Oscar U. Scremin

Increasing muscle mass in spinal cord injured persons with a functional electrical stimulation exercise program

OBJECTIVE To determine the magnitude of changes in muscle mass and lower extremity body composition that could be induced with a regular regimen of functional electrical stimulation (FES)-induced lower-extremity cycling, as well as the distribution of changes in muscle mass among the thigh muscles in persons with spinal cord injury (SCI). STUDY DESIGN Thirteen men with neurologically complete motor sensory SCI underwent a 3-phase, FES-induced, ergometry exercise program: phase 1, quadriceps strengthening: phase 2, progressive sequential stimulation to achieve a rhythmic pedaling motion (surface electrodes placed over the quadriceps, hamstrings, and gluteal muscles); phase 3, FES-induced cycling for 30 minutes. Participants moved from one phase to the next when they met the objectives for the current phase. MEASURES Computed tomography of legs to assess muscle cross-sectional area and proportion of muscle and adipose tissue. Scans were done at baseline (before subjects started the program), at first follow-up, typically after 65.4+/-5.6 (SD) weekly sessions, and at second follow-up, typically after 98.1+/-9.1 sessions. RESULTS Increases in cross-sectional areas were found in the following muscles: rectus femoris (31%, p<.001). sartorius (22%, p<.025), adductor magnus-hamstrings (26%, p<.001), vastus lateralis (39%, p = .001), vastus medialis-intermedius (31%, p = .025). Cross-sectional area of adductor longus and gracilis muscles did not change. The ratio of muscle to adipose tissue increased significantly in thighs and calves. There was no correlation among the total number of exercise sessions and the magnitude of muscle hypertrophy. CONCLUSIONS Muscle cross-sectional area and the muscle to adipose tissue ratio of the lower extremities increased during a regular regimen of 2.3 FES-induced lower extremity cycling sessions weekly. The distribution of changes was related to the proximity of muscles to the stimulating electrodes.

Cerebrovascular Anatomy and Blood Flow Measurements in the Rabbit

The arterial supply and venous drainage of the rabbits brain were characterized by intravascular injection of casting material and intra-arterial administration of markers (crystal violet or dissolved hydrogen gas). The internal carotid artery supplies the homolateral cerebral cortex and subcortical structures except for the thalamus and the posterior portion of the nucleus caudatus; it also supplies the homolateral retina and optic nerve. No noncerebral structures are supplied by this artery. The dorsal sagittal sinus drains the dorsal and lateral parts of the frontal and parietal areas of the cerebral cortex, with no detectable extracerebral contamination. Electromagnetic measurement of flow in the internal carotid artery (ICBF), volumetric or H2-clearance measurement of flow in the dorsal sagittal sinus (SSBF), and H2-clearance determination in cerebral cortex yield comparable results on the cerebrovascular response to hyper- and hypocapnia. ICBF and SSBF are reliable and valid estimates of average blood flow through the homolateral cerebral hemisphere and the cerebral cortex, respectively.

Gastric Mucosal Blood Flow Response to Stimulation and Inhibition of Gastric Acid Secretion

The effect of stimulation (with graded doses of intravenous pentagastrin) and inhibition (with an H2-blocker or a proton pump inhibitor) of acid secretion on corpus mucosal blood flow was investigated. Hydrogen gas clearance was used to measure blood flow in the basal portion of the mucosa of anesthetized rats. A dose-related increase in acid output increments above resting level was observed with the doses of pentagastrin from 0 (saline infusion) to 40 micrograms/kg.h. With the doses of pentagastrin from 0 to 80 micrograms/kg.h there was a dose-related increase in mucosal blood flow increments above resting levels. A linear correlation (r = 0.7) was observed between increments in acid output and increments in mucosal blood flow with increasing doses of pentagastrin from 0 to that producing maximal acid secretion (40 micrograms/kg.h). Inhibition of pentagastrin-stimulated acid secretion by cimetidine or omeprazole returned stimulated gastric mucosal blood flow to baseline levels.

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Abstract Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 µg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%–84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin.

Methods for estimating the proper length of a cane

OBJECTIVE To find a practical method of cane length measurement that achieves the elbow flexion of 20 degrees to 30 degrees. DESIGN Two standard methods of cane length measurements were compared. Method I: Length of the cane measured from the floor to the top of the greater trochanter. Method II: Length of the cane measured from the floor to the distal wrist crease. Using an adjustable cane, each individual was fitted according to the two methods, and elbow angle was measured after each adjustment. Cane length was also correlated with arm length and height. PARTICIPANTS Fifty-two normal volunteers who were ambulatory without assistive devices. RESULTS Mean +/- SD of the elbow angle according to Method I and Method II was 44.8 +/- 11.8 and 25.4 +/- 6.1, respectively. A significant difference was found in the elbow angle between the two methods (unpaired two-tailed student t test, p = 5.910(-18)). Of the 52 volunteers, 4 (7.7%) measured according to method I and 49 (94.3%) measured according to method II showed the elbow angle between 20 degrees and 30 degrees. The ideal length of the cane (L) also can be determined by the formula L = H x .45 + .87 meters or A x .76 + .19 meters, where H is the height of the individual in meters and A is the arm length measured in meters. CONCLUSION Ideally, cane length should be measured from the floor to the distal wrist crease. The length can also be determined using the above formulae.

Functional brain mapping in freely moving rats during treadmill walking.

A dilemma in functional neuroimaging is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. Recently, we developed an implantable microbolus infusion pump (MIP) that allows bolus injection of radiotracers by remote activation in freely moving, nontethered animals. The MIP is examined as a tool for brain mapping in rats during a locomotor task. Cerebral blood flow–related tissue radioactivity (CBF-TR) was measured using [14C]-iodoantipyrine with an indicator-fractionation method, followed by autoradiography. Rats exposed to walking on a treadmill, compared to quiescent controls, showed increases in CBF-TR in motor circuits (primary motor cortex, dorsolateral striatum, ventrolateral thalamus, midline cerebellum, copula pyramis, paramedian lobule), in primary somatosensory cortex mapping the forelimbs, hindlimbs and trunk, as well as in secondary visual cortex. These results support the use of implantable pumps as adjunct tools for functional neuroimaging of behaviors that cannot be elicited in restrained or tethered animals.

Cholinesterase Inhibition Improves Blood Flow in the Ischemic Cerebral Cortex

The ability of central cholinesterase inhibition to improve cerebral blood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo- 14C-antipyrine autoradiography in 170 regions of cerebral cortex. The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions. The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine.

Hypertension in β-Adducin–Deficient Mice

Abstract —Polymorphic variants of the cytoskeletal protein adducin have been associated with hypertension in humans and rats. However, the direct role of this protein in modulating arterial blood pressure has never been demonstrated. To assess the effect of β-adducin on blood pressure, a β-adducin–deficient mouse strain (−/−) was studied and compared with wild-type controls (+/+). Aortic blood pressure was measured in nonanesthetized, freely moving animals with the use of telemetry implants. It is important to note that these mice have at least 98% of C57Bl/6 genetic background, with the only difference from wild-type animals being the β-adducin mutation. We found statistically significant higher levels of systolic blood pressure (mm Hg) (mean±SE values: −/−: 126.94±1.14, n=5; +/+: 108.06±2.34, n=6; P ≤0.0001), diastolic blood pressure (−/−: 83.54±1.07; +/+: 74.87±2.23; P ≤0.005), and pulse blood pressure (−/−: 43.32±1.10; +/+: 33.19±1.96; P ≤0.001) in β-adducin–deficient mice. Western blot analysis showed that as a result of the introduced genetic modification, β-adducin was not present in heart protein extracts from −/− mice. Consequently, this deficiency produced a sharp decrease of α-adducin and a lesser reduction in γ-adducin levels. However, we found neither cardiac remodeling nor modification of the heart function in these animals. This is the first report showing direct evidence that hypertension is triggered by a mutation in the adducin gene family.

Cholinergic Cerebral Vasodilatation in the Rabbit: Absence of Concomitant Metabolic Activation

Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O–30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects, It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.

The Electroencephalogram, Blood Flow, and Oxygen Uptake in Rabbit Cerebrum

In the present study, the relationships among electroencephalographic (EEG) amplitude shifts, cerebral blood flow (CBF), and cerebral oxygen uptake (CMRO2) have been characterized in halothane-anesthetized rabbits. CBF was measured by timed collection of venous effluent from the superior sagittal sinus. CMRO2 was calculated as the product of CBF and the arteriovenous difference in oxygen content. The depth of anesthesia in the first series of experiments was maintained at a constant level that was characterized by spontaneous EEG shifts from high- to low-voltage states (HV-LV shifts). These shifts were associated with transient decreases in mean arterial pressure (MAP), which averaged 23 ± 2 mm Hg (n = 17). Ninety seconds after spontaneous HV-LV shifts, MAP had returned to its original value, CBF had increased by 26 ± 7% (n = 8), and CMRO2 had increased 22 ± 4% (n = 7). In a second series of experiments, HV-LV shifts were induced by a 90-s application of a standardized nociceptive stimulus (n = 13). Following these stimulation-induced HV-LV shifts, CBF increased 28 ± 5% and CMRO2 increased 27 ± 4%. Under scopolamine (0.35 mg/kg, i.v., n = 8), no change in CBF was observed following HV-LV shifts induced by 90-s of stimulation, although CMRO2 increased significantly by 14 ± 3%. After 300 s of post-scopolamine stimulation, however, both CBF and CMRO2 had significantly increased by 12 ± 3 and 15 ± 3% (n = 8) of control, respectively. These results demonstrate that HV-LV shifts, whether spontaneous or stimulation-induced, are associated with significant increases in both CBF and CMRO2. Because the early (90-s) increases in CBF but not those in CMRO2 could be blocked by scopolamine, we suggest that the cerebral vasodilatation that occurs during the early phase of HV-LV shifts involves cholinergic mechanisms. Because scopolamine could not block the increase in CBF observed after 300 s of stimulation, we suggest that the final value of CBF obtained after an HV-LV shift is determined by a combination of both cholinergic and noncholinergic factors.