configurations were a dual coil transvenous lead (lead), the distal right ventricular coil and pectoral pulse generator shell (unipolar), and all 3 components (triad). The right ventricular coil was the cathode for the first phase of the biphasic defibrillation waveform. Delivered energy at defibrillation threshold was 11.2 +/- 3.4 J for the lead configuration, 10.1 +/- 5.2 J for the unipolar configuration, and 7.8 +/- 3.6 J for the triad configuration (p <0.01). Leading edge voltage (p <0.01) and shock impedance (p <0.001) were also decreased for the triad configuration compared with the lead or unipolar configurations, whereas peak current was minimized with the unipolar configuration (p <0.01). We conclude that the combination of a dual coil, transvenous lead and an active pectoral shell reduces defibrillation energy requirements compared with either the lead alone or unipolar configuration. Moreover, the defibrillation thresholds were < or =15 J in all patients using the triad lead system.

Defibrillators, Implantable↗

PubMed1997

Effect of biphasic waveforms on transvenous defibrillation thresholds in patients with coronary artery disease.

This study is a prospective, randomized comparison of monophasic and biphasic defibrillation thresholds in 19 patients with a single transvenous lead. Despite using reverse polarity and optimal tilts for the monophasic waveform, the defibrillation threshold was reduced with biphasic shocks from 15.8 +/- 11.3 to 11.5 +/- 6.1 (p <0.05) with comparable reductions of leading edge voltage and current.

Aged↗

PubMed1997

Induction of atrial fibrillation with low-energy defibrillator shocks in patients with implantable cardioverter defibrillators.

In a population of 151 consecutive patients who received an implantable cardioverter defibrillator, we found that atrial fibrillation was induced by low-energy shocks in 19% and was most common in patients with lead systems that included a right atrial electrode. Our finding that there was a fixed relation between the energy required to fibrillate (< or = 3 J) and defibrillate (> 3 J) suggests the presence of an upper limit of vulnerability in the human atrium.

Aged↗

PubMed1997

Comparison of class Ia/Ib versus class III antiarrhythmic drugs for the suppression of inducible sustained ventricular tachycardia associated with coronary artery disease.

Previous studies suggest that class Ia drugs are ineffective in suppression of sustained ventricular tachycardia by programmed stimulation. More favorable results have been described with combinations of Ia and Ib drugs and also with class III antiarrhythmic drugs, but there have been no direct comparisons between these 2 regimens. The present study was undertaken to compare the electrophysiologic efficacy and predictors of success of these 2 regimens in patients with ischemic heart disease and inducible sustained monomorphic ventricular tachycardia. The population consisted of 136 patients with documented coronary artery disease. All had sustained monomorphic ventricular tachycardia inducible during baseline electrophysiologic study and following intravenous procainamide. Follow-up studies were performed with a combination of oral class Ia and Ib or class III antiarrhythmic drugs. A positive response was the inability to induce a sustained ventricular arrhythmia with up to 3 extrastimuli at 2 right ventricular pacing sites. Response rates were 13% for Ia/Ib combination and 19% for class III agents (p = 0.40). Congestive heart failure differentially affected response rates. Only 8% of those responding to Ia/Ib therapy had heart failure compared with 59% of responders to class III (p <0.01). Multivariate analysis identified heart failure (RR 12.2, p = 0.03) as the only parameter with independent predictive value of response to Ia/Ib therapy. These results indicate that congestive heart failure is a potent predictor of a negative response to a combination of class Ia and Ib antiarrhythmic drugs. In this population, class III drugs or nonpharmacologic therapy should be considered as initial treatment.

Aged↗

PubMed1997

Clinical predictors of transvenous biphasic defibrillation thresholds.

Transvenous lead systems have become routine for defibrillator placement. However, previous studies of clinical predictors of an adequate nonthoracotomy defibrillation threshold (DFT) evaluated monophasic waveforms or more complex lead systems, including subcutaneous patches. Accordingly, this study is a prospective evaluation of the predictors of an adequate biphasic DFT in 114 consecutive patients undergoing cardioverter-defibrillator implantation with a single transvenous lead. For each subject, 38 parameters were assessed, including standard demographic, electrocardiographic, echocardiographic, and radiographic measurements. An adequate DFT (< or =20 J) was achieved in 92% of patients. Multivariable analysis revealed 2 independent factors predictive of a high threshold: echocardiographic measurements of left ventricular dilation (odds ratio = 0.16, 95% confidence interval 0.05 to 0.53, p = 0.003) and body size (odds ratio = 0.36, 95% confidence interval 0.17 to 0.73; p = 0.005). No patient with a normal left ventricular end-diastolic dimension had a high DFT, whereas 14% (9 of 66) of those with left ventricular dilation had elevated thresholds. When the DFT cutoff was lowered to 15 J, as is necessary with some downsized pulse generators, an adequate threshold was observed in 84% of patients and the same 2 independent predictors of high thresholds were found. These results indicate that an adequate transvenous DFT can be predicted from simple clinical parameters.

Aged↗

PubMed1997

The acute hemodynamic effects of right ventricular septal pacing in patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

To assess the hemodynamic effects of right ventricular septal pacing in patients with severe chronic heart failure, we studied 13 patients during intrinsic rhythm and with pacing in the VDD mode at atrioventricular delays of 100 to 200 ms. There was no improvement of any hemodynamic parameter measured with pacing, even in the subgroup of patients with prolonged PR intervals.

Atrioventricular Node↗