Evaluation of the operating internal resistance, inductance, and capacitance of intact damped sine wave defibrillators

A method is developed for determining actual values of circuit elements in a damped sine wave (Lown waveform) defibrillator, solely from measurements of the output, using two or more power resistors and a storage oscilloscope. If a defibrillator containing capacitance, C, inductance, L, and internal resistance, Ri, is discharged into increasing 5- to 100-ohm resistive loads, R, it is shown for underdamped output waveforms that aˆ = Ri/2L + R/2L and cˆ = CRi + CR, where aˆ = /[t2 tan(t1/t2)], cˆ = 2 aˆ /[ 2 aˆ + (/t2)2], t1 = time from onset to peak, and t2 = time from onset to first zero crossing of the output waveform on the oscilloscope trace. Linear plots of aˆ vs. R are constructed for seven defibrillators, and values of Ri and L computed as intercept/slope and 1/(2 slope) respectively. C is given by the slope of a linear plot of cˆ vs. R. Delivered energy is accurately predicted as stored energy R/(Ri + R)

Temporal Stability and Precision of Ventricular Defibrillation Threshold Data

Over two-hundred measurements of the minimum damped sinusoidal current and energy for transchest electrical ventricular defibrillation (ventricular defibrillation threshold) were made to determine the stability and precision of threshold data in 15 pentobarbital-anesthetized dogs. Threshold was determined by repeated trials of fibrillation and defibrillation with successive shocks of diminishing current, each 19% less than that of the preceeding shock. The lowest shock intensity that defibrillated was defined as threshold. In three groups of five dogs each, threshold was measured at intervals of 60, 15, and 5 min. over periods of 8, 5, and 1 hr. respectively. Similar results were obtained for all groups. There was no significant change in mean threshold current with time. Due to a decrease in transchest impedance, threshold delivered energy decreased by 10% during the first hour of testing. The standard deviations for threshold peak current and delivered energy in a given animal were 11 and 22 percent of their respective mean values. Arterial blood pH, pc02, and p02 averaged 7.38, 34 mmHg, and 72 mmHg respectively. The rates of change of pH, pCO2 and p02 were not significantly different from zero. The data demonstrate that ventricular defibrillation threshold is a stable physiologic parameter which may be measured with reasonable precision

Dependence of Defibrillation Threshold Upon Extracellular/Intracellular K+ Concentrations

The effect of increasing extracellular potassium concentration (Ko) upon electrical ventricular defibrillation threshold was investigated in pentobarbital anesthetized dogs treated with intravenous potassium chloride. Defibrillation threshold fell during potassium intoxication. The percent decrease in defibrillation threshold was linearly related to the logarithm of Ko and to the potassium equilibrium potential, EK, calculated from measured extracellular and intracellular potassium concentrations of ventricular muscle. In dogs supported by left ventricular bypass in order to maintain the circulation during potassium intoxication, the values of Ko and EK required for spontaneous, K+ induced defibrillation (electrical defibrillation threshold = zero) were 16.6 mEq/L and -46 mV compared to the normal values of 3.9 mEq/L and -84 mV. Changes in defibrillation threshold related to changes in EK may be significant events in digitalis intoxication and in myocardial anoxia during prolonged fibrillation. Defibrillation of the heart is often discussed as a large scale analog of cardiac pacing. Termination of atrial or ventricular fibrillation by a strong electric shock, applied with paddle electrodes across the chest or directly to the heart, is assumed to be the result of stimulation of a diffuse mass of potentially excitable cells (1, 2). The mechanism of defibrillation is usually stated to be the consequent production of a simultaneously refractory state in the entirety of a critical mass of the fibrillating myocardium (3, 4)

Elevation of ventricular defibrillation threshold in dogs by antiarrhythmic drugs

Effects of antiarrhythmic drugs upon the threshold delivered energy (TDE) and threshold peak current (TPC) for electrical ventricular defibrillation by damped sinusoidal shocks were investigated in 25 pentobarbital-anesthetized dogs. TDE and TPC were increased by the three antiarrhythmic drugs tested. Bolus injections produced a transient rise, and continuous infusions produced a steady rise in defibrillation threshold. The maximal percent elevations in mean defibrillation threshold during the 60 minutes after intravenous drug treatment in groups of n = 5 dogs were: Treatment % increase in TDE % increase in TPC Lidocaine bolus (3 mg/kg) 48 26 Lidocaine (0.5 mg/Kg/min) 99 45 Quinidine bolus (50 mg/Kg) 172 70 Diphenylhydantoin (1 mg/Kg/min) 83 35 Controls 1 4 Accordingly, individuals receiving antiarrhythmic drugs whose hearts nonetheless fibrillate may require greater electric shock strength for defibrillation

Intravenous Polyethylene Glycol Inhibits the Loss of Cerebral Cells after Brain Injury

We have tested the effectiveness of polyethylene glycol (PEG) to restore the integrity of neuronal membranes after mechanical damage secondary to severe traumatic brain injury (TBI) produced by a standardized head injury model in rats. We provide additional detail on the standardization of this model, particularly the use and storage of foam bedding that serves to both support the animal during the impact procedure and to dampen the acceleration of the brass weight. Further, we employed a dye exclusion technique using ethidium bromide (EB; quantitative evaluation) and horseradish peroxidase (HRP; qualitative evaluation). Both have been successfully used previously to evaluate neural injury in the spinal cord since they enter cells when their plasma membranes are damaged. We quantified EB labeling (90 M in 110 L of sterile saline) after injection into the left lateral ventricle of the rat brain 2 h after injury. At six h after injection and 8 h after injury, the animals were sacrificed and the brains were analyzed. In the injured rat brain, EB entered cells lining and medial to the ventricles, particularly the axons of the corpus callosum. There was minimal EB labeling in uninjured control brains, limited to cells lining the luminal surfaces of the ventricles. Intravenous injections of PEG (1 cc of saline, 30% by volume, 2000 MW) immediately after severe TBI resulted in significantly decreased EB uptake compared with injured control animals. A similar result was achieved using the larger marker, HRP. PEG-treated brains closely resembled those of uninjured animals

Theoretical Feasibility of Vasodilator-enhanced Local Tumor Heating

Normal arterioles, in contrast to the abnormal microvasculature of many solid tumors, provide a target for selective drug action that can enhance local heat treatment of the tumors. Measurements of tissue blood flow with radioactive microspheres and estimates of changes in blood flow with thermal clearance methods revealed that vasodilator drugs either decreased or did not alter blood flow in hamster melanoma, rat hepatoma, and canine transmissible venereal tumor, while increasing perfusion in adjacent normal tissues 2 to 4-fold. Solutions of the bio-heat transfer equation, which take into account such selective effects of vasodilators on blood flow in normal tissues, clearly demonstrate improved selective heating for spheroidal tumors over 2 cm in diameter. In the presence of vasodilator drug effect, steady-state center tumor temperatures of 45-50°C can be achieved by increased power input, while surrounding normal tissues remain below 42°C

Duplication of the EFNB1 Gene in Familial Hypertelorism: Imbalance in Ephrin-B1 Expression and Abnormal Phenotypes in Humans and Mice

Familial hypertelorism, characterized by widely spaced eyes, classically shows autosomal dominant inheritance (Teebi type), but some pedigrees are compatible with X-linkage. No mechanism has been described previously, but clinical similarity has been noted to craniofrontonasal syndrome (CFNS), which is caused by mutations in the X-linked EFNB1 gene. Here we report a family in which females in three generations presented with hypertelorism, but lacked either craniosynostosis or a grooved nasal tip, excluding CFNS. DNA sequencing of EFNB1 was normal, but further analysis revealed a duplication of 937 kb including EFNB1 and two flanking genes: PJA1 and STARD8. We found that the X chromosome bearing the duplication produces ∼1.6-fold more EFNB1 transcript than the normal X chromosome and propose that, in the context of X-inactivation, this difference in expression level of EFNB1 results in abnormal cell sorting leading to hypertelorism. To support this hypothesis, we provide evidence from a mouse model carrying a targeted human EFNB1 cDNA, that abnormal cell sorting occurs in the cranial region. Hence, we propose that X-linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin-B1 (as well as simple presence/absence) leads to craniofacial abnormalities. Hum Mutat 32:1–9, 2011. © 2011 Wiley-Liss, Inc

Lookback option pricing using the Fourier transform B-spline method

We derive a new, efficient closed-form formula approximating the price of discrete lookback options, whose underlying asset price is driven by an exponential semimartingale process, which includes (jump) diffusions, Lévy models, affine processes and other models. The derivation of our pricing formula is based on inverting the Fourier transform using B-spline approximation theory. We give an error bound for our formula and establish its fast rate of convergence to the true price. Our method provides lookback option prices across the quantum of strike prices with greater efficiency than for a single strike price under existing methods. We provide an alternative proof to the Spitzer formula for the characteristic function of the maximum of a discretely observed stochastic process, which yields a numerically efficient algorithm based on convolutions. This is an important result which could have a wide range of applications in which the Spitzer formula is utilized. We illustrate the numerical efficiency of our algorithm by applying it in pricing fixed and floating discrete lookback options under Brownian motion, jump diffusion models, and the variance gamma process