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Pressure volume parameters for optimal function of an intraaortic balloon without a pump.

An air filled intraaortic balloon connected to an extravascular air chamber (compression chamber system-CCS) was used in 10 anesthetized dogs to increase its stroke volume (SV). Highest SV increases (up to over 200%) were observed at low SV states, with a high CCS volume and with high increases of the systolic pressure. The CCS pressure--systolic pressure relationship was a sigmoid-like curve. In conclusion, highest SV's may be achieved at low SV states, using CCS volumes about 400 ml and the highest CCS pressure that may cause a linear aortic pressure increase.

Animals

Optimization of a polypyrrole glucose oxidase biosensor.

An amperometric glucose biosensor was fabricated by the electrochemical polymerization of pyrrole onto a platinum electrode in the presence of the enzyme glucose oxidase in a KCl solution at a potential of +0.65 V versus SCE. The enzyme was entrapped into the polypyrrole film during the electropolymerization process. Glucose responses were measured by potentiostating the enzyme electrode at a potential of +0.7 V versus SCE in order to oxidize the hydrogen generated by the oxidation of glucose by the enzyme in the presence of oxygen. Experiments were performed to determine the optimal conditions of the polypyrrole glucose oxidase film preparation (pyrrole and glucose oxidase concentrations in the plating solution) and the response to glucose from such electrodes was evaluated as a function of film thickness, pH and temperature. It was found that a concentration of 0.3 M pyrrole in the presence of 65 U/ml of glucose oxidase in 0.01 M KCl were the optimal parameters for the fabrication of the biosensor. The optimal response was obtained for a film thickness of 0.17 microns (75 mC/cm2) at pH 6 and at a temperature of 313 K. The temperature dependence of the amperometric response indicated an activation energy of 41 kJ/mole. The linearity of the enzyme electrode response ranged from 1.0 mM to 7.5 mM glucose and kinetic parameters determined for the optimized biosensors were 33.4 mM for the Km and 7.2 microA for the Imax. It was demonstrated that the internal diffusion of hydrogen peroxide through the polypyrrole layer to the platinum surface was the main limiting factor controlling the magnitude of the response of the biosensor to glucose. The response was directly related to the enzyme loading in the polypyrrole film. The shelf life and the operational stability of the optimized biosensor exceed 500 days and 175 assays, respectively. The substrate specificity of the entrapped glucose oxidase was not altered by the immobilization procedure.

Biosensing Techniques

Application of modified Rosenbrock's method for optimization of nutrient media used in microorganism culturing.

The Rosenbrock's procedure has been modified for optimization of nutrient medium composition and has been found to be less tedious than the Box-Wilson method, especially for larger numbers of optimized parameters. Its merits are particularly obvious with multiparameter optimization where the gradient method, so far the only one employed in microbiology from a variety of optimization methods (e.g., refs, 9 and 10), becomes impractical because of the excessive number of experiments required. The method suggested is also more stable during optimization than the gradient methods which are very sensitive to the selection of steps in the direction of the gradient and may thus easily shoot out of the optimized region. It is also anticipated that other direct search methods, particularly simplex design, may be easily adapted for optimization of medium composition. It is obvious that direct search methods may find an application in process improvement in antibiotic and related industries.

Culture Media

The evolution strategy--a search strategy used in individual optimization of electrical parameters for therapeutic carotid sinus nerve stimulation.

Optimization problems, arising in the search for parameters and/or techniques of functional electrostimulation (FES), disproportionally increase when multiple electrodes, electrode configurations, electrical parameters, and stimulation modes may be applied. When computational or investigational effort precludes systematic studies in FES, we propose to apply and evaluate Rechenberg's evolution strategy, which in technical use and numerical optimization has been valid in comparison to more traditional methods. This strategy implements mutation and selection processes in analogy to biological evolution. The effect of combined multiple input variables on a quality function (Q) is experimentally evaluated. The actual computed value of Q serves as a selection criterion for those input variable combinations which lead Q to approach a target value (maximization), similar to a hill-climbing procedure. In radiofrequency controlled, therapeutic electrical carotid sinus nerve stimulation (CSNS), we varied (mutated) combinations of pulse frequency and pulse amplitude parameters, according to the evolution strategy, in individual patients. CSNS lowers blood pressure and decreases heart rate. Q was computed from blood pressure and heart rate responses to CSNS. The strategy individually optimized electrical parameters to achieve large depressor responses upon CSNS. Although, in contrast to technical usage, only two input variables were investigated, and biomedical experience with the evolution strategy is limited so far, its potential use in other fields of FES, especially when more input variables are to be optimized, is discussed and encouraged.

Algorithms

[The dynamic property of glucagon secretion in response to blood glucose--analysis with the aid of the control theory using an artificial endocrine pancreas].

The precise dynamic property of glucagon secretion in response to glucose concentration has not yet been elucidated, since in in vitro studies using pancreatic islets, the co-existence of pancreatic B cells modifies the mode of glucagon secretion, and in vivo studies, the exogenous insulin administration greatly affects pancreatic A cell function. In this study, to clarify the dynamic property of glucagon secretion in response to glucose concentration and the ability of glucagon to raise hepatic glucose production, an artificial endocrine pancreas was employed as a research tool. Our originally developed artificial endocrine pancreas prepared the glucagon and/or glucose infusion algorithm as the counterregulatory system. The principle of glucagon and glucose infusion algorithm is set as the proportional plus derivative modes of action to blood glucose concentration with time delay constant, as follows; Gn.I.R.(t) = Gp[BGp - BG(t - tau)] + Gd[-delta BG(t - tau)] + Gc G.I.R.(t) = Cp[BGp - BG(t - tau)] + Cd[-delta BG(t - tau)] where Gn.I.R.(t) and G.I.R.(t) are glucagon infusion rate and glucose infusion rate, respectively. BGp is the projected value of blood glucose concentration, and BG(t) and delta BG are blood glucose concentrations and the rate of change in blood glucose concentration at time t respectively. Gp and Gd are coefficients for glucagon infusion, and Cp and Cd are those for glucose infusion. Gc is the constant for basal glucagon supplementation. tau(min) is the time delay constant for glucagon and glucose infusion. In a depancreatized dog, the blood glucose concentration was maintained at the normoglycemic level with intraportal insulin infusion using this artificial endocrine pancreas for at least one hour, then hypoglycemia was induced by iv bolus insulin injection (0.1 U/kg). Glucagon was infused intraportally or glucose was infused into the peripheral vein when the counterregulatory system was operated according to each of these algorithm by variously changing the parameters. In the intraportal glucagon infusion algorithm, with the optimal parameters based on proportional plus derivative modes of action with a 10-min time delay (Gp/Gd/Gc/tau = 0.2/0.4/0.6/10), both the blood glucose response curves and plasma glucagon profiles simulated those seen in normal dogs. On the other hand, glucagon infusion based only on the proportional action failed to simulate the blood glucose response and plasma glucagon profile of normal dogs. When glucose was infused on the basis of the proportional action with a 20-min time delay (Cp/Cd/tau - 0.2/0/20), the insulin-induced hypoglycemia in depancreatized dogs could be restored to normoglycemia in the sa

Animals

Single-tissue modeling of decompression schedules.

This paper deals with the development of a single-tissue model that simulates the uptake and elimination of inert gases by the body of a diver. The model utilizes an effective single tissue with different uptake and elimination time constants to account for the asymmetrical behavior of multiple-tissue human body models. The parameters of this effective tissue are selected according to an optimal strategy that minimizes safe deviation from the decompression requirements recommended by safe practice. The developed strategy is general in nature and can be readily applied to select the optimal parameters for a single-tissue model suitable for any dive regimen on air or mixed gas. As an illustration, the procedure is used to select the optimal tissue that best fits the Standard Air Decompression Tables recommended by the U.S. Navy. The results obtained are in close and safe agreement with the requirements of the U.S. Navy, and consistently fall in the range between the U.S. Navy and the Royal Navy tables.

Decompression

Studies on the feasibility of urinary bladder evacuation by direct spinal cord stimulation. I. Parameters of most effective stimulation.

In 30 female dogs, spinal cord stimulation was tested to find the optimal parameters producing good voiding and, hopefully, total bladder emptying. Twelve different electrodes or application modifications were examined. Variable frequencies, stimulus duration, and voltages were applied. Search of the site of highest detrusor response (micturition center) was easily identifiable. It became obvious that electrode design was not of critical importance: the responses were basically the same whether we used the wrap-around electrode, which stimulates an entire level, or the coaxial electrode which theoretically limits the current spread around its minute exposed tip. The stimulation parameters that gave the best results were: 2 to 5 volts; frequency: 10 to 15 cps; duration 1 msec. The site of highest detrusor response was round vertebral level L5 1/2, corresponding to cord level S2-4. Generally, no voiding was obtained because of too high sphincteric contraction during stimulation; it appeared that a sphincteric center overlaps the micturition center in either direction. To achieve successful voiding during stimulation, a separation of these two centers with selective stimulation of the detrusor center is necessary, eleiminating sphincteric contraction.

Animals

Long-term enhancement of CA1 synaptic transmission is due to increased quantal size, not quantal content.

Quantal components of Schaffer collateral synaptic transmission recorded intracellularly from CA1 pyramidal cells were examined using 2 methods: simultaneous recordings of CA3-CA1 cell-pairs, and minimal electrical stimulation in stratum radiatum. Quantal parameters estimated by the method of failures and by a computer algorithm that optimized parameter estimates using deconvolution of background noise were highly correlated. EPSP-amplitude histograms of CA3-CA1 cell pairs (N = 10) and minimal electrical stimulation (N = 33) could be adequately described either by Poisson or binomial statistics, or by both, and exhibited similar estimates of unit quantal size (q) and mean quantal content (m). Paired-pulse stimulation with 50 msec between stimuli resulted in an expected facilitation in the EPSP amplitude and increase in m during the second response, as estimated by noise deconvolution, by the decrease in apparent failures, and by a decrease in the coefficient of variation of the EPSP. Tetanization of the Schaffer collaterals that induced long-term enhancement (LTE/LTP) of the population response was associated with an average increase in q for minimal-stimulation responses, with no significant change in any estimate of m. Taken together, these data indicate that, under the present experimental conditions, LTE is expressed as an increase in quantal size, rather than an increase in the number of quanta released per presynaptic impulse. Although this is not definitive evidence for a postsynaptic mechanism, these findings do further restrict the classes of possible presynaptic mechanisms that may be proposed to account for LTE expression.

Action Potentials

The mechanism of reaction of ferricyanide-pretreated mixed-valence-state membrane-bound cytochrome oxidase with oxygen at 173 K.

1. The results of non-linear optimization studies on the mechanism of reaction of ferricyanide-pretreated mixed-valence-state cytochrome oxidase with O2 at 173 K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at four wavelength pairs (444-463 nm, 604-630 nm, 608-630 nm and 830-940 nm) and at two O2 concentrations (360 micron and 520 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, a random distribution of residuals and good determination of the optimized parameters, is a three-intermediate sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from optical wavelength scanning and e.p.r. spectroscopy obtained by low-temperature trapping studies, the possible valence states of the metal centres in each of the intermediates are discussed.

Chemical Phenomena

Feasibility of using intracardiac impedance measurements for capture detection.

Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.

Algorithms

[Electrostimulation of the phrenic nerve in dogs].

Respiratory parameters have been studied by electrical stimulation of phrenic nerves (EPN) in 12 dogs. The optimal parameters of an electrical stimulus were found for long-term EPN. EPN increased minute respiratory volume, when respiratory rate raised to 18 per min, and decreased, when respiratory rate diminished to 6 per min. Another parameter--oxygen utilization index--diminished at high respiratory rate and increased at low one, which reflected hyper- or hypoventilation status, respectively. The data obtained indicate that controlled lung ventilation may maintain living status of dogs for a long time without alteration of general respiratory parameters.

Animals

Systematic studies on parameters influencing the performance of the polymerase chain reaction.

To obtain a detailed understanding of the various factors influencing the polymerase chain reaction, we optimized parameters such as ion concentration, pH, primer sequence and concentration, hybridization stringency, cycle numbers, etc. Using 3 different plasmids (2 HIV2 clones and pUC18) and several genomic DNA samples from HIV-positive patients as templates, together with 6 sets of primers, the following optimal conditions were found: the DNA should be linearized, the primer concentration should be 0.1-0.2 mumol/l, and the magnesium ion concentration should be less than 2 mmol/l. The pH of the reaction mixture should be 8.5-9.0. Twenty five cycles are sufficient. For fragments greater than 10(3) bases the elongation time should be 5 min. The elongation temperature is not critical and can vary between 50 and 70 degrees C. The hybridization temperature can be used to control the specificity of the polymerase chain reaction and, finally, mismatches at the 3' end of the primer can totally inhibit the amplification.

Base Sequence

Electrical stimulation of the hypothalamus: new observations on the parameters necessary for ovulation in rats anaesthetised with pentobarbitone during the pro-oestrous "critical period".

The experiments were designed to specifiy optimal parameters of hypothalamic electrical stimulation to induce ovulation in rats anaesthetised with pentobarbitone during the "critical period" on the afternoon of pro-oestrous. We have established that duration of stimulation in the arcuate region of the hypothalamus is of greater importance than total number of pulses delivered. The minimum period of stimulation to ensure that all rats ovulated was 45 min. However, stimulation in the arcuate region did not have to be continuous throughout this period. Indeed, three 5-min bursts at 100 Hz distributed equally through 45 min always caused ovulation whereas a continuous 15-min stimulation at the same frequency was without effect. With 30 min of continuous stimulation in the arcuate region, at frequencies ranging from 10 to 100 Hz, approximately half of the rats ovulated.

Anesthesia, General

Fatigue life improvement of nitrogen-ion-implanted pedicle screws.

An experimental study of the fatigue life of pedicle screws and their nitrogen-ion-implanted counterparts was conducted. Nitrogen-ion implantation parameters were varied in the first part of the study to obtain the best implantation characteristics. Using this optimal parameter for N(+)-implantation, the performance of two matched groups were compared at two bending moments near the "knee" of the S-N curves. At 3.96 N-m and 5.09 N-m of applied bending moments, the increase in the mean fatigue life for the former was 98% and for the latter 20%. The 98% prolongation was statistically significant at P less than 0.005; however, the 20% increase was statistically insignificant (P less than 0.1). The implantation depth is about 0.1 mu in the near surface of the screw. This appears to be thick enough to inhibit crack initiation at 3.96 N-m, but only marginally at 5.09 N-m. Increasing the implantation depth has the potential of increasing the fatigue life at the higher bending moments.

Bone Screws