Attempt to prevent doxorubicin-induced acute human myocardial morphologic damage with acetylcysteine.

Doxorubicin induced acute as well as chronic myocardial morphologic alterations. Twenty patients with normal cardiovascular function were randomized to 2 groups based on age and dose of doxorubicin. Group I received placebo 1 hour before doxorubicin administration; group II received acetylcysteine (N-acetyl-L-cysteine) (Nac) 1 hour before doxorubicin. Endomyocardial biopsies were performed at base line at 4 and 24 hours after doxorubicin administration. Biopsy tissue was viewed by electron microscopy, and stereoscopic techniques were used to determine tubular and mitochondrial area. The change of the tubular area was similar in the 2 groups, was maximum at 4 hours, and was proportionately spread throughout the cell. The mitochondrial swelling was also similar in the 2 groups and proportionate throughout the cell but was maximum at 24 hours. This study demonstrated that the acute doxorubicin-induced damage was diffuse and not prevented by Nac.

Effects of apomorphine on the rabbit electroretinogram.

Experiments were conducted in both albino and pigmented rabbits to determine the effects of apomorphine on the electroretinogram (ERG). Injection of apomorphine (0.1 to 1.5 mg/kg) into the left carotid artery produced dose-related decreases in the b-wave, predominantly in the b2-wave amplitude, and also increases in the c-wave amplitude. No significant changes were observed in the a-wave amplitude or in the attendant latencies. The ERG changes apparently were not related to systemic drug effects. The effects of the drug were similar for both albino and pigmented rabbits. Apomorphine, a dopamine agonist, has the opposite effect on the b2-wave of the ERG when compared with the effect of chlorpromazine, a dopamine antagonist. Involvement of dopamine receptors is not unexpected, since the retina is rich in dopamine, especially in the inner plexiform layer.

Influence of chlorpromazine on the rabbit electroretinogram.

In anesthetized albino or nonalbino rabbits, a 3 to 8 mg/kg IV injection of chlorpromazine did not affect a-wave amplitude of the electroretinogram (ERG). However, immediately after the injection of the drug, b-wave amplitude increased. The maximum increase occurred between 35 to 50 min, and the recovery time varied between 5 to 8 hr. Initial changes in the b-wave amplitude to some extent were affected by systemic changes in the blood pressure. However, the b-wave amplitude remained high for a long time after the blood pressure reached preinjection value, indicating a local effect of the drug. There was no change in a- or b-wave latencies. Although in vitro a large quantity of chlorpromazine can be localized in the melanin granules from pigmented rabbit retina, in vivo the ERG b-wave changes caused by the small intravenous dose of the drug were similar in both albino and nonalbino rabbits.

A method for collecting semithin epoxy serial sections for light microscopy and 3-D reconstruction.

In the three-dimensional reconstruction of neuronal structure, it is imperative that ribbons of semithin or ultrathin sections be obtained. Resin-embedded semithin sections display better structural details than paraffin-embedded sections. The cutting and collecting of long ribbons of resin-embedded semithin sections using a microtome, requires the use of large troughs on glass knives. A simple plastic trough has been described which facilitates the collection of ribbons directly onto a coverslip. As the ribbons are formed, they are floated on a coverslip. The water in the trough is slowly drained through a tubing which is attached to a syringe. The ribbons settle on the coverslip, which is easily removed and placed on a hotplate to dry the sections.

Collection and handling of ultrathin serial sections for 3-dimensional reconstruction.

Serial sectioning for 3-D reconstruction requires a highly skilled and experienced individual to collect ribbons of ultrathin sections on formvar-coated grids, and to handle the grids after section collection. A simple method is described for placing ribbons in an orderly serial fashion on formvar-coated grids, by a microtomist with average experience. Prior to sectioning, a wax ledge is prepared on the sloping edge of a glass knife in order to support a formvar-coated grid held in a horizontal slot cut in the wax. After a ribbon is formed, the water in the trough is slowly withdrawn to allow the ribbon to settle on the grid. The grids are then placed in an easy-to-make plastic chamber so that the formvar does not get ruptured during drying. The chamber can also be used for staining and storage of grids thereafter. Approximately 4000 sections from mudpuppy retinal cells have been successfully collected using this method. Computer 3-D reconstruction of the individual cells has been done.

Pattern generator system as a versatile visual stimulator.

We have designed and implemented a Motorola 68000 microprocessor-based pattern generator system (PGS) that uses a color video display terminal (VDT) to provide light stimuli to the intact vertebrate retina. This communication is intended for those who are considering acquisition of a commercial retinal stimulator or those who are custom designing their own pattern generator system. The discussion surveys the features to be included as well as design factors which must be considered in such a device. The memory organization of the PGS allows as stimuli multiple, complex patterns consisting of one or more disks, annuli, bars or gratings to flash or modulate in intensity according to a pre-defined function. In addition, patterns can move smoothly in any direction at selectable, uniform speeds without the re-drawing of video memory. The presence of a 12-bit A/D converter internal to the PGS allows a dynamic change in stimulus position, speed or pattern based upon physiological feedback. A physically realistic image size (0.9 cm2) and resolution (20 mu/pixel) in the retinal plane are achieved with simple intervening optics. The video field rate of 60 Hz is above the flicker fusion frequency for most vertebrate animals and does not induce artifacts in cellular responses. The PGS operating in a PC-based environment meets the requirements of a versatile optical stimulator for investigations in retinal electrophysiology.

Depolarization of membrane potential and the smooth muscle contraction by isothiocyanatobenzyl imidazoline in guinea-pig stomach circular muscle.

Isothiocyanatobenzyl imidazoline (IBI) produces characteristic slowly developing contraction of many smooth muscle preparations including the circular smooth muscle of the guinea-pig stomach. Changes in the membrane potential were recorded intracellularly, and the muscle contraction induced by IBI was investigated. IBI at 100 micromol/l slowly produced a sustained depolarization of the membrane with a maximum change of approximately 15 mV. This depolarization could not be blocked by 1-hyoscyamine, 100 nmol/l. An imidazoline analogue, oxymetazoline at 1 micromol/l, did not change the resting membrane potential as observed after IBI. Significant membrane depolarization after IBI still occurred in Ca2+-free medium. During IBI-induced depolarization, sudden reduction of Na+ to 30 mmol/l in the medium reduced the depolarization slightly. IBI-induced depolarization was additive with that produced by 20 mmol/l K+ in the medium. In the presence of tetraethylammonium chloride or levcromakalim or nifedipine, IBI continued to depolarize the membrane although functional pharmacological experiments showed that the contractile effects of IBI were significantly inhibited by 30 micromol/l levcromakalim and abolished by 100 nmol/l nifedipine. At 100 micromol/l phentolamine (reported by others as an inhibitor of ATP-sensitive potassium channels) completely blocked IBI-induced contraction. Phentolamine (30 micromol/l) blocked the contractile effects of IBI by 50%. On the other hand, S(-)-Bay K 8644, a voltage-dependent calcium channel activator, was additive with the contractile response of IBI. These results indicated that IBI produced membrane depolarization and contraction of the guinea-pig stomach circular muscle, by a mechanism not involving muscarinic receptors or alpha-adrenoceptors. Even though levcromakalim, an ATP-sensitive potassium channel opener, could not inhibit IBI-induced depolarization, the ATP-sensitive potassium channel and the voltage-dependent calcium channel may be intrinsically linked with the action of IBI.

Wavelet analysis of electromyography for back muscle fatigue detection during isokinetic constant-torque exertions.

STUDY DESIGN: An investigation of the effects of human trunk extensor muscle fatigue on the temporal change in frequency content of the electromyogram as quantified using the Fourier and wavelet transforms during the performance of repetitive dynamic trunk extension. OBJECTIVE: To evaluate whether alterations in the Fourier and wavelet transform measures were consistent with a shift of the signal power to lower frequencies, and to determine which measures were more highly correlated with the decline in maximal trunk extension torque. SUMMARY OF BACKGROUND DATA: Objective assessment of trunk muscle fatigue is likely to play a more important role in the rehabilitation and prevention of low back injuries, given the association between lack of trunk muscle endurance and acquisition of low back pain. Validation of new methods designed to quantify the level of fatigue using the surface electromyogram is necessary before these techniques can be used in industrial rehabilitation settings. The wavelet transform is a recent development in the signal processing of electromyograms that shows promise as a method for assessment of fatigue. METHODS: Trunk muscle electromyograms obtained from study participants performing repetitive isokinetic trunk extension endurance tests were analyzed using the wavelet and the traditional Fourier methods. Trunk extension torque was controlled at 35% and 70% of the participants' maximal voluntary contraction while they exerted at 5 and 10 repetitions per minute. The decline in maximal trunk extension torque was measured once per minute. Linear regression quantified the rate of change in Fourier and wavelet measures caused by fatigue, whereas Pearson's correlation coefficient determined their association with the decline in maximum torque. RESULTS: Changes in the characteristics of the electromyogram were consistent with a shift to lower frequencies: The signal power at higher frequencies was reduced, whereas the power at lower frequencies was elevated. The amount of change was dependent on the task conditions (exertion level and repetition rate). The wavelet-based measures demonstrated as strong an association with the decline in maximal torque output as the Fourier-based measures. CONCLUSIONS: This study demonstrates that assessment of trunk muscle fatigue during isokinetic movementis possible using both Fourier and wavelet measurements. However, the methods were not as likely to change significantly during lower rates of exertion. These methods, when implemented in a controlled setting, may be used to document the rehabilitation process and guide preventive exercise training.

Simulation of cardiac conduction system in distributed computer environment.

A high resolution, three dimensional, computer model of the cardiac conduction system has been developed. Cardiac geometry was constructed from sectional images of VHP project of the National Library of Medicine. The heart was modeled as a matrix of cells that fill its anatomical structure. The intracellular distance was 1 mm and the total number of cells were 457,482. Electrophysiological parameters like action potential, absolute refractory period and conduction velocity were assigned to each of the cells. The pattern of the excitation sequence propagation as well as potentials on the body surface points were computed on a single processor. The working memory and the time for computation of the algorithms were minimized using efficient data structures. The time to compute an excitation sequence over one cardiac cycle was 4 hours. The algorithms were also implemented on a distributed network of personal computers running on a QNX operating system. The speed of computation of the excitation sequence algorithm was improved by a factor of 2.52 when the algorithm was implemented on a network of three Intel-66 MHz machines.

Wavelet analysis of electromyography for back muscle fatigue detection during dynamic constant-torque exertions.

The fatigue of the back muscles appears to be strongly implicated as a risk factor for acquisition of low back pain, which is one of the leading ills of our industrial society. Previously, researchers have successfully measured the level of muscular fatigue by using the Fourier transform to analyze the frequency content of the electromyogram (EMG). However, due to the requirement that the EMG signal be stationary, the Fourier transform is suitable only for the analysis of static muscle exertions in which the muscle is held at constant length and tension. Because the majority of industrial work tasks are not static in nature, new methods for quantifying fatigue during dynamic work are needed. The wavelet transform is a novel, although mathematically well developed, technique for analyzing non-stationary signals that has only recently been applied to the study of EMG. Consequently, the main objective of this project is to develop techniques, using the wavelet transform, for the quantification of back muscle fatigue during dynamic repetitive working conditions.

Wavelet and short-time Fourier transform analysis of electromyography for detection of back muscle fatigue.

Measurement of the time-varying characteristics of the frequency content of trunk muscle electromyography is a method to quantify the amount of fatigue endured by workers during industrial tasks, as well as a tool that may guide the training and rehabilitation of healthy and injured workers. Quantification of the change of signal power within specific frequency ranges may shed greater insight into the fatigue process. Sixteen healthy male subjects performed isometric trunk extension at 70% of their maximum voluntary contraction. Surface electromyography from medial and lateral erector spinae, and latissimus dorsi locations were processed using the short-time Fourier transform (STFT) and wavelet transform. Linear regression quantified the time rate of change of median frequency as well as frequency specific STFT filter and wavelet scale measures. The median frequency from the short-time Fourier transform declined by 22 Hz/min from an initial value of 77 Hz on average. The wavelet and STFT filter measures demonstrated this decline to be caused by a reduction in 209-349 Hz signal power in addition to an increase in 7-88 Hz signal power. A significant reduction in median frequency and significant elevation in 13-22 Hz wavelet signal component was detected in about 90% of the cases, indicating their use for detecting and quantifying fatigue.

Wavelet analysis of SAECG to identify patients with conduction defects at risk for sudden cardiac death.

The aim of this study was to determine how Wavelet transform analysis of signal-averaged ECGs can identify patients with conduction defects who are at high risk for development of ventricular tachycardia. In this study, 34 SA-ECGs and programmed electrical stimulation (PES) reports were obtained from the OSU Department of Cardiology Database (1988-1996) and divided into two groups: 17 patients that had inducible monomorphic VT by PES (VT+) and 17 that showed no arrhythmias (VT-). We used Morlet's wavelet to analyze the X, Y, Z, and RMS vector magnitudes in each group. The mean duration from the peak of the RMS vector magnitude to the QRS offset was statistically different with a T value (2-tailed distribution, unequal variance) of 0.033. We noted statistically significant (p < 0.0001) differences in Wavelet energies for 44 msec after the peak of the RMS vector magnitude largest in the Z lead, the first 22 msec, and frequency bins less than 131 Hz. Although no clinical marker could be determined using Wavelet analysis to distinguish the the VT+ from the VT- group, the results from this study show that their SA-ECGs are indeed different even though the optimal analysis has not yet been devised.

Development of a multichannel electrochemical centrifugal analyzer.

A new instrument has been developed that is similar in design and concept to the GeMSAEC centrifugal analyzer (Oak Ridge National Laboratory) except that electrochemical detection is used rather than optical detection. The present version has eight channels, each with its own detector. Problems of speed control and sampling synchronization are greatly minimized from those of a multichannel centrifugal analyzer having a single detector system. All eight sample compartments and polarographic cells are contained in a single Teflon rotor, 7.7 cm in diameter. The working electrodes are planar carbon electrodes. The initial application of the analyzer is in kinetic methods involving the rates of enzyme-catalyzed reactions. The initial system chosen was the glucose oxidase system. When the rotor is spun, the solution moves into the sample cell and up against the planar working electrode. The reaction starts and current is measured as a function of time at a constant applied voltage. The current output from each polarographic circuit is connected to a separate channel of a multiplexed analog-to-digital converter. The analyzer is controlled by a dedicated microcomputer system, which sets the polarographic cell voltages, collects the current-time data, and calculates the results.