Biphasic Research Articles

Primary Localized Cutaneous Amyloidosis in Central Europe: A Retrospective Monocentric Study on Epidemiology and Therapy.

Amyloid deposits can be the cause of many chronic diseases. Primary localized cutaneous amyloidosis (PLCA) is a chronic dermatologic condition with amyloid deposits in the papillary dermis. The most common types of the keratinocyte-derived form of PLCA include macular (MA), lichen (LA), and biphasic (BA) amyloidosis. The estimated prevalence of PLCA in the Asian population is 0.98/10,000, which is higher than in the European population; thus, epidemiologic data on PLCA in the Caucasian population are limited. We performed a retrospective single-center study analyzing epidemiologic characteristics of a Central European PLCA population. Epidemiologic data regarding age, sex, skin phototype (Fitzpatrick scale I-VI), disease duration, comorbidities, history of atopy, and family history of PLCA were collected. Clinical characteristics, localization of PLCA lesions, applied therapies and treatment outcomes were also analyzed. Dermoscopic characteristics were also evaluated. A total of 41 patients diagnosed with PLCA were included, with 22 presenting with macular, 18 with lichen, and 1 with biphasic amyloidosis. The male/female ratio was 16/25, and mean age at diagnosis was 54.6 ± 15.2 years (range 27-87 years). The mean age at the onset of PLCA was 53 ± 16.1 years (range 19-79 years) in MA, 46.7 ± 18.2 years (range 14-73 years) in LA, and 26 years in BA. The interscapular region in MA and the extensor surface of the lower extremities in LA proved to be localization-related areas. In our center, a wide range of therapeutic options was applied, with the most prescribed being topical corticosteroids in all types of PLCA. We presented a retrospective, monocentric study on the epidemiology of PLCA in the Central European region. By examining the medical data of a significant number of PLCA patients, we compared our epidemiologic data with that of the Asian PLCA population. Due to the rarity of the condition, further randomized controlled trials and guidelines are needed to improve therapeutic outcomes.

LBSUN161 Relationship Of Shape Of Glucose OGTT Curves With Measures Of Cardiometabolic Health In African American Adolescents

Abstract Background and Aims Studies in youth and adults have shown that the shape of oral glucose tolerance test (OGTT) response curve may be a biomarker for insulin secretion and insulin sensitivity (IS). Individuals with monophasic (MPh) glucose response curve have lower IS and decreased beta-cell function compared to those with biphasic (BPh) pattern. The aim of this study was to assess if the shape of the glucose response curve of OGTT is associated with 2-D ECHO based indices of heart structure and function. Methods In a cross-sectional study, African American (AA) adolescents with and without obesity between the ages of 13-18 years were recruited to assess the relationship of blood pressure, obesity, and measures of cardiac health. Metabolic and inflammatory markers, 2-D ECHO and OGTT data were collected. The shape of the OGTT glucose response was classified based on a change from nadir to glucose-120 min of ≥ 4.5 mg/dL, and its association with cardiac health indices was calculated. R v.4.1.2 was used for analysis. Results Of the 276 individuals with available OGTT data (mean age 16.18 ± 1.70 years, 47.5% females), 39 (14.1%) had BPh curve. The individuals with BPh were lower in age (15.61 ± 1.68 vs 16.28 ± 1.68, p=0. 02), but similar in sex, BMI, BMIz and metabolic parameters. There was no difference in impaired glucose tolerance (27% [BPh] vs 15% [MPh], p=. 08). At 120 min, glucose (6.96 ± 0. 07 vs 6.31 ± 0. 07 mmol/L, p=. 05), and insulin (362.86 ± 13.69 vs 276.48 ± 13.61 uIU/mL, p=. 04) levels were higher in BPh. The glucose area under the curve (AUC) was lower in individuals with BPh (13.2 ± 1.23 vs 14.7 ± 1.16 mmol/L/hr, p <. 001) while the insulinogenic index (1.5 ± 3.79 vs 1.17 ± 2.74, p =. 03) and oral glucose disposition index were higher in both univariate analyses and after adjusting for age, sex and BMIz. The aortic root size was associated with the shape of the curve adjusting for age, sex and BMIz (p=. 03), but not ventricular or atrial mass, systolic or diastolic function. Conclusions There was lower proportion of individuals with BPh in this cohort of AA adolescents compared to published studies. Individuals with BPh had healthier beta-cell function indices. No significant relationship of the shape of the OGTT curve was seen with the metrics of heart structure or function at this age. Replication of results in adult cohort(s) is ongoing. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Monophasic versus biphasic hyaluronic acid filler for correcting nasolabial folds: a systematic review and meta-analysis.

Hyaluronic acid (HA) fillers are the most popular dermal fillers for wrinkle correction and facial rejuvenation. Recently, there has been an interest toward classifying HA fillers based on the cross-linking properties into monophasic (MHA) and biphasic (BHA) fillers. We aimed to compare the efficacy and safety outcomes between MHA and BHA fillers for the correction of nasolabial folds (NLFs). We searched Medline, Embase, and CENTRAL for randomized controlled trials (RCTs) that compared MHA filler to BHA filler for individuals with moderate-to-severe bilateral NLFs. We sought to evaluate the following outcomes: Wrinkle severity rating scale (WSRS), pain on visual analog scale (VAS), global aesthetic improvement scale (GAIS), and adverse events. The standardized mean difference (SMD) was used to represent continuous outcomes while risk ratio (RR) was used to represent dichotomous outcomes. A total of 11 RCTs that enrolled 935 participants deemed eligible. MHA filler revealed a significant improvement in the overall WSRS score and GAIS score compared to BHA filler (SMD=-0.38, 95% CI -0.49 to -0.27 and SMD=0.34, 95% CI 0.24-0.45, respectively). No significant difference was noted between MHA and BHA fillers in terms of pain score or adverse events (SMD=-0.39, 95% CI -0.81-0.03 and RR=1.00, 95% CI 0.89-1.12, respectively). MHA filler showed discernable cosmetic results and comparable effective and tolerability to BHA filler.

60-OR: OGTT Glucose Response Curves (GRC), Insulin Sensitivity (IS), and ß-Cell Function (ßCF) in RISE: Youth–Adult Contrast at Randomization and in Response to Interventions to Preserve ßCF

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p<0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p<0.005), but not IIn. Following intervention, the change in OGTT-GRC did not differ significantly between youth and adults (improvement: 14.5% vs. 18.0%, worsening 21.0% vs. 17.3%, no change 64.5% vs. 64.6% respectively). Moreover, there was no impact of M or G-M treatment on the change in OGTT-GRC from randomization to M12 in youth and adults. In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape. Disclosure S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

An Atmosphere-Breathing Refillable Biphasic Device for Cell Replacement Therapy.

Cell replacement therapy is emerging as a promising treatment platform for many endocrine disorders and hormone deficiency diseases. The survival of cells within delivery devices is, however, often limited due to low oxygen levels in common transplantation sites. Additionally, replacing implanted devices at the end of the graft lifetime is often unfeasible and, where possible, generally requires invasive surgical procedures. Here, the design and testing of a modular transcutaneous biphasic (BP) cell delivery device that provides enhanced and unlimited oxygen supply by direct contact with the atmosphere is presented. Critically, the cell delivery unit is demountable from the fixed components of the device, allowing for surgery-free refilling of the therapeutic cells. Mass transfer studies show significantly improved performance of the BP device in comparison to subcutaneous controls. The device is also tested for islet encapsulation in an immunocompetent diabetes rodent model. Robust cell survival and diabetes correction is observed following a rat-to-mouse xenograft. Lastly, nonsurgical cell refilling is demonstrated in dogs. These studies show the feasibility of this novel device for cell replacement therapies.

Mono- and Bi-Phasic Cellulose Acetate Micro-Vectors for Anti-Inflammatory Drug Delivery.

In recent years, different processing technologies have been engineered to fabricate capsules or particles with peculiar properties (e.g., swelling, pH-sensitive response) at the micro and sub-micrometric size scale, to be used as carriers for controlled drug and molecular release. Herein, the development of cellulose acetate (CA) micro-carriers with mono- (MC) or bi-phasic (BC) composition is proposed, fabricated via electrohydrodynamic atomization (EHDA)—an electro-dropping technology able to micro-size polymer solution by the application of high voltage electrostatic forces. Image analysis allows identification of the process parameters to optimize morphology, in terms of size distribution and shape. Meanwhile, an accurate rheological study has enabled investigating the interface between CA solutions with different viscosities to optimize BC systems. Release tests have confirmed that BC carriers can retain the drug more efficiently in acidic conditions, also providing a more gradual and sustained release until six days, with respect to MC carriers. Hence, all these results have proven that biphasic architecture significantly improves the capability of CA microcarriers to release ketoprofen lysinate, thus suggesting a new route to design core/shell systems for the retarded oral administration of anti-inflammatory drugs.

Stimulation Pattern Efficiency in Percutaneous Auricular Vagus Nerve Stimulation: Experimental Versus Numerical Data.

Percutaneous electrical stimulation of the auricular vagus nerve (pVNS) is an electroceutical technology. The selection of stimulation patterns is empirical, which may lead to under-stimulation or over-stimulation. The objective is to assess the efficiency of different stimulation patterns with respect to individual perception and to compare it with numerical data based on in-silico ear models. Monophasic (MS), biphasic (BS) and triphasic stimulation (TS) patterns were tested in volunteers. Different clinically-relevant perception levels were assessed. In-silico models of the human ear were created with embedded fibers and vessels to assess different excitation levels. TS indicates experimental superiority over BS which is superior to MS while reaching different perception levels. TS requires about 57% and 35% of BS and MS magnitude, respectively, to reach the comfortable perception. Experimental thresholds decrease from non-bursted to bursted stimulation. Numerical results indicate a slight superiority of BS and TS over MS while reaching different excitation levels, whereas the burst length has no influence. TS yields the highest number of asynchronous action impulses per stimulation symbol for the used tripolar electrode set-up. The comparison of experimental and numerical data favors the novel TS pattern. The analysis separates excitatory pVNS effects in the auricular periphery, as accounted by in-silico data, from the combination of peripheral and central pVNS effects in the brain, as accounted by experimental data. The proposed approach moves from an empirical selection of stimulation patterns towards efficient and optimized pVNS settings.

The efficacy and safety of external biphasic defibrillation in toy breed dogs

AbstractObjective: To evaluate the efficacy and safety of biphasic (BP) defibrillation in toy breed dogs (<5 kg of body weight).Design: Prospective, clinical experimental study.Setting: Veterinary teaching hospital.Animals: Five dogs (pilot study) and 10 dogs (comparison study of biphasic versus monophasic defibrillation).Measurements and main results: The efficacy of defibrillation was compared by estimating E80 (80% probability of successful defibrillation) after biphasic (BP) and monophasic (MP) defibrillations. The E80 for BP defibrillation was 7.24±1.33 J (2.24±0.41 J/kg) and 10.24±1.34 J (3.18±0.12 J/kg) for MP defibrillation. BP waveform required 30% less shock energy for a successful defibrillation. In order to compare the safety of defibrillation, we evaluated changes in cardiac biomarkers, electrocardiogram, echocardiographical left ventricular index, and aortic pressure during and after BP and MP defibrillation. All dogs treated by either BP or MP defibrillation survived. Pulseless electrical activity occurred in 2 of 5 dogs during MP defibrillation. The levels of cardiac biomarkers were elevated and sustained for longer periods in the MP defibrillation group. Electrocardiographic changes (e.g., QT prolongation, the time to return to an isoelectric ST segment after shocks) were more severe and longer in the MP defibrillation group. In addition, overall left ventricular cardiac performance was severely depressed in the MP group compared with the BP group.Conclusion: Our findings suggest that BP defibrillation is more effective and safer than MP defibrillation. We determined the acceptable shock energy to be 2–4 J/kg for toy breed dogs.

Alternative pulse shapes in electrical hearing

Cochlear implants (CIs) stimulate the auditory nerve with trains of symmetric biphasic (BI) pulses. We review studies showing that more efficient stimulation can be achieved by modifying these pulses by (1) increasing the inter-phase gap (IPG) between the two phases of each pulse, thereby delaying the recovery of charge, (2) increasing the duration and decreasing the amplitude of one phase - so-called "pseudomonophasic (PS)" waveforms, and (3) combining the pseudomonophasic stimulus with an IPG in a "delayed pseudomonophasic" waveform (PS_IPG). These efficiency gains, measured using changes in threshold and loudness, occur at a wide range of pulse rates, including those commonly used in current CI systems. In monopolar mode, dynamic ranges are larger for PS and for long-IPG pulse shapes than for BI pulses, but this increase in DR is not accompanied by a higher number of discriminable loudness steps, and hence, in a better coding of loudness. Moreover, waveforms with relatively short and long interphase gaps do not yield different patterns of excitation despite the relatively large differences in threshold. Two important findings are that, contrary to data obtained in animal experiments, anodic currents are more effective than cathodic stimulation for human CI patients and that the thresholds decrease with increases in IPG over a much longer time course (more than 3 ms) than for animals. In this review it is discussed how these alternative pulse shapes may be beneficial in terms of reducing power consumption and channel interactions, which issues remain to be addressed, and how models contribute to guiding our research.

Tunnel Propagation of Postshock Activations as a Hypothesis for Fibrillation Induction and Isoelectric Window

Comprehensive understanding of the ventricular response to shocks is the approach most likely to succeed in reducing defibrillation threshold. We propose a new theory of shock-induced arrhythmogenesis that unifies all known aspects of the response of the heart to monophasic (MS) and biphasic (BS) shocks. The central hypothesis is that submerged "tunnel" propagation of postshock activations through shock-induced intramural excitable areas underlies fibrillation induction and the existence of isoelectric window. We conducted simulations of fibrillation induction using a realistic bidomain model of rabbit ventricles. Following pacing, MS and BS of various strengths/timings were delivered. The results demonstrated that, during the isoelectric window, an activation originated deep within the ventricular wall, arising from virtual electrodes; it then propagated fully intramurally through an excitable tunnel induced by the shock, until it emerged onto the epicardium, becoming the earliest-propagated postshock activation. Differences in shock outcomes for MS and BS were found to stem from the narrower BS intramural postshock excitable area, often resulting in conduction block, and the difference in the mechanisms of origin of the postshock activations, namely intramural virtual electrode-induced phase singularity for MS and virtual electrode-induced propagated graded response for BS. This study provides a novel analysis of the 3D mechanisms underlying the origin of postshock activations in the process of fibrillation induction by MS and BS and the existence of isoelectric window. The tunnel propagation hypothesis could open a new avenue for interventions exploration to achieve significantly lower defibrillation threshold.

Serum cardiac markers response to biphasic and monophasic electrical cardioversion for supraventricular tachyarrhythmia—a randomised study

Electrical cardioversion in patients with various types of supraventricular tachyarrhythmia (SVT) may induce serum cardiac markers elevation. Only a few studies have evaluated the impact of the type of shock waveform on electrical myocardial injury. The aim of our study was to compare the response of serum cardiac markers to biphasic and monophasic cardioversion for SVT. One hundred and forty one patients with various SVTs referred for electrical cardioversion were randomised to monophasic (MP) or biphasic (BP) cardioversion. Serum levels of creatine kinase (CK), MB fraction of CK (CK-MB), myoglobin and troponin I were analysed before cardioversion and 254+/-58 min after the procedure. Average age of the patients was 67.9+/-11.3 years, 71 underwent BP and 70 MP cardioversion. In MP group, cumulative energy (CE)>150J was associated with significant elevation of CK and myoglobin levels after cardioversion (1.52+/-3.81 microkat/l and 187+/-433 microg/l), while CE<150J was not (-0.04+/-0.34 and 4+/-11, p<0.05). In BP group, CE>150J was associated with significant but smaller CK elevation (0.27+/-1.09 microkat/l, p<0.05) and comparable myoglobin elevation (80.7+/-21.4 microg/l, p<0.05). CE>150J was the only independent positive predictor for CK and myoglobin elevation in both groups. No significant changes in CK-MB and Troponin I levels after cardioversion were identified. According to our study, electrical cardioversion for SVTs is not associated with biochemical signs of myocardial injury. Application of CE>150J can be followed by CK and myoglobin elevation most likely due to skeletal muscle damage. This reaction is more pronounced in MP than in BP cardioversion.

Asymmetric Pulses in Cochlear Implants: Effects of Pulse Shape, Polarity, and Rate

Existing cochlear implants stimulate the auditory nerve with trains of symmetric biphasic (BP) pulses. Recent data have shown that modifying the pulse shape, while maintaining charge balance, may be beneficial in terms of reducing power consumption, increasing dynamic range, and limiting channel interactions. We measured thresholds and most comfortable levels (MCLs) for various 99-pulses-per-second (pps) stimuli. "Pseudomonophasic (PS)" pulses consist of a brief phase of one polarity followed immediately by a longer and lower-amplitude phase of the opposite polarity. We focused on a novel variant of PS pulses, termed the "delayed pseudomonophasic (DPS)" stimulus, in which the longer phase is presented midway between the short phases of two consecutive pulses. DPS pulse trains produced thresholds that were more than 10 dB lower than those obtained with BP pulses. This reduction was much greater than the 0- to 3-dB drop obtained with PS pulses and was still more than 6 dB when a pulse rate of 892 pps was used. A study of the relative contributions of the two phases of DPS suggested that the short, high-amplitude phase dominated the perceived loudness. This study showed major threshold and MCL reductions using a DPS stimulus compared to the widely used BP stimulus. These reductions, which were predicted by a simple linear filter model, might lead to considerable power savings if implemented in a cochlear implant speech processor.

Interactions between CPR and defibrillation waveforms: effect on resumption of a perfusing rhythm after defibrillation

Background: Cardiopulmonary resuscitation (CPR) improves survival from cardiac arrest. The interactions between CPR and the new biphasic (BiP) defibrillation waveforms have not been defined. Our purpose was to compare the effect of CPR versus no CPR during BiP and damped sinusoidal (DS) shocks on the termination of ventricular fibrillation (VF) and the resumption of a perfusing rhythm. Methods: We studied 20 pigs; VF was induced electrically and allowed to persist for 6 min. During VF episodes each pig received (in random order): (a) 6 min of full CPR (continuous ventilation and closed chest mechanical compression (Thumper, Michigan Instruments)) followed by DS defibrillation at 100 J; (b) no CPR, DS defibrillation; (c) 6 min of full CPR and BiP defibrillation at 100 J; and (d) no CPR, BiP defibrillation. Results: BiP shocks with CPR terminated VF in 83% of attempts versus 45% without CPR (15/18 and 5/11 respectively, P<0.05). DS shocks with CPR were successful in terminating VF in 53% of attempts; DS shocks without CPR were successful in 44% (8/15 and 7/16, respectively, P=NS). No animal achieved a perfusing rhythm after shocks of either waveform if CPR did not precede the shocks during the 6-min VF period, whereas if CPR was administered during VF 46% (11/24) of the combined BiP/DS shocks restored a perfusing rhythm ( P<0.01). Conclusion: In this experimental long duration VF model, CPR was essential for a perfusing rhythm after termination of VF by shocks with either waveform. CPR facilitated the termination of VF and resumption of a perfusing rhythm after biphasic waveform defibrillation but not after damped sinusoidal waveform defibrillation.

Modeling the interaction between propagating cardiac waves and monophasic and biphasic field stimuli: the importance of the induced spatial excitatory response.

Biphasic (BP) defibrillation waveforms have been shown to be significantly more efficacious than equivalent monophasic (MP) waveforms. However, when defibrillation fails, it tends to do so first in distal regions of the heart where induced field gradient magnitudes are lowest. We tested the hypothesis that the improved efficacy of BP waveforms results from their enhanced ability to prevent the initiation of new postshock activation fronts behind preexisting wavetails, rather than from any significantly improved ability to terminate preexisting wavefronts. An idealized computer model of a one-dimensional cardiac strand was used to investigate the spatial and temporal interactions between an underlying propagation front (or tail) and uniform MP or BP field stimuli of various intensities. Axial discontinuities from intercellular junctions induced sawtooth patterns of polarization during such field stimuli, enabling the shocks to interact directly with all cells. MP and BP diastolic thresholds were essentially equal. All suprathreshold MP and BP field stimuli successfully terminated preexisting wavefronts by directly depolarizing tissue ahead of those fronts, thus blocking their continued progression. However, the postshock response at the wavetail was significantly dependent on the shape and strength of the administered field. Low-strength MP stimuli induced an all-or-none excitation response across the wavetail, producing a sharp spatial transmembrane voltage gradient from which a new sustained anterogradely propagating wavefront was initiated. In contrast, low-strength BP field stimuli induced a spatially graded excitatory response whose voltage gradient was insufficient to initiate such a wavefront. Higher-strength MP and BP stimuli both produced graded excitatory responses with no subsequent propagation. Shock-induced spatial "all-or-none" excitatory responses facilitate, and graded excitatory responses prevent, the postshock initiation of new propagating wavefronts. Moreover, BP field stimuli can induce such graded excitatory responses at significantly lower stimulus strengths than otherwise equivalent MP stimuli. Therefore, these results support an alternative "graded excitatory response" mechanism for the improved efficacy of BP over MP field stimuli in low gradient regions.

714-6 Increased Action Potential Prolongation by Low Voltage Biphasic versus Monophasic Field Stimuli

In an in-vitro model for defibrillation, we compared action potential prolongation (APP) by monophasic (MONO) and biphasic (BI) field stimulus shocks in epicardial tissue strips from 10 dogs. Strips were paced at one end while cellular impalements were maintained in the center (cell A) to measure APP and at the other end (cell B) to determine if shocks produced propagated activations. Rectangular shocks (0.5 to 10 V/cm) were delivered with MONO (8 ms) or BI (4.8/3.2 ms) waveforms at times ranging from 44% to 112% of the APD90 of cell A. Recordings were made during 3975 shocked and 2578 control action potentials. APP was the % increase in shocked repolarization time relative to the interlaced controls. While weaker MONO and BI shocks produced propagated activations, the threshold intensity ABOVE which shocks did NOT produce activations was 25.9% lower (p &lt; 0.0005) for BI (2.78 V/cm) versus MONO (3.75 V/cm). At most intensities and timings, MONO produced more APP than BI. However, for 2 to 4 V/cm shocks at 90% to 100% of APD90, BI produced more APP than MONO (36.9% versus 17.7%, P &lt; 0.0001) shocks. Thus, increased defibrillation efficacy of BI waveforms may result from a greater APP by BI in the low-voltage gradient regions of the heart during defibrillation.

Cardiac responses to premature monophasic and biphasic field stimuli: Results from cell and tissue modeling studies

Experimental and clinical observations confirm that certain biphasic (BP) defibrillation shocks are significantly more efficacious than equivalent monophasic (MP) shocks, yet the mechanisms underlying these improvements are still not well understood. The authors used two separate, but related, computer models to investigate in detail the excitation responses of active cardiac cells and tissue to idealized premature extracellular MP and BP field stimuli. The results revealed a large disparity in MP and BP excitation responses to low-strength, but not high-strength, fields. In particular, at these low-strength levels, the polarity reversal within BP shocks effectively extends excitability to earlier cellular refractory states than can be achieved with simple MP shocks. Moreover, whereas low-strength MP shocks induce a distinct all-or-none excitatory response to varying shock prematurities, the excitatory response to equivalent BP shocks remains highly graded. In tissue simulations where such field stimuli intersected propagating wave fronts, the all-or-none excitatory response elicited by low-strength MP shocks created a postshock discontinuity in the spatial transmembrane voltage profile, which initiated a new propagation wave front. In contrast, the graded excitatory response elicited by BP waveforms effectively prevented the formation of postshock wave fronts. High-strength MP and BP stimuli prevented renewed propagation equally well. In conclusion, these results suggest a new mechanism for BP defibrillation superiority over MP waveforms: that the graded excitatory response to BP stimuli at low-field strengths effectively prevents the formation of large spatial transmembrane voltage gradients, which can lead to renewal of propagated wave fronts

The impact of converting to a biphasic blood-culture system on the overall cost and the incidence of pseudobacteremia

After converting from a conventional broth (CB) system to a biphasic (BP) agar-slide blood-culture system (Septi-Chek), our laboratory noted an increase in positive blood cultures in general, and in coagulase-negative staphylococci (CNS) in particular. To investigate these findings, we compared all blood cultures collected over a 21-month period using CB and then BP systems, totaling 28,199 blood cultures. The frequency of positive blood cultures increased from 9.2% to 12.7% ( p < 0.0001), whereas CNS isolation increased from 2.6% to 5.2% ( p < 0.0001). There was no significant change in the incidence of true primary or secondary bacteremia due to CNS ( p = 0.9). The isolation of other pathogens, including Staphy-lococcus aureus, Candida albicans, Bacteroides species, and Gram-negative bacilli increased from 6.5% to 7.1% ( p < 0.05). We estimated the cost of processing 28,000 blood cultures by both CB and BP systems, using positivity rates of 9.2% and 12.7%, respectively, and standards provided by the College of American Pathologists (CAP, 1991) for workload hours of technologist time. We calculated a higher overall cost for the BP system. However, the use of this system eliminated the use of needles and syringes for subculture of bottles showing no growth, thus decreasing the risk of technologist exposure to body fluids. Despite the increased cost and more frequent occurrence of pseudobacteremia, the enhanced sensitivity and increased safety of the BP system justified its use in the prompt identification of patients with true bacteremia.