The change of the rate-controlling processes with temperature in the hydration of anhydrous nedocromil sodium by water vapor.

A six-stage model is proposed to describe the overall process of sorption of water vapor on and into anhydrous nedocromil sodium. The way in which temperature, pressure, and time affect the rate of reaction for each of the stages has been analyzed. Experimental data for the measured rates, where temperature, pressure, and time are variables, are compared with the predictions obtained from each of the six stages. The most useful comparator is a graphical representation of reduced time versus hydration rate. The theoretical equations presented as a shape analysis of the experimental curves show the process to have different controlling mechanisms in three temperature regions: up to 27 degrees C, hydration is controlled by a nucleation and growth mechanism; between 27 and 31 degrees C, the process is dominated by diffusion of water molecules into the crystal; and >31 degrees C, neither nucleation nor diffusion are controlling but some, as yet, undetermined physical processes.

Adsorption of water by anhydrous nedocromil sodium from 20 to 40 degrees C.

Three different powder preparations of the drug disodium 9-ethyl-4, 6-dioxo-10-propyl-4H,6H pyrano[3,2-g]quinoline-2,8-dicarboxylic trihydrate, Nedocromil sodium (trade name Tilade), have been fully dehydrated in a vacuum and their water vapor adsorption characteristics quantitatively assessed at different water vapor pressures over a temperature range 20 to 40 degrees C. At saturated vapor pressures, 100% RH, rates of adsorption are around 0.1 s(-1/2). Graphs of square root of time against reduced mass during uptake of water vapor at vapor pressures in the range 20 to 47 mm of Hg, all equivalent to 100% RH, indicate control by a diffusion mechanism with activation energies in the range 8 to 24 kJ mol(-1), dependent on the powder preparation method. In two of the powders nonlinear Arrhenius-type plots are interpreted as showing that control of the process is dependent on the surface's ability to hold water molecules at the experimental temperature. The variation in activation energies and the calculated values for diffusivities, around 1 x 10(-13) m(2) s(-1), are used to explore structural involvement in the overall water adsorption process. The measured values of water vapor diffusivity into the structure have been used to predict the water solubility of nedocromil sodium trihydrate, and the results show good agreement to reported solubilities. This approach to solubility prediction is an alternative to the Noyes and Whitney method where ions leaving the surface are monitored.

Periodic posture stimulation of the baroreceptors and the local vasomotor reflexes.

In a supine subject, lowering of the foot from heart level to 50 cm below is known to stimulate the local reflex response and the baroreceptor outflow. We lowered and raised the leg of a supine subject periodically, with the leg stationary between movements (square wave). The Traube-Hering-Mayer wave (THM congruent to 0.1 Hz) was captured by or locked on to the leg movement over a certain frequency range, this is usually called the entrainment range. Square wave periodic leg movement in this manner on 10 male subjects, mean age 22 years, demonstrated that the THM frequency can be entrained. The lower limit of the entrainment bandwidth is 0.0841 (SD 0.0030) Hz and the upper limit is 0.1176 (SD 0.0013) Hz. Further examination showed that this phenomenon is independent of the breathing input. Comparison with the Traube-Hering-Mayer entrainment techniques of breathing and periodic neck suction using the Eckberg collar which stimulates the baroreceptors showed similar results. This work supports the hypothesis that the local reflex response and the baroreceptor outflow entrain the THM frequency.

Quantitative measurement of sympathetic neuropathy in patients with diabetes mellitus.

Vasoconstriction occurs in the skin capillary blood flow of the healthy subject when posture changes from supine to standing. Using frequency analysis of the optical photoplethysmograph signal, a statistically significant difference (P less than 0.01) may be demonstrated between supine and standing positions in the lower frequency band (0.01-0.5 Hz) in the foot of normal subjects. This allowed us to develop a simple index: sympathetic power band change (SPBC). Patients with diabetes mellitus often suffer from degeneration in the sympathetic nervous system. This impairs the normal vasoconstrictor response to standing. We have applied the SPBC 'blind' to a group of diabetic patients. Such patients may be divided into three groups according to their SPBC indices: normals with SPBC greater than 2.6 (group A), intermediates with 2.6 greater than or equal to SPBC greater than or equal to 0.26 (group B) and poor with SPBC less than 0.26 (group C). All patients with retinopathy were in group C and five out of the six patients with electrophysiologically confirmed peripheral neuropathy were in group C. Frequency analysis of the photoplethysmograph signal has produced an index of sympathetic tone change when subjects move from supine to standing position. The application of this index to patients with diabetes mellitus shows some patients to have sympathetic vascular tone failure.

Skin photoplethysmography--a review.

The photoplethysmograph has been used for over 50 years but there are still misconceptions in how and what is the information obtained. A photoplethysmograph signal from any site on the skin can be separated into an oscillating (a.c.) and a steady-state (d.c.) component, their amplitudes dependent upon the structure and flow in the vascular bed. Many simple applications are available: pulse counters, using the a.c. component, skin colour and haemoglobin saturation meters, using the d.c. component. The d.c. component of the photoplethysmograph signal is a function of the blood flux beneath the device. A good emitter for use in a photoplethysmograph of skin blood flow is one in the frequency range 600-700 nm and the best signal for a.c. analysis is obtained from the finger pulp. The frequency range of the electronic circuitry should be from 0.01 to 15 Hz, then all the information in the signal can be extracted about the autonomic nervous system control of the cardiovascular system, particularly between 0.01 and 2 Hz. Comparative studies may be drawn between similar skin sites on a subject or between subjects if the afferent inputs to the brain stem are controlled or driven at a known frequency. These afferents, inputs, will modulate the efferents, outputs, which generate variations in the a.c. component of the detected photoplethysmograph signal.

The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion.

The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.

Modelling of the control of heart rate by breathing using a kernel method.

The process of the breathing (input) to the heart rate (output) of man is considered for system identification by the input-output relationship, using a mathematical model expressed as integral equations. The integral equation is considered and fixed so that the identification method reduces to the determination of the values within the integral, called kernels, resulting in an integral equation whose input-output behaviour is nearly identical to that of the system. This paper uses an algorithm of kernel identification of the Volterra series which greatly reduces the computational burden and eliminates the restriction of using white Gaussian input as a test signal. A second-order model is the most appropriate for a good estimate of the system dynamics. The model contains the linear part (first-order kernel) and quadratic part (second-order kernel) in parallel, and so allows for the possibility of separation between the linear and non-linear elements of the process. The response of the linear term exhibits the oscillatory input and underdamped nature of the system. The application of breathing as input to the system produces an oscillatory term which may be attributed to the nature of sinus node of the heart being sensitive to the modulating signal the breathing wave. The negative-on diagonal seems to cause the dynamic asymmetry of the total response of the system which opposes the oscillatory nature of the first kernel related to the restraining force present in the respiratory heart rate system. The presence of the positive-off diagonal of the second-order kernel of respiratory control of heart rate is an indication of an escape-like phenomenon in the system.

Automation of a cryopreservation apparatus.

An organ preservation apparatus was interfaced to a process-control computer and automated. The flexibility of the equipment was demonstrated by running simultaneous dual sets of experiments under multiple and variable conditions. The computer-control program was written in a new high-level language, Real Time Extended Basic (RTEB), which allowed interactive calibration of the instruments, accurate control of variables, and modification of parameters during run time. A series of preliminary tests in the areas of normothermia, hypothermia, cooling of isolated rat hearts, and cryoprotectant toxicity were performed successfully. This work describes the apparatus and computer program in use.

Spectral analysis of electrocardiogram signals of the isolated guinea pig heart for the detection of arrhythmias.

Fast Fourier Transform analysis of the electrocardiogram (ECG) signal of the isolated guinea pig heart has been used to investigate the subtle ECG changes that precede cardiac arrhythmias. During prolonged periods of regular contractile activity, spectral analysis of the isolated guinea pig heart ECG revealed that the major frequency components were evenly distributed over the range 0-64 Hz. Prior to arrhythmias or during ischaemia however, there was a major reduction in the amplitude of the higher frequency components. Thus, Fast Fourier Transform analysis of an ECG record enables the detection of the subtle ECG configuration changes that precede cardiac rhythm disturbances. The potential application of this technique for the prediction of cardiac arrhythmias is discussed.

Fourier analysis of isolated rat heart electrocardiographs as a measure of viability after cooling to - 22 degrees C with the aid of a cryoprotective agent.

The viability of isolated rat hearts cooled to - 22 degrees C with the aid of a cryoprotective agent, ethylene glycol, has been assessed by a novel technique of comparing the Fourier analysed spectrum of the electrocardiogram before and after cooling. The frequency spectrum of the electrocardiogram of a good isolated heart being retrograde perfused at 37 degrees C, contains 3 peaks with the second harmonic dominant is power. A damaged heart contains higher harmonics and additional components.

Computer control of a modified Langendorff perfusion apparatus for organ preservation using cryoprotective agents.

The construction of an isolated rat heart cryopreservation apparatus which is interfaced to a process-control computer is described. The flexibility of the equipment is demonstrated by the running of simultaneous dual sets of experiments under multiple and variable conditions. The computer-control program allows interactive calibration of the instruments, accurate control of variables and modification of parameters during the experiments. By controlling the speed of the perfusate's peristaltic pump, perfusion pressure was not allowed to exceed a present level. Experiments are reported which allow the storage of hearts at -22 degrees C with the aid of the cryoprotective agents, ethylene glycol.

Variations in vascular resistance of isolated rat hearts during normothermic and hypothermic experiments.

The flexibility of an automated, modified Langendorff perfusion column is illustrated by a series of experiments on isolated rat hearts under the following conditions:L normothermia, hypothermia, the addition of a cryoprotective agent--ethylene glycol and cooling to -13 degrees C and -22 degrees C. Successful normothermic perfusions of up to 14 h were achieved. Hypothermia prevented a rise in vascular resistance with time and improved the electrocardiograms. Ethylene glycol was administered during the cooling period to -22 degrees C at temperatures below 23 degrees C. It was removed upon warming and before toxic effects were visible, thus leading to good recovery. By controlling the speed of the perfusate's peristaltic pump, the perfusion pressure was not allowed to exceed a pre-set level. A constant and standard vascular resistance at any selected perfusion temperature, normal heart rate and electrocardiograms were the criteria for normality.

A thermal entrainment device for cardiovascular investigation.

Information on the temperature control mechanism of the body can be obtained from several body parameters such as the irregularities of the heart beat. Entrainment of the temperature control mechanism occurs when air is alternately heated and cooled as it passes over a subject's limb. The fluid flow, timing circuits and measuring devices for this experiment are described in detail. Experiments were carried out on normal healthy adults resting and during recovery from heavy exercise. Electrocardiogram and optical plethysmography of the little finger were analysed by Fast Fourier Transform. Entrainment occurs with period times between 8s and 80s with the best entrainment occurring at a period time of 30s. The value of the work and the areas presently under investigation are outlined.