Bhagwan T. Shahani

CARDIOVASCULAR EFFECTS OF CENTRALLY ADMINISTERED ENDOTHELIN-1 AND ITS RELATIONSHIP TO CHANGES IN CEREBRAL BLOOD FLOW

Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng. i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (-40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (-46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on Blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 micrograms, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET receptors.

Painless electrodiagnostic current perception threshold and pain tolerance threshold values in CRPS subjects and healthy controls: a multicenter study.

Abstract: The purpose of this study is to evaluate both painless and painful sensory transmission in patients with Complex Regional Pain Syndrome (CRPS) using the automated electrodiagnostic sensory Nerve Conduction Threshold (sNCT) test. This test generates reliable, painless Current Perception Threshold (CPT) and atraumatic Pain Tolerance Threshold (PTT) measures. Standardized CPT and PTT measures using constant alternating current sinusoid waveform stimulus at 3 different frequencies 5 Hz, 250 Hz, and 2 kHz (Neurometer® CPT/C Neurotron, Inc. Baltimore, MD) were obtained from CRPS subjects at a distal phalange of the affected extremity and at an ipsilateral asymptomatic control site. Matched sites were tested on healthy subjects. Detection sensitivities for an abnormal PTT and CPT test were calculated based on specificity of 90% as determined from data obtained from healthy controls. A Spearman rank correlation was used to test for a significant association between presence of allodynia and an abnormal PTT or CPT at any frequency tested. Thirty‐six CRPS subjects and 57 healthy controls were tested. The highest detection sensitivity of the PTT test from symptomatic test sites was 63% for the finger and 71% for the toe. PTT abnormalities were also detected, to a lesser degree, at the asymptomatic control site (41% finger control site, 16% toe control site). The highest CPT detection sensitivity at the symptomatic site was 37% for the finger site and 53% for the toe site. CPT abnormalities were also detected at the asymptomatic control site (29% finger control site, 37% toe control site). Eighty‐six percent of the CRPS subjects had either a PTT or CPT abnormality at any frequency at the symptomatic site. There was a significant correlation between presence of allodynia and presence of an abnormal CPT and PTT, respectively (P < .01). The correlation coefficient was lower for CPT than for PTT, ie, 0.34 versus 0.6 for the finger and 0.48 versus 0.67 for the toe, respectively. In studied CRPS patients an abnormal PTT was detected with higher sensitivity than an abnormal CPT. Assessing PTT may become a useful electrodiagnostic quantitative sensory test for diagnosing and following the course of neuropathic pain conditions.

Decomposition of EMG signal by wavelet spectrum matching

We have developed a technique using wavelet transform to classify single motor unit (SMU) potentials and to decompose EMG signals into their constituent SMU potentials. The distinction between this technique and previous techniques is that it measures waveform similarity of SMU potentials from wavelet domain which gives this technique many advantages over other techniques. Separation of compound motor unit potentials, on the other hand, is based on a sequence of waveform differential correlation processes. Our technique also utilizes the information on discharge regularities of SMUs. This technique had been tested using actual EMG recordings that were composed of more than 10 different motor unit potentials. The results were satisfactory.

Effect of centrally administered endothelin agonists on systemic and regional blood circulation in the rat: role of sympathetic nervous system

The aims of the present study were to determine (1) the hypotensive and regional circulatory effects of centrally administered endothelin (ET) ETA and ETB agonists, and (2) the role of the sympathetic nervous system in the mediation of hypotensive effects due to centrally administered ET-1. The systemic haemodynamics and regional blood circulation in urethane anaesthetized rats following intracerebroventricular (i.c.v.) administration of ET-1, ET-2, SRT6b, ET-3 and SRT6c (10, 30 and 90 ng) were determined by a radioactive microsphere technique. The effect of centrally administered ET-1 on sympathetic nerve activity was also analysed. Systemic haemodynamics and regional blood circulation were determined before (baseline) and 30 min after administration of ET agonists. Cumulative administration of three doses of saline (5 microliters, i.c.v. at 30 min intervals) did not produce any significant cardiovascular effects. ET-1, ET-2 and SRT6b produced a decrease in blood pressure (51%, 47% and 41%, respectively) along with a decrease in cardiac output (58%, 60% and 45%, respectively) and stroke volume. Heart rate and total peripheral resistance were not affected. ET-1, ET-2 and SRT6b also produced a significant reduction in blood flow to the brain, kidneys, heart, portal, mesentery and pancreas, gastrointestinal tract (GIT) and musculoskeletal system. The effect of ET-2 on the cardiovascular system was less intense in comparison with ET-1 and SRT6b. Centrally administered specific ETB receptor agonists ET-3 and SRT6c did not produce any change in systemic haemodynamics and regional blood flow. Centrally administered ET-1 (90 ng) produced a significant decrease (61%) in sympathetic nerve activity 30 min after drug administration, along with a fall in blood pressure. It is concluded that centrally administered ETA agonists produce significant cardiovascular effects mediating through the sympathetic nervous system.

The relationship between age, gender and psychological distress in rehabilitation inpatients

Although commonly accepted as the dominant emotional reaction to functional loss, the reported occurrence of depression in rehabilitation patients varies widely. Rather than focusing solely on depressive symptoms, this study furthers our understanding of emotional distress following a functional loss by assessing a range of psychiatric symptoms. A series of rehabilitation patients admitted to an urban hospital inpatient unit is used as the sample (n = 48). Demographic, neuropsychological, and a functional independence measure were included as independent variables. The statistical analysis revealed that-although age was not correlated with years of education, functional status, or neuropsychological impairment-there was a significant inverse relationship between age and reported emotional distress. Utilizing MANCOVA to explore the impact of age and gender on specific groups of psychiatric symptoms revealed that both younger and male patients tended to express psychiatric symptoms more frequently. The importance of considering age and gender in evaluation of emotional distress in rehabilitation is supported in this comprehensive study of psychiatric symptoms.

Motor unit discharge behaviors in stroke patients

We studied 60 motor units from abductor pollicis brevis, first dorsal interosseous, and abductor digiti minimus muscles in 18 patients with upper motor neuron lesions. Both fractional process parameters and serial correlation coefficients were estimated. The results suggest that both serial correlation coefficients and fractional process parameters can be used to objectively document upper motor neuron disorders in stroke patients. However, each of them may be more sensitive to distinct central motor regulatory mechanisms.

Motor unit number estimation by spatial-temporal summation of single motor unit potentials

Current techniques for motor unit number estimation (MUNE) rely on the amplitude of the compound muscle action potential (CMAP) evoked by supramaximal stimulation and mean amplitude of single motor unit potentials (SMUPs). The phase cancellation during summation is not considered. We developed a technique to address this issue. Slow and fast types of motor unit potentials were collected from 5 normal subjects from their abductor pollicis brevis muscles by low‐level voluntary contractions, and near‐threshold nerve stimulation, respectively. Two of each type of SMUPs were used as templates for reconstructing the best fitted CMAP using a feed‐forward neural network. The total number of SMUPs simulated from the four templates during the reconstruction served as MUNE. The mean MUNE was 222 ± 98. The technique is simple and noninvasive, and may be applied in the future for MUNE in patients.

Modification of systemic and regional circulatory effects of intracerebroventricular administration of endothelin-1 by propranolol in anesthetized rats.

1. Cardiovascular effects of centrally administered endothelin-1 (ET-1) were studied in control and propranolol-treated anesthetized rats using a radioactive microsphere technique. 2. In the control group, blood pressure, cardiac output, and stroke volume were decreased, and heart rate was not altered after the administration of ET-1.ET-1 produced a reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system, and skin. 3. Propranolol significantly attenuated the decrease in blood pressure, cardiac output and stroke volume induced by centrally administered ET-1. The reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system and skin induced by centrally administered ET-1 was blocked by propranolol. 4. It is concluded that centrally administered ET produces significant cardiovascular effects which are mediated through the sympathetic nervous system and could be antagonized by propranolol. These findings can also be helpful in explaining some of the beneficial effects of propranolol in various cardiovascular disorders involving central ET mechanisms.

Study of single motor unit discharge patterns using 1/f process model

We developed a technique to study temporal discharge patterns of single motor units using 1/f process model, whose fractional parameter γ was shown to be a useful indicator for distinguishing between discharge behaviors of single motor units of normal subjects and patients with upper motor neuron lesions. We have studied a total of 47 motor units in 3 normal subjects, and 41 in 3 patients with upper motor neuron lesions from biceps and extensor digitorum communis muscles during steady contraction. The parameter γ was estimated with an algorithm based on wavelet analysis. The mean value of γ in patients was 1.52, and the mean value of γ in normal subjects was −0.06. These results suggest that 1/f process can be used to document the impaired motor control mechanisms at single motor unit level.

Separation of superimposed EMG potentials using expansion matching technique

We have developed a new method using the expansion matching technique to separate compound electromyographic (EMG) potentials based on template matching. This technique has been integrated as part of a software package for EMG signal decomposition. It has been tested using actual EMG recordings, which were composed of more than 10 different single motor unit potentials.