Influence of polarity reversal on defibrillation success with biphasic shocks and a transvenous/subcutaneous defibrillator system in a porcine animal model

Clinical studies show that polarity reversal affects defibrillation success in transvenous monophasic defibrillators. Current devices use biphasic shocks for defibrillation. We investigated in a porcine animal model whether polarity reversal influences defibrillation success with biphasic shocks. In nine anesthetized, ventilated pigs, the defibrillation efficacy of biphasic shocks (14.3 ms and 10.8 ms pulse duration) with "initial polarity" (IP, distal electrode = cathode) and "reversed polarity" (RP, distal electrode = anode) delivered via a transvenous/subcutaneous lead system was compared. Voltage and current of each defibrillating pulse were recorded on an oscilloscope and impedance calculated as voltage divided by current. Cumulative defibrillation success was significantly higher for RP than for IP for both pulse durations (55% vs 44%, P = 0.019) for 14.3 ms (57% vs 45%, P < 0.05) and insignificantly higher for 10.8 ms (52% vs 42%, P = ns). Impedance was significantly lower with RP at the trailing edge of pulse 1 (IP: 44 +/- 8.4 vs RP: 37 +/- 9.3 with 14.3 ms, P < 0.001 and IP: 44 +/- 6.2 vs RP: 41 +/- 7.6 omega with 10.8 ms, P < 0.001) and the leading edge of pulse 2 (IP: 37 +/- 5 vs RP: 35 +/- 4.2 omega with 14.3 ms, P = 0.05 and IP: 37.5 +/- 3.7 vs RP: 36 +/- 5 omega with 10.8 ms, P = 0.02). In conclusion, in this animal model, internal defibrillation using the distal coil as anode results in higher defibrillation efficacy than using the distal coil as cathode. Calculated impedances show different courses throughout the shock pulses suggesting differences in current flow during the shock.     

Effect of ventricular dilatation on defibrillation threshold in the isolated perfused rabbit heart

INTRODUCTION: Ventricular dilatation has important electrophysiologic effects, but its effect on ventricular defibrillation threshold (DFT) is unknown. METHODS AND RESULTS: A fluid-filled, latex balloon was placed in the left ventricular cavity of 19 isolated rabbit hearts. In each experiment, an undilated volume (equivalent to a left ventricular end-diastolic pressure of approximately 0 mmHg) was compared to a dilated volume achieved by adding 1.0 mL of saline (n = 10) or 5% dextrose (n = 9) to the intracavitary balloon. Left ventricular effective refractory period (ERP) and DFT were determined at each volume. Defibrillation was attempted with a monophasic shock delivered between a patch electrode positioned over the posterior left ventricle (cathode) and a metallic aortic cannula (anode). DFT was determined using a modified "down/up" protocol with 10 V steps. Ventricular dilatation increased the left ventricular end-diastolic pressure from 0 +/- 0.5 mmHg to 35 +/- 3 mmHg (P < 0.001), decreased the average left ventricular ERP 15% (from 116 +/- 3 msec to 99 +/- 3 msec; P < 0.001), and increased the average DFT 30% (from 96 +/- 4 V to 125 +/- 7 V; P < 0.001). In one third of experiments, the dilated DFT was > or = 150% of the DFT at zero volume. The mechanism of the observed increase in DFT is unknown but may be related to the decrease in refractoriness observed with ventricular dilatation. CONCLUSION: Acute ventricular dilatation in this model increased DFT an average of 30%, an effect not previously described. This observation may have implications for patients with implantable cardioverter defibrillators.     

Clinical shock tolerability and effect of different right atrial electrode locations on efficacy of low energy human transvenous atrial defibrillation using an implantable lead system

OBJECTIVES: The objectives of this study were 1) to evaluate the effect of different right atrial electrode locations on the efficacy of low energy transvenous defibrillation with an implantable lead system; and 2) to qualitate and quantify the discomfort from atrial defibrillation shocks delivered by a clinically relevant method. BACKGROUND: Biatrial shocks result in the lowest thresholds for transvenous atrial defibrillation, but the optimal right atrial and coronary sinus electrode locations for defibrillation efficacy in humans have not been defined. METHODS: Twenty-eight patients (17 men, 11 women) with chronic atrial fibrillation (AF) (lasting > or = 1 month) were studied. Transvenous atrial defibrillation was performed by delivering R wave-synchronized biphasic shocks with incremental shock levels (from 180 to 400 V in steps of 40 V). Different electrode location combinations were used and tested randomly: the anterolateral, inferomedial right atrium or high right atrial appendage to the distal coronary sinus. Defibrillation thresholds were defined in duplicate by using the step-up protocol. Pain perception of shock delivery was assessed by using a purpose-designed questionnaire; sedation was given when the shock level was unacceptable (tolerability threshold). RESULTS: Sinus rhythm was restored in 26 of 28 patients by using at least one of the right atrial electrode locations tested. The conversion rate with the anterolateral right atrial location (21 [81%] of 26) was higher than that with the inferomedial right atrial location (8 [50%] of 16, p < 0.05) but similar to that with the high right atrial appendage location (16 [89%] of 18, p > 0.05). The mean defibrillation thresholds for the high right atrial appendage, anterolateral right atrium and inferomedial right atrium were all significantly different with respect to energy (3.9 +/- 1.8 J vs. 4.6 +/- 1.8 J vs. 6.0 +/- 1.7 J, respectively, p < 0.05) and voltage (317 +/- 77 V vs. 348 +/- 70 V vs. 396 +/- 66 V, respectively, p < 0.05). Patients tolerated a mean of 3.4 +/- 2 shocks with a tolerability threshold of 255 +/- 60 V, 2.5 +/- 1.3 J. CONCLUSIONS: Low energy transvenous defibrillation with an implantable defibrillation lead system is an effective treatment for AF. Most patients can tolerate two to three shocks, and, when the starting shock level (180 V) is close to the defibrillation threshold, they can tolerate on average a shock level of 260 V without sedation. Electrodes should be positioned in the distal coronary sinus and in the high right atrial appendage to achieve the lowest defibrillation threshold, although other locations may be suitable for certain patients.     

Effects of electrode configuration on psychophysical strength-duration functions for single biphasic electrical stimuli in cats

The interface between electrode and neural target tissue is thought to influence certain characteristics of neural and behavioral responses to electrical stimulation of the auditory system. At present, the biophysical properties of this interface are not well understood. Here the effects of biphasic phase duration and electrode configuration on psychophysical threshold in response to electrical stimulation in cats are described. Five cats were trained to respond to acoustic stimuli using food as a reward in an operant reinforcement paradigm. After training, the animals were unilaterally deafened and implanted with a multicontact intracochlear electrode array. Thresholds for single presentations of biphasic current pulses were measured as a function of phase duration and electrode arrangement. Statistical analyses of the data indicated that strength-duration function slopes between 200 and 1600 microseconds/phase were significantly different for the different electrode configurations and, overall, were unrelated to the absolute level of the strength-duration function (i.e., were independent of absolute threshold). For all subjects, the slope of this function for intermediate pulse durations was dependent on electrode configuration and most shallow for radial-bipolar configurations (-3.4 dB/doubling), was steepest for monopolar arrangements (-5.9 dB/doubling), and was intermediate for longitudinal-bipolar pairings. (-4.4 dB/doubling). Slopes for both shorter and longer phase duration stimuli were not significantly different. The underlying mechanisms for these effects may include, or be a combination of altered electrical field patterns, integrated activity across multiple fibers, and stochastic behavior of individual auditory neurons to electrical stimulation.     

Importance of electrode conductive surface area and edge effects on ventricular defibrillation efficacy

INTRODUCTION: The role of edge effects and electrode surface area of the right ventricular (RV) transvenous lead (TVL) on defibrillation efficacy is unknown. METHODS AND RESULTS: Defibrillation threshold (DFT) testing was conducted randomly in 12 dogs using ring electrode leads in an RV/SVC (superior vena cava) or RV/SVC/patch system. The leads (RV-4, RV-8t, RV-8, RV-15) had electrode surface areas of 20%, 20%, 40%, and 70%, respectively. A computer model predicted the magnitude of electrode surface current (RV-8t > RV-4 > RV-8 > RV-15) and the potential distribution (PD) at four sites: electrode surface (site a) and at 2 mm (b), 4 mm (c), and 8 mm (d) away from the surface. Despite different near-field PDs (sites a, b, c), PDs were nearly identical at site d. Resistance decreased as the surface area increased. DFT energy for the RV-15 lead was lower than the RV-4 and RV-8t. There was no difference between energy requirements for the RV-15 and RV-8 leads. No difference was found in DFT current for each lead. Comparison of the RV-8t and RV-4 leads showed no difference in DFT energy despite a lower resistance and a greater number of edges. CONCLUSIONS: Increasing the RV TVL surface area lowered the resistance. However, surface area coverages > or = 40% did not lower DFT energy. No significant change in DFT current occurred despite different predicted near-field current densities. PDs were nearly identical 8 mm from the electrode surface. Thus, the far-field current density appears to play a more important role in determining defibrillation success.     

Effect of skin electrode location on radiofrequency ablation lesions: an in vivo and a three-dimensional finite element study

To elucidate the mechanism of ischemia-induced signal transduction in vivo, we investigated the effect of the targeted disruption of the alpha and delta isoforms of the cAMP-responsive element-binding protein (CREB) on c-fos and heatshock protein (hsp) 72 gene induction. Permanent focal ischemia was induced by occlusion of the middle cerebral artery of the CREB mutant mice (CREB(-/-), n = 5) and the wild-type mice (n = 6). Three hours after onset of ischemia, the neurologic score was assessed and pictorial measurements of ATP and cerebral protein synthesis (CPS) were carried out to differentiate between the ischemic core (where ATP is depleted), the ischemic penumbra (where ATP is preserved but CPS is inhibited), and the intact tissue (where both ATP and CPS are preserved). There were no significant differences in neurologic score or in ATP, pH, and CPS between the two groups, suggesting that the sensitivity of both strains to ischemia is the same. Targeted disruption of the CREB gene significantly attenuated c-fos gene induction in the periischemic ipsilateral hemisphere but had no effect on either c-fos or hsp72 mRNA expression in the penumbra. The observations demonstrate that CREB expression, despite its differential effect on c-fos, does not modulate acute focal ischemic injury.     

脉冲电场处理对钢的凝固组织和元素分布的影响

通过改变脉冲电场的电压对钢液进行处理,研究了脉冲电场处理对钢液凝固元素迁移特性和晶粒细化的影响.利用ImageJ软件统计分析了试样的晶粒数和晶粒分布,利用原位分析仪分析了钢中主要元素C、Si、Mn、P和S的分布与偏析情况,探讨了不同电压下脉冲电场对钢液凝固过程元素迁移特性的影响.实验结果表明,随着脉冲处理电压升高,晶粒明显得到细化,钢中元素Si、Mn和P具有相似的分布,而P和S具有相反的分布特性.     

Effect of the addition of an abdominal hot can cardioverter/defibrillator pulse generator on the defibrillation energy requirements in a single-lead endocardial defibrillation system

AIMS: The effects of a cardioverter/defibrillator system with an electrically active generator can, applied without recourse to thoracotomy, have not been investigated in the abdominal position in humans. The purpose of this acute clinical study was to evaluate the defibrillation efficacy of an abdominally positioned hot can electrode in connection with a single lead endocardial defibrillation system. PATIENTS AND METHODS: Thirty consecutive patients undergoing implantation of a cardioverter/defibrillator or pulse generator replacement were enrolled in this study Each patient received an integrated, tripolar single-lead system. This was tested using an asymmetrical biphasic defibrillation waveform with constant energy delivery. Defibrillation energy, peak voltage, peak current and impedance were compared between two electrode configurations: (A) in this configuration the distal right ventricular coil was negative and the proximal coil positive; (B) in this configuration the distal right ventricular coil was negative and the proximal coil and the abdominal hot can (65 ccm), as common anode, were positive. Defibrillation threshold testing started at 15 J with stepwise energy reduction (10 J, 8 J, 5 J and 3 J) until defibrillation was ineffective. RESULTS: Compared to the single-lead configuration, the abdominal hot can configuration revealed at 17.5% reduction in defibrillation energy requirements (8.6 J +/- 4.3 J vs 10.43 J +/- 3.9 J; P = 0.041), a 15.7% reduction in peak voltage (308.6 V +/- 63 V vs 365.3 V +/- 68 V; P = 0.003), and a 21.6% reduction in impedance (41.1 omega +/- 6.3 omega vs 52.4 omega +/- 6.6 omega; P < 0.001). Peak current showed a significant increase during hot can testing of 8.2% (7.2 A +/- 1.8 A vs 7.8 A +/- 2.2 A; P = 0.16). CONCLUSION: An abdominally placed hot can pulse generator lowered defibrillation energy requirements in patients with an endocardial defibrillation lead system.     

Effect of surface modifiers on the electrode reactions and conformation of cytochrome c3 adsorbed on a silver electrode

Higher rates of left-handedness and atypical lateralization in schizophrenics paired with findings of morphological abnormalities in cerebral asymmetry suggest that the normal patterns of hemisphere specialization for processing verbal and spatial information may be anomalous in schizophrenics. The small number of studies that have addressed this question have produced inconsistent findings and varied with subtype diagnosis, gender, type of task employed, task difficulty, and control of handedness. Conflicting research findings also may be due to confounding from the heterogeneity of the schizophrenic construct and variability in clinical symptoms across patients. The present study was designed to control for factors that may have confounded earlier studies. Because the study used perceptual measures, the relationship between symptoms of perceptual aberration and hemisphere advantages was examined using Chapman et al.'s (1978) Perceptual Aberration Scale (PAS). Fifteen male schizophrenic patients and 14 male controls were administered tachistoscopic letter and facial recognition go/no-go reaction time tasks. Left hemisphere advantages were found for both controls and schizophrenics on the letter task. Right hemisphere advantages were found for controls on the facial task but not schizophrenics. Instead, a strong negative correlation was found between schizophrenics' PAS scores and hemisphere advantages (r = -0.685, p < 0.007). Further analysis identified a subgroup of schizophrenics with perceptual aberration who exhibited reversed left hemisphere advantages that increased as the PAS scores increased. Additional research is needed to determine whether this subgroup of schizophrenics constitutes a meaningful subtype with a distinct disease process that disrupts the development of normal cerebral lateralization. The findings provide further evidence for the importance of examining relationships between schizophrenics' performance on cognitive measures and their symptom patterns.     

Effect of switch configuration on the operation of a switch matrix.

In a series of 3 experiments the speed and accuracy of switch-matrix operations were determined for 5 different matrix configurations. Factors influencing performance included switch orientation (whether row or column), reach distance, and the type of symbol with which the switches were labeled. Response time was the only important performance measure. Error rates were negligible for all configurations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of left atrial dilatation on the endocardial atrial defibrillation threshold: a study in an ovine model of pacing induced dilated cardiomyopathy

Left atrial (LA) dilation is a common finding in patients with chronic atrial fibrillation (AF). Progressive dilatation may alter the atrial defibrillation threshold (ADFT). In our study, epicardial electrodes were implanted on the LA free wall and right ventricular apex of eight adult sheep. Large surface area, coiled endocardial electrodes were positioned in the coronary sinus and right atrium (RA). LA dilatation was induced by rapid ventricular pacing (190 beats/min) for 6 weeks and echocardiographically assessed weekly along with the ADFT (under propofol anesthesia). LA effective refractory period (ERP) was measured every 2-3 days using a standard extra stimulus technique and 400 ms drive. The AF cycle length (AFCL) was assessed from LA electrograms. During the 6 weeks of pacing the mean LA area increased from 6.1 +/- 1.5 to 21.3 +/- 2.4 cm2. There were no significant changes in the mean ADFT (122 +/- 15 V), circuit impedance (46 +/- 5 omega), or LA AFCL (136 +/- 23 ms). There was a significant increase in the mean LA ERP (106 +/- 10 ms at day 0, and 120 +/- 13 ms at day 42 of pacing). In this study, using chronically implanted defibrillation leads, the minimal energy requirements for successful AF were not significantly altered by ongoing left atrial dilatation. This finding is a further endorsement of the efficiency of the coronary sinus/RA shock vector. Furthermore, the apparent stability of the AF present may be a further indication of a link between the type of AF and the ADFT.     

Effect of levodopa on the human dark adaptation threshold

BACKGROUND: In several species there is strong evidence that the retinal dopamine turnover is influenced by retinal dark and light adaptation. In the human retina, dopamine has been found in amacrine and interplexiform cells. METHODS: In the present study, the influence of orally administered levodopa on the human dark adaptation was investigated in healthy subjects using the Goldmann-Weekers adaptometer. To exclude effects of levodopa on the pupil size, a second group was examined after pupil dilation before each examination. A third and fourth group were examined under the same conditions as the first two groups, but without levodopa administration. RESULTS: Levodopa caused a uniform threshold elevation throughout dark adaptation with undilated and dilated pupils. No effect on sensitivity was observed in the control groups. CONCLUSION: These results show a dopaminergic reduction in sensitivity during human dark adaptation.     

Utilizing the C-terminal cleavage activity of a protein splicing element to purify recombinant proteins in a single chromatographic step

A conventional affinity protein purification system often requires a separate protease to separate the target protein from the affinity tag. This paper describes a unique protein purification system in which the target protein is fused to the C-terminus of a modified protein splicing element (intein). A small affinity tag is inserted in a loop region of the endonuclease domain of the intein to allow affinity purification. Specific mutations at the C-terminal splice junction of the intein allow controllable C-terminal peptide bond cleavage. The cleavage is triggered by addition of thiols such as dithiothreitol or free cysteine, resulting in elution of the target protein while the affinity-tagged intein remains immobilized on the affinity column. This system eliminates the need for a separate protease and allows purification of a target protein without the N-terminal methionine. We have constructed general cloning vectors and demonstrated single-column purification of several proteins. In addition, we discuss several factors that may affect the C-terminal peptide bond cleavage activity.     

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects

OBJECTIVES: To understand the pharmacokinetic and pharmacodynamic properties of recombinant human erythropoietin (epoetin alfa) and to continue to optimize dosing regimens by determining whether administration of single high doses of epoetin alfa is as effective as repeated administration. METHODS: Epoetin alfa was administered as single subcutaneous doses of 300, 450, 600, 900, 1200, 1350, 1800, and 2400 IU/kg and in multiple subcutaneous dose regimens: 150 IU/kg 3 times a week for 4 weeks and 600 IU/kg once per week for 4 weeks in 2 open-label, randomized placebo-controlled studies in healthy volunteers. RESULTS: The absorption rate of epoetin alfa after subcutaneous administration was independent of dose, whereas clearance was dose-dependent in that it decreased with increasing dose. There was a linear relationship between response measured as percentage of reticulocytes area under the curve (AUC) and erythropoietin AUC for single doses up to 1800 IU/kg. Beyond the 1800 IU/kg dose, there was a saturation of response. The mean percentage of reticulocytes after single-dose regimens began to increase by days 3 to 4, reached their maximum at days 8 to 11, and returned to baseline values by day 22. In contrast, the mean percentage of reticulocytes after both multiple-dose regimens were maintained above baseline values through day 22 as both regimens stimulated modest but sustained increases in percentage of reticulocytes (1% to 2%). The mean percentage of reticulocytes AUC for 600 IU/kg epoetin alfa given once a week for 4 weeks was apparently greater than the mean percentage of reticulocytes AUC for 150 IU/kg 3 times a week for 4 weeks. Although daily oral iron supplementation was given, mean serum ferritin levels declined by approximately 75% through day 22 in subjects treated with multiple doses of epoetin alfa. CONCLUSIONS: These findings show that the pharmacologic response to epoetin alfa is a function of dose and dosing regimen. Repeated administration of epoetin alfa was more effective in stimulating a reticulocyte response than single-dose administration of the same total amount of epoetin alfa.     

Effect of calcaneal osteotomy and plantar fasciotomy on arch configuration in a flatfoot model

Expressed emotion is a robust and reliable predictor of psychiatric relapse across a range of psychopathological conditions and diagnoses. Theoretical speculation about the expressed emotion construct has suggested that high levels of criticism in relatives might be linked to attributions and beliefs about the patient's ability to control his or her symptoms or problem behaviors. Although there is some empirical support for this notion, no study to date has examined relatives' beliefs about their own abilities to control problem situations. This study compared high- and low-critical relatives of patients with schizophrenia on a measure of locus of control. Consistent with prediction, the locus of control scores of high-critical relatives were indicative of a more internal locus of control, whereas those of the low-critical relatives were indicative of a more external locus of control.