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Labyrinthine influence on cat forelimb motoneurons.

1. Intracellular responses in forelimb motoneurons to electrical stimulation of the whole labyrinth and of individual semicircular canal nerves were studied in decerebrated, unanesthetized cats. 2. Stimulation of the whole labyrinth typically produced EPSPs, usually bilaterally, in forelimb extensor (LON, LAT, MED) and shoulder (SI) motoneurons and bilateral IPSPs in forelimb flexor (BIC) motoneurons. 3. Latencies of PSPs indicated that most of those in extensor motoneurons were trisynaptic and many seen in flexor motoneurons may involve four synapses. 4. In the cells sampled, stimulation of the anterior, horizontal or posterior canal nerves often evoked EPSPs in extensor and IPSPs in flexor motoneurons, both ipsi- and contralaterally. Responses to canal stimulation were weaker and more variable than those to stimulation of the whole nerve. 5. Transection of the MLF in the lower medulla had no effect on PSPs evoked in forelimb motoneurons. Lesions in the medulla in the area of the LVST greatly reduced the occurrence of contralateral EPSPs in extensor and IPSPs in flexor motoneurons. The pathway linking labyrinths to forelimb motoneurons therefore appears to include the LVST. Hemisection shows that the pathway to contralateral motoneurons descends in the cord on the side of the stimulated labyrinth before crossing to influence these cells. 6. Labyrinthine control of forelimb motoneurons is less direct than control of neck and back motoneurons. It is suggested that the interneuron in the pathway to forelimb motoneurons is the site of integration of labyrinthine with other reflexes.

Animals↗

Conditioned and unconditioned forelimb reflex systems in the cat: involvement of the intermediate cerebellum.

Temporary inactivation of the cerebellar interposed nuclei was used to assess the role of the intermediate cerebellum in the performance of forelimb cutaneo-muscular reflexes in the cat. The following types of reflexive responses were evaluated: the classically conditioned and unconditioned forelimb withdrawal responses and the forelimb tactile placing, hopping and magnet responses. The experiments tested the hypothesis that the intermediate cerebellum is involved in the performance of all the above forelimb reflexes. The forelimb withdrawal reflex was classically conditioned in a newly developed paradigm in which animals were first operantly conditioned to stand on four elevated platforms. Trained animals were microinjected with a gamma-aminobutyric acid (GABA) agonist, muscimol, in the interposed nuclei, and the effects of inactivation of the intermediate cerebellar output on the forelimb reflexes were examined. The main findings of these experiments are that unilateral muscimol inactivation of the interposed nuclei in the cat abolished the expression of the classically conditioned limb flexion reflex, suppressed the performance of the unconditioned withdrawal reflex and, in parallel, down-regulated the tactile placing, hopping and magnet postural responses in the ipsilateral forelimb. These observations are inconsistent with concepts indicating exclusive involvement of the intermediate cerebellum in the classically conditioned reflexes elicited by aversive stimuli. On the contrary, they support the hypothesis of a more global involvement of this structure in learned and unlearned defensive flexion reflexes and in automatic postural response systems.

Animals↗

A second forelimb motor area exists in rat frontal cortex.

Intracortical microstimulation of 40--50 points in the frontal cortex of ketamine-anesthetized rats using perpendicular penetrations has demonstrated a second forelimb area located rostrally near the frontal pole as well as confirming the existence of a more caudally located forelimb area just anterior to bregma. Cortex where neck and/or vibrissae movements were evoked separated the two forelimb areas. The rostral and caudal forelimb areas defined by microstimulation correspond with patches of corticospinal neurons labeled with HRP following injections of this tracer into the cervical enlargement. Digit movements were commonly evoked from the rostral forelimb area but were rarely elicited from the caudal forelimb area. The question of whether the rostral forelimb region is part of primary or supplementary motor cortex is not yet able to be answered.

Animals↗

Role of joint afferents in relation to the initiation of forelimb stepping in thalamic cats.

To analyze the roles of joint afferents in relation to initiation of forelimb stepping in thalamic cats, we recorded the unit spikes of the cervical dorsal roots, stimulated the joint afferents, and applied local anesthesia to the joint capsule. Almost all of the joint afferents of the shoulder, elbow, wrist and finger adapted slowly and exhibited alternating firing during forelimb stepping. About 45% of the afferents of each joint showed firings as the limb moved from forward to backward. About 44% of the afferents exhibited discharges as the limb moved from backward to forward. The remaining afferents showed firings as the limb moved in both directions. The application of local anesthesia to joints of the shoulder, elbow or wrist resulted in a marked reduction of forelimb stepping. Forelimb stepping was evoked by electric stimulation of the joint capsule, when excitabilities of flexor motoneurons were increased due to muscle stretching. Impulses originating in the joint afferents of the forelimb entered the spinal cord and ascended to the dorsolateral funiculus of the cervical cord, since forelimb stepping was abolished after bilateral transection of this part. Our results indicate that joint afferents may play an important role in the initiation of forelimb stepping in thalamic cats walking on a motor-driven treadmill.

Afferent Pathways↗

Crossed forelimb extension produced in thalamic cats by injection of putative transmitter substances into the paralemniscal pontine reticular formation.

To analyze the descending pathways of the paralemniscal pontine reticular formation (PLRF), a technique was used for the selective activation of cell bodies by localized injection of putative neurotransmitters in the PLRF. When a small amount (less than 0.1 microliter) of 0.1 M glutamate was injected into the PLRF unilaterally in thalamic cats, the forelimb contralateral (c-forelimb) to the injection was extended, and occasionally the ipsilateral forelimb was flexed. These responses were similar to those obtained by electrical stimulation of the PLRF, but were relatively weaker. Unit spikes of PLRF neurons were increased in frequency following administration of glutamate. The latent periods and durations of increases in spike frequency varied depending on the concentration and quantity of the glutamate solution, and were roughly similar to those of the extensor EMG in the c-forelimb. Since the firing of PLRF neurons preceded the EMG with 11 ms latency, the unit spike of PLRF neurons could be used as a triggering signal to observe a spike triggered averaged EMG response in the extensor muscle of the c-forelimb. Results similar to those with glutamate were observed upon administration of quisqualate, kainate and aspartate. The most effective compound was quisqualate. Application to the PLRF of 1-naphthylacetyl spermine (1-NA-Spm), an analogue of the natural spider toxin JSTX-3 and an antagonist of glutamate, suppressed both the PLRF neuron activity and the extensor EMG of the c-forelimb. These observations suggest that extensor muscles of the forelimb are excited by the contralateral PLRF, perhaps via the crossed reticulospinal tract from the PLRF. PLRF neurons may be activated by glutamate (quisqualate) receptors.

Animals↗

Reaching behavior in the rat: absence of forelimb peripheral input.

In order to test whether peripheral input from a moving forelimb is essential for reaching in rats, the effects of dorsal rhizotomy C5-Th2 were examined. Rats were trained to reach for a food pellet in the horizontal tube or on a tray. Reaching attempts before and after bilateral forelimb deafferentation were monitored by continual recording using magnetic induction. Deafferented animals were able to initiate and generate the motor program of reaching, but modulation of its ongoing execution was lost. Peripheral input from moving forelimb was necessary for the effective performance of grasping; the duration of the manipulative part of reaching was significantly prolonged and the success of grasping was markedly decreased. Also, the aiming of forelimb was impaired, probably by disturbing of body forelimb postural coordination. No significant changes were found in the execution of forelimb protraction. It is concluded that somesthetic feedback is not required for execution of forelimb protraction, but it is necessary for grasping.

Animals↗

Quantitative assessment of forelimb motor function after cervical spinal cord injury in rats: relationship to the corticospinal tract.

Approximately 50% of human spinal cord injuries (SCI) are at the cervical level, resulting in impairments in motor function of the upper extremity. Even modest recovery of upper extremity function could have an enormous impact on quality of life for quadriplegics. Thus, there is a critical need to develop experimental models for cervical SCI and techniques to assess deficits and recovery of forelimb motor function. Here, we analyze forelimb and forepaw motor function in rats after a lateral hemisection at C5 and assessed the relationship between the functional impairments and the extent of damage to one descending motor system, the corticospinal tract (CST). Female Sprague-Dawley rats were trained on various behavioral tasks that require the forelimb, including a task that measures gripping ability by the hand (as measured by a grip strength meter, GSM), a food reaching task, and horizontal rope walking. After 8 weeks of post-injury testing, the distribution of the CST was evaluated by injecting BDA into the sensorimotor cortex either ipsi- or contralateral to the cervical lesion. Complete unilateral hemisection injuries eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion. There was no indication of recovery in either task. In cases in which hemisections spared white matter near the midline, there was some recovery of forelimb motor function over time. Assessment of rope climbing ability revealed permanent impairments in forelimb use and deficits in hindlimb use and trunk stability. Sensory testing using a dynamic plantar aesthesiometer revealed that there was no increase in touch sensitivity in the affected forelimb. For the cases in which both histological and behavioral data were available, spared forelimb motor function was greatest in rats in which there was sparing of the dorsal CST.

Animals↗

Topographical organization of projections to cat motor cortex from nucleus interpositus anterior and forelimb skin.

1. The activation of the motor cortex from focal electrical stimulation of sites in the forelimb area of cerebellar nucleus interpositus anterior (NIA) was investigated in barbiturate-anaesthetized cats. Using a microelectrode, nuclear sites were identified by the cutaneous climbing fibre receptive fields of their afferent Purkinje cells. These cutaneous receptive fields can be identified by positive field potentials reflecting inhibition from Purkinje cells activated on natural stimulation of the skin. Thereafter, the sites were microstimulated and the evoked responses were systematically recorded over the cortical surface with a ball-tipped electrode. The topographical organization in the motor cortex of responses evoked by electrical stimulation of the forelimb skin was also analysed. 2. Generally, sites in the forelimb area of NIA projected to the lateral part of the anterior sigmoid gyrus (ASG). Sites in the hindlimb area of NIA also projected to lateral ASG and in addition to a more medial region. Sites in the face area of NIA, however, projected mainly to the middle part of the posterior sigmoid gyrus (PSG). 3. For sites in the forelimb area of NIA, the topographical organization and strength of the projections varied specifically with the cutaneous climbing fibre receptive field of the site. The largest cortical responses were evoked from sites with receptive fields on the distal or ventral skin of the forelimb. 4. Microelectrode recordings in the depth of the motor cortex revealed that responses evoked by cerebellar nuclear stimulation were due to an excitatory process in layer III. 5. Short latency surface responses evoked from the forelimb skin were found in the caudolateral part of the motor cortex. At gradually longer latencies, responses appeared in sequentially more rostromedial parts of the motor cortex. Since the responses displayed several temporal peaks that appeared in specific cortical regions for different areas of the forelimb skin, several somatotopic maps were seen. 6. The cerebellar and cutaneous projections activated mainly different cortical regions and had topographical organizations that apparently were constant between animals. Their patterns of activation may constitute a frame of reference for investigations of the functional organization of the motor cortex.

Afferent Pathways↗

Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats.

In adult rats that sustained forelimb amputation on the day of birth, >30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA(A+B) receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimb-stump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in approximately 60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats.

Action Potentials↗

Blockade of GABAergic inhibition reveals reordered cortical somatotopic maps in rats that sustained neonatal forelimb removal.

A previous study from this laboratory demonstrated that forelimb removal at birth results in invasion of the cuneate nucleus (CN) by sciatic nerve axons and the development of CN cells including thalamic projection neurons with receptive fields that include both the forelimb stump and the hindlimb. However, recordings from unit clusters in lamina IV of the primary somatosensory cortex (SI) of these animals revealed the presence of only a very few sites in the forelimb stump representation where responses to hindlimb stimulation could also be recorded. In the present study we tested the possibility that input from the hindlimb was suppressed in lamina IV of the cortical stump representation via GABAergic inhibitory mechanisms by mapping this cortical region, applying the gamma-aminobutyric acid-A (GABA(A)) and GABA(B) receptor antagonists bicuculline and phaclofen (50 microM each), and then remapping the same sites. In six neonatally manipulated rats, 15 of 242 sites (6.2%) in the stump representation responded to hindlimb stimulation before GABA receptor blockade and 107 (44.2%) of the same sites responded to stimulation of the hindlimb during blockade (P < 0.05). In six normal adult rats, 7 of 264 sites (2.7%) in the forelimb representation responded to hindlimb stimulation before the application of bicuculline and phaclofen. During GABA receptor blockage, 31 of these sites (11.7%) responded to such stimulation (P < 0.02 vs. the untreated normal cortex and P < 0.01 vs. the neonatally manipulated rats treated with GABA blockers). To specifically test the role of GABA(A) versus GABA(B) receptors in the inhibition of hindlimb input to the SI stump representation in rats that sustained neonatal forelimb removal, either bicuculline or phaclofen alone was applied to SI in nine neonatally manipulated animals. In four rats treated with bicuculline, 12 of 184 sites (6.5%) in the stump representation responded to hindlimb stimulation before treatment and 61 of 184 sites (33.2%) responded to such stimulation during application (P < 0.01). In animals (n = 5) treated with phaclofen, 18 of 251 sites (7.2%) responded to hindlimb stimulation before treatment and 64 of these sites (25.5%) responded to such stimulation during application (P < 0.05). There was no significant difference between the results obtained with bicuculline alone, phaclofen alone, or the two GABA blockers delivered together (P > 0.05). These results indicate that hindlimb input to the portion of SI representing the forelimb stump is functionally suppressed in rats that have sustained neonatal forelimb removal and that GABAergic inhibition, mediated by both GABA(A) and GABA(B) receptors, is involved in this process.

Afferent Pathways↗

Anti-inflammatory actions of enprofylline, a modified xanthine, in the canine forelimb.

It has been previously reported that enprofylline (3-propyl xanthine) prevents histamine-mediated edema formation in the guinea pig lung. To further assess the potential anti-inflammatory effects of enprofylline, we infused it intra-arterially into the canine forelimb before and during a local intra-arterial infusion of histamine (4 micrograms/min) while monitoring forelimb skin lymph parameters. Infusion of enprofylline at 2 mg/min significantly decreased forelimb arterial pressures and increased heart rate and pulse pressure. Subsequent infusion of histamine caused a further reduction in forelimb arterial pressures and an increase in lymph flow, protein concentration, and protein transport similar to that seen with the infusion of histamine alone. Infusion of enprofylline at 5 mg/min decreased forelimb arterial pressures and systemic pressure. Subsequent histamine infusion further reduced forelimb arterial pressures, but the increase in lymph parameters was markedly attenuated. Enprofylline infused at 10 mg/min also decreased forelimb arterial and systemic pressures, but subsequent histamine infusion was essentially without effect on lymph parameters. To assess the role of catecholamines in enprofylline-mediated attenuation of histamine edema formation, we infused enprofylline at 5 mg/min in the presence of a beta 2-receptor blockade produced by the intra-arterial infusion of ICI 118551. The effects of enprofylline and histamine on vascular pressures were similar to those seen in the absence of beta 2-receptor blockade, but lymph flow, protein concentration, and protein transport increased similar to that seen with histamine alone. These data indicate that enprofylline is capable of attenuating histamine-induced increases in microvascular permeability, but this action of enprofylline is of an indirect nature, mediated through the release of catecholamines.

Adrenergic beta-Agonists↗

Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat.

Improving functional recovery following cerebral strokes in humans will likely involve augmenting brain plasticity. This study examined skilled forelimb behavior, neocortical evoked potentials, and movement thresholds to assess cortical electrical stimulation concurrent with rehabilitative forelimb usage following a focal ischemic insult. Adult rats were trained on a task that required skilled usage of both forelimbs. They then underwent an acute focal ischemic insult to the caudal forelimb area of sensorimotor cortex contralateral to their preferred forelimb. During the same procedure, they also received a stimulation electrode over the infarct area and two depth electrodes anterior to the lesion to record evoked potentials. One week following the surgery, rats received cortical stimulation during performance of the skilled task. Evoked potentials and movement thresholds were also determined. Functional assessment revealed that cortical stimulation resulted in superior performance compared to the no stimulation group, and this was initially due to a shift in forelimb preference. Cortical stimulation also resulted in enhanced evoked potentials and a reduction in the amount of current required to elicit a movement, in a stimulation frequency dependent manner. This study suggests that cortical stimulation, concurrent with rehabilitative training, results in better forelimb usage that may be due to augmented synaptic plasticity.

Analysis of Variance↗

Diffusion of mepivacaine between adjacent synovial structures in the horse. Part 1: forelimb foot and carpus.

This paper tests the hypothesis that the local analgesic agent mepivacaine diffuses between adjacent equine synovial structures in the forelimb and with greater frequency than latex, gelatine dye or contrast media. We report the incidence of diffusion of mepivacaine between the distal interphalangeal joint (DIPJ) and navicular bursa (NB) of the forelimbs and between the intercarpal (IC) and radiocarpal (RC) joints of 31 fresh equine cadavers. The DIPJ of one forelimb and the NB of the contra lateral forelimb and the RC joint of one forelimb and the IC joint of the contra lateral forelimb were injected with mepivacaine. After flexion and extension of the joints, synovial fluid was obtained from the synovial structures adjacent to the injected synovial structures. The concentration of mepivacaine in these samples was determined using an enzyme linked immunosorbent assay. For samples obtained by dilution of synovial fluid, the concentration of mepivacaine was determined by comparing the concentrations of urea in the diluted synovial fluid and the concentration of serum urea. Mepivacaine diffused from the DIPJ to the NB or from the NB to the DIPJ in 25/25 (100%) limbs. Mepivacaine diffused from the IC to RC joints in 24/25 (96%) limbs and from the RC to IC joints in 21/25 (84%) limbs. It was detected at concentrations >0.3 mg/l in 9/25 (36%) of IC joints after RC joint injection and in 25/25 (100%) of the NB after DIPJ injection; at concentrations >100 mg/l in 2/25 (8%) of IC and RC joints and 12/25 (48%) of NB following DIPJ injection; and at concentrations >300 mg/l in 1/25 (4%) in the IC joints following RC joint injection and in 11/25 (44%) of DIPJ following NB injection. The results show greater diffusion of mepivacaine between adjacent synovial structures than assumed from previous anatomical, latex injection and contrast arthrographic studies. This study showed that commonly performed intrasynovial analgesic techniques in the forelimb of the horse are not as specific as previously reported.

Anesthetics, Local↗

Modulation of sustained electromyographic activity by single intracortical microstimuli: comparison of two forelimb motor cortical areas of the rat.

In rats, a rostral and a caudal forelimb motor area (RFA and CFA, respectively) have been distinguished on the basis of intracortical microstimulation effects (see Neafsey et al., 1986, for a review). The goal of the present study was to assess and compare their relative connectional strength with target motor units of the forelimb. This was achieved by averaging modulation responses of sustained electromyographic (EMG) activity triggered by single intracortical microstimuli (S-ICMS) of relatively low intensity (mostly below 35 microA) to minimize both direct and transsynaptic current spread. In chronically prepared and ketamine-sedated rats, this method produced prominent peaks and troughs in the averaged EMG at short latencies with S-ICMS currents as low as 5 microA. S-ICMS at 30-50 microA in CFA sometimes even elicited visible twitches and an EMG burst of the contralateral wrist or digits following each stimulation pulse. Increasing S-ICMS currents to about 1.5 mA revealed a sudden shortening of EMG response latencies, which was most likely induced by current spread to brainstem motor centers. S-ICMS at near-threshold intensity in the majority of effective sites in both CFA and RFA produced modulation responses in more than one group of forelimb muscles, frequently also including muscles of the ipsilateral forelimb. Usually the ipsilateral responses were weaker, as were the suppression effects. Comparison of CFA and RFA revealed similar effects in terms of the number of modulated muscle groups and the response latencies. In contralateral wrist/digit muscles, facilitation responses were elicited at latencies of 9.7 +/- 1.8 msec (CFA) and 9.6 +/- 1.9 msec (RFA), with the shortest latencies around 6 msec. However, modulations by S-ICMS in RFA had significantly smaller amplitudes, had slower rates of buildup, and required higher thresholds than those obtained from S-ICMS in CFA. It is concluded, on the basis of the S-ICMS method, that both the CFA and the RFA exert a prominent and relatively direct influence on forelimb motoneurons. The present findings, together with calculations of conduction time, suggest that a contingent of corticospinal axons of the rat has oligosynaptic and possibly even monosynaptic connections with forelimb motoneurons. The recruitment of a relatively large number of muscles, including those of the ipsilateral forelimb, by S-ICMS in both areas may be explained by the prominent divergence of corticospinal axons. Further investigations are required to understand the relative positions and roles of the two areas in motor control and their possible homology with primary and nonprimary motor areas of primates.

Animals↗

Unilateral sensorimotor cortex lesions in adult rats facilitate motor skill learning with the "unaffected" forelimb and training-induced dendritic structural plasticity in the motor cortex.

In humans and other animals, sufficient unilateral damage to the sensorimotor cortex can cause impairments in the opposite forelimb and the development of a hyper-reliance on the nonimpaired limb. This hyper-reliance is adaptive to the extent that it contributes to functional compensation for lesion-induced impairments. We have found that unilateral lesions of the forelimb region of the sensorimotor cortex (FLsmc) in rats, or callosal transections, cause neurons of the opposite motor cortex to become exceptionally responsive to changes in forelimb behavior. This enhanced responsiveness might facilitate learning of compensatory strategies with the nonimpaired forelimb after unilateral FLsmc lesions. The possibility that these lesions facilitate learning with the nonimpaired forelimb was addressed in this study. Rats were required to learn a skilled forelimb reaching task after either unilateral FLsmc lesions or sham operations. The trained limb in animals with lesions was the nonimpaired limb. Compared with shams, rats with unilateral lesions had a greater rate of acquisition and asymptotic performance level on the task, which was especially evident on more difficult trials. Quantitative measures of microtubule associated protein-2 (MAP2) immunostained dendrites indicated an enhancement of training-induced dendritic cytoskeletal changes in the motor cortex opposite lesions. Thus, unilateral FLsmc lesions facilitate learning of at least some types of motor skills using the nonimpaired forelimb as well as some of the neuronal changes associated with this learning. This facilitation could be a substrate underlying behavioral compensation for unilateral FLsmc damage and may contribute to the phenomenon of learned nonuse of the impaired limb.

Adaptation, Physiological↗

Effects of histamine-receptor agonists on transvascular fluid and macromolecular efflux in the canine forelimb.

Histamine increases transvascular fluid and protein efflux in the canine forelimb resulting in edema formation. To clarify the receptor mechanisms of histamine edema, we infused H1 and H2-receptor agonists into the forelimb perfused at constant flow while measuring skin lymph parameters or forelimb weight. The H1-receptor agonist 2(2-pyridyl) ethylamine [PEA] or the H2-receptor agonist 4-methyl histamine (8-40 micrograms/min) singly or in combination fails to increase lymph flow, protein concentration or protein transport. PEA in a dose of 80-400 micrograms/min increases lymph flow, protein concentration and protein transport. 4-Methyl histamine in a dose of 40-200 micrograms/min produces a small but significant decrease in lymph flow and protein transport subsequent to a fall in systemic pressure. 4-Methyl histamine at 40 and 80 micrograms/min produces a progressive and sustained increase in forelimb weight PEA at 40 micrograms/min produces a small increase in forelimb weight which quickly plateaus much like the response seen with acetylcholine (10 micrograms base/min). However, infusion of PEA at 80 micrograms/min progressively increases forelimb weight, similar to that seen with 4-methyl histamine or histamine (1.4 microgram base/min). These data indicate that either H1 or H2-receptor agonists can cause edema formation in the canine forelimb, and imply that histamine edema involves both H1 and H2-receptor interaction.

Animals↗

Mechanism of forelimb skin and skeletal muscle glucose uptake during Escherichia coli endotoxin shock in the dog.

This study was undertaken to investigate mechanisms of increased glucose uptake by forelimb skin and skeletal muscle during endotoxin shock. Anesthetized mongrel dogs were used. Forelimbs were perfused at either natural or constant blood flow. Temperature of the isolated forelimb was maintained at core temperature. Shock was induced by an IV injection of 2 mg/kg Escherichia coli endotoxin. Forelimb skin and skeletal muscle glucose uptake increased by 30 minutes of shock and remained elevated in the natural flow study. In the constant flow study, glucose uptake by both skin and skeletal muscle was increased at 30 minutes of shock but thereafter returned to control. The natural flow forelimbs were ischemic and hypoxic during shock, whereas the constant flow forelimbs were neither ischemic not hypoxic. Progressive hypoglycemia developed in both endotoxin shock groups. These data support the hypothesis that the mechanism of increases in forelimb skin and skeletal muscle glucose uptake during endotoxin shock is related to local tissue hypoxia.

Animals↗

Forelimb segment length proportions in extant hominoids and Australopithecus afarensis.

Forelimb proportions have been used to infer locomotor adaptation in Australopithecus afarensis. However, little is known about proportions among individual forelimb segments in extant or fossil hominoids. The partial A. afarensis skeleton A.L. 438-1 and the more complete skeleton A.L. 288-1 provide the opportunity to assess relative length of the arm, forearm, wrist, and palm. We compare scaling relationships between pairs of forelimb bones of extant hominoids and A. afarensis, and length of individual forelimb elements to a body size surrogate. Hylobatids, and to a lesser extent orangutans, have the longest forelimb bones relative to size, although the carpus varies little among taxa, perhaps due to functional constraints of the wrist. Pan species are unique in having long metacarpals relative to ulnar length, demonstrating that they probably differ from the common chimp-human ancestor, and also that developmental mechanisms can be altered to results in differential growth of individual forelimb segments. A. afarensis has no forelimb bones that are significantly longer than those of humans for its size. It falls within the range of variation seen in modern humans for all comparisons relative to size, but appears to differ from the typical human brachial index due to a slightly shorter humerus and/or slightly longer ulna. It has short metacarpals like humans only among hominoids. Thus, while Pan may have elongated its metacarpus relative to ulnar length, A. afarensis may have reduced the length of its metacarpals and possibly its humerus relative to body size from the primitive condition.

Adaptation, Physiological↗