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PubMed1999

Increased hindlimb leukocyte concentration in a chronic rodent model of venous hypertension.

BACKGROUND: The pathophysiologic mechanism for tissue damage in chronic venous insufficiency (CVI) is venous hypertension (VH), the primary mediator behind leukocyte trapping in tissues. We developed a new rodent model of chronic hindlimb VH to allow testing of the microvascular dysfunction that occurs in clinical CVI. MATERIALS AND METHODS: Hindlimb VH was created in adult rats ( approximately 350 g, male, Wistar) by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In a sham group, a loose tie was placed around the same vessels. One week later, pressure catheters were placed in the right common carotid artery, right internal jugular vein (forelimb), and right superficial epigastric vein (hindlimb). Measurements were taken 15 min later, to allow for stabilization. Bilateral forelimb and hindlimb skin specimens were harvested. The myeloperoxidase (MPO) assay, an indicator of tissue leukocyte trapping, was performed using a well-described, standard technique. RESULTS: In the chronic rats (n = 8), the hindlimb pressures (12.6 +/- 3.2 mm Hg) were significantly elevated (P < 0.05) when compared to forelimb pressures (1.75 +/- 0.71) and to chronic sham rat (n = 6) hindlimb (3.3 +/- 1.2) pressures. There was a significant (P < 0.05) elevation of MPO activity in hindlimbs of the chronic group (32.9 +/- 13.9 units) when compared to forelimbs (17 +/- 11.3) and sham hindlimbs (18 +/- 10.2). CONCLUSIONS: In our chronic model, as in clinical studies and previous acute investigations, we have demonstrated, using an MPO assay, an increase in the amount of cutaneous leukocytes in the hindlimbs with chronic VH but not in experimental forelimbs or sham hindlimbs or forelimbs.

Animals↗
PubMed2002

Medullary reticulospinal tract mediating the generalized motor inhibition in cats: II. Functional organization within the medullary reticular formation with respect to postsynaptic inhibition of forelimb and hindlimb motoneurons.

We compared postsynaptic inhibitory effects on forelimb motoneurons and those on hindlimb motoneurons during generalized motor inhibition evoked by stimulating the medullary reticular formation in decerebrate cats. Here, we address two questions. First, whether the medullary inhibitory effects upon forelimb motoneurons are equivalent to those upon hindlimb motoneurons. Second, whether there is a somatotopographical organization within the medullary reticular formation in terms of inhibitory connections with motoneurons. Repetitive stimulation (20-50 microA, 50-100 Hz) delivered to the dorsomedial medullary reticular formation bilaterally suppressed muscle tone of both the forelimbs and hindlimbs. The medullary stimulation hyperpolarized the membrane potentials of the forelimb (5.4+/-1.8 mV, n=46) and hindlimb (5.4+/-2.0 mV, n=59) motoneurons together with a decrease in input resistance. The degree of membrane hyperpolarization and input resistance was not different in the forelimb and hindlimb motoneurons. The medullary stimulation also depressed the capability of generating antidromic and orthodromic spikes in the motoneurons. Stimuli with pulse trains (one to three pulses, 5-10-ms intervals, 20-50 microA) applied to the medullary inhibitory region induced a mixture of excitatory and inhibitory postsynaptic potentials in the motoneurons. The most noteworthy potentials were the inhibitory postsynaptic potentials with a late latency. They were observed in most forelimb (n=57/58, 98.3%) and hindlimb (n=63/64, 98.4%) motoneurons. The inhibitory potentials in forelimb motoneurons had a latency of 25-30 ms and a peak latency of 35-40 ms, and those in hindlimb motoneurons had a latency of 30-35 ms and a peak latency of 50-60 ms. A difference was not observed in the location of the effective sites for evoking the inhibitory effects in the forelimb and hindlimb motoneurons. These sites were homogeneously distributed in the dorsomedial part of the medullary reticular formation corresponding to the location of the nucleus reticularis gigantocellularis. From these findings we suggest that there is an equivalent amount of the postsynaptic inhibitory effects exerted on forelimb and hindlimb motoneurons during medullary-induced generalized motor inhibition. In addition, the medullary reticular formation may be functionally organized as a homogeneous or non-specific region in terms of the medullary reticulospinal inhibitory connections with forelimb and hindlimb motoneurons.

Animals↗
PubMed1993

Evaluation of the arteriovenous difference technique to simultaneously estimate protein synthesis and degradation in the hindlimb of fed and chronically underfed steers.

Our objectives were to validate a technique to measure protein turnover based on net fluxes of tyrosine radioactivity and mass across the hindlimb, and to describe the impact of nutrition on hindlimb protein kinetics and nutrient utilization in growing Holstein steers. External iliac vessels were catheterized to allow for measurements of hindlimb arteriovenous (AV) differences and blood flow. Animals were used in a single reversal design with 16-d periods. Treatments were either 60% (0.6M) or 220% (2.2M) of the energy required for maintenance. On d 12 and 14 of each period, a primed-continuous infusion of L-[side chain-2,3-3H]tyrosine was initiated, followed by a 4-h sampling period to assess hindlimb nutrient utilization and protein kinetics. Well-fed steers exhibited rates of hindlimb utilization for non-nitrogenous energy substrates and amino acids that were consistent with values previously reported for well-fed ruminants. Underfeeding decreased hindlimb blood flow (62%), oxygen consumption (51%) and utilization of respiratory fuels (64-73%). Protein synthesis was also reduced (49%), leading to net nitrogen loss from the hindlimb. The estimated energy cost of protein synthesis accounted for 13% of hindlimb oxygen consumption across intake levels. Hindlimb protein balance was consistent with whole-body balance, adding credence to derived rates of degradation. Overall, data support the validity of the AV difference technique to estimate components of hindlimb protein turnover.

Animals↗
PubMed2000

Analysis of the hemodynamic effects of heparinase I and protamine sulfate in the systemic and hindlimb vascular beds of the male rat.

The effects of heparinase I and protamine sulfate on the mean arterial pressure and hindlimb perfusion pressure in the male rat were studied. With institutional approval, 21 male Sprague-Dawley rats were anesthetized, and the carotid artery and abdominal aorta were cannulated by cutdown. To isolate the hindlimb, a semi-closed peristaltic perfusion circuit was used. Heparinase I or protamine sulfate was injected into the hindlimb vascular bed, and changes in mean arterial pressure and hindlimb perfusion pressure were recorded. Analysis of variance with a post hoc Scheffe's test was used for statistical analysis, and a P value less than.05 was considered significant. Increasing doses of heparinase I caused a small but significant decrease in mean arterial pressure only at the two highest doses. At all doses, hindlimb perfusion pressure was significantly less than the baseline value and than the value with saline administration at 1 minute. At the clinically applicable doses of heparinase I (0.625 and 1.25 IU/kg), the decrease in hindlimb perfusion pressure was less than 7. At the next two higher doses, the change was less than 15%. The vehicle of heparinase caused a significant decrease in mean arterial pressure (from -15% to -30%) and hindlimb perfusion pressure (from -10% to -20%). Increasing doses of protamine sulfate caused an increase in hindlimb perfusion pressure from baseline, including a 58% change with the 10-mg/kg dose. There was a transient decrease in mean arterial pressure, which peaked 4 to 5 minutes after injection, to a 21% decrease from baseline with the 5- and 10-mg/kg doses. Heparinase I caused vasodilation in the hindlimb and decreased mean arterial pressure only at supraclinical doses. Protamine sulfate caused a significant dose-dependent increase in hindlimb vascular resistance and a transitory decrease in mean arterial pressure.

Animals↗
PubMed2004

Local GABA receptor blockade reveals hindlimb responses in the SI forelimb-stump representation of neonatally amputated rats.

In adult rats that sustained forelimb amputation on the day of birth, there are numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to cutaneous stimulation of the hindlimb when cortical receptors for GABA are blocked. These normally suppressed hindlimb inputs originate in the SI hindlimb representation and synapse in the dysgranular cortex before exciting SI forelimb-stump neurons. In our previous studies, GABA (A + B) receptor blockade was achieved by topically applying a bicuculline methiodide/saclofen solution (BMI/SAC) to the cortical surface. This treatment blocks receptors throughout SI and does not allow determination of where along the above circuit the GABA-mediated suppression of hindlimb information occurs. In this study, focal injections of BMI/SAC were delivered to three distinct cortical regions that are involved in the hindlimb-to-forelimb-stump pathway. Blocking GABA receptors in the SI hindlimb representation and in the dysgranular cortex was largely ineffective in revealing hindlimb inputs ( approximately 10% of hindlimb inputs were revealed in both cases). In contrast, when the blockade was targeted at forelimb-stump recording sites, >80% of hindlimb inputs were revealed. Thus GABAergic interneurons within the forelimb-stump representation suppress the expression of reorganized hindlimb inputs to the region. A circuit model incorporating these and previous observations is presented and discussed.

Amputation Stumps↗
PubMed2005

Testing the hindlimb-strength hypothesis: non-aerial locomotion by Chiroptera is not constrained by the dimensions of the femur or tibia.

In the evolution of flight bats appear to have suffered a trade-off; they have become poor crawlers relative to terrestrial mammals. Capable walking does occur in a few disparate taxa, including the vampire bats, but the vast majority of bats are able only to shuffle awkwardly along the ground, and the morphological bases of differences in crawling ability are not currently understood. One widely cited hypothesis suggests that the femora of most bats are too weak to withstand the compressive forces that occur during terrestrial locomotion, and that the vampire bats can walk because they possess more robust hindlimb skeletons. We tested a prediction of the hindlimb-strength hypothesis: that during locomotion, the forces produced by the hindlimbs of vampire bats should be larger than those produced by the legs of poorly crawling bats. Using force plates we compared the hindlimb forces produced by two species of vampire bats that walk well, Desmodus rotundus (N=8) and Diaemus youngi (N=2), to the hindlimb forces produced during over-ground shuffling by a similarly sized bat that is a poor walker (Pteronotus parnellii; N=6). Peak hindlimb forces produced by P. parnellii were larger (ANOVA; P<0.05; N=65) and more variable (93.5+/-36.6% body weight, mean +/- s.d.) than those of D. rotundus (69.3+/-8.1%) or D. youngi (75.0+/-6.2%). Interestingly, the vertical components of peak force were equivalent among species (P>0.6), indicating similar roles for support of body weight by the hindlimbs in the three species. We also used a simple engineering model of bending stress to evaluate the support capabilities of the hindlimb skeleton from the dimensions of 113 museum specimens in 50 species. We found that the hindlimb bones of vampires are not built to withstand larger forces than those of species that crawl poorly. Our results show that the legs of poorly crawling bats should be able to withstand the forces produced during coordinated crawling of the type used by the agile vampires, and this indicates that some mechanism other than hindlimb bone thickness, such as myology of the pectoral girdle, limits the ability of most bats to crawl.

Analysis of Variance↗
PubMed1990

Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: functional aspects.

Following heterotopic transplantation of the thoracic neural tube to the lumbar region on embryonic day (E) 2, the transplanted cord differentiates normally and establishes neuroanatomical connections with the host central nervous system and hindlimb muscles. Beginning on about E12, however, the neuromuscular system begins to undergo regressive changes resulting in motoneuron degeneration and muscle atrophy (O'Brien and Oppenheim, 1990). In the present paper, we have examined the development of neuromuscular function in thoracic transplant embryos from E6 to the time of hatching on E20-21. The onset of hindlimb movements and reflexes occurred at the same time (E6-E8) in both control and thoracic transplant embryos. Further, both the nature (pattern) and frequency of these movements appeared normal in the thoracic transplants up to E10-E12, after which there was a gradual and marked reduction in the frequency, and an alteration in the pattern, of both spontaneous and reflex-evoked hindlimb movements. After E16 normal movements were virtually absent in many of the thoracic transplant cases. By contrast, movements of the head, trunk and wings were normal in these embryos throughout the observation period. Hindlimbs innervated partly by the thoracic transplant and partly by remaining host lumbar cord did not exhibit the regressive changes in function after E10 that occurred in hindlimbs innervated exclusively by the thoracic transplant. EMG recordings from specific hindlimb muscles innervated solely by thoracic motoneurons demonstrated that the activation pattern of both flexors and extensors was similar to the repetitive pattern observed in normal thoracically innervated intercostal muscles (i.e., extensor-like). Muscles did not show distinguishable EMG burst patterns with inhibitory periods as do control lumbar innervated muscles. We conclude that the development of the pattern generating circuitry in the transplanted thoracic cord was similar to normal thoracic cord and thus appeared to be uninfluenced by having contacted the foreign hindlimb muscle targets early in development. Activity blockade with curare from E6 to E14 suppressed the loss of motoneurons that occurs in the thoracic transplant after E10. Thus, the abnormal thoracic-like activation pattern of thoracically innervated hindlimbs may be a critical signal in the initiation of the neuromuscular regression that occurs after E10 in these preparations. Finally, although the innervation and formation of neuromuscular endplates in thoracic transplants appeared normal up to E12, by E14 both the intramuscular nerves and the endplates exhibited signs of degeneration and regression. Thoracic motoneurons are initially able to innervate and functionally activate hindlimb muscles in a manner similar to that of thoracically innervated intercostal muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Geometry of blood-tissue exchange in bat flight muscle compared with bat hindlimb and rat soleus muscle.

We investigated the relationship between capillary-to-fiber geometry and muscle aerobic capacity by comparing the bat flight muscle (pectoralis muscle), i.e., an ultimate case of extreme O2 demand in a mammalian skeletal muscle, with bat hindlimb and rat soleus muscles. At a given sarcomere length (2.1 microns), fiber cross-sectional area was considerably smaller in bat muscles (pectoralis 318 +/- 10 microns 2, hindlimb 447 +/- 35 microns 2) than in rat soleus muscle (2,027 +/- 125 microns 2). Capillary number per fiber cross-sectional area was much greater in bat pectoralis (6,394 +/- 380/mm2) than in bat hindlimb and rat soleus muscle (2,865 +/- 238 and 1,301 +/- 129/mm2, respectively; all values normalized to 2.1-microns sarcomere length). At the same sarcomere length (2.1 microns), the degree of tortuosity and branching of capillaries were significantly greater in bat pectoralis than in bat hindlimb and rat soleus muscle. In bat flight muscle, capillary length per fiber volume was very high (9,025 +/- 342/mm2). It was 2.2- and 5.4-fold larger than in bat hindlimb and rat soleus, respectively. Mitochondria occupied 35.3 +/- 1.2, 16.5 +/- 1.3, and 6.1 +/- 0.9% of the muscle fiber volume in bat pectoralis, hindlimb, and rat soleus muscles, respectively. There was a strong correlation between capillary length (as well as capillary surface) per fiber volume and mitochondrial volume density in all muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis, we found that 1) the number of capillaries around a fiber was linearly related to mitochondrial volume per micron length of fiber in the muscles but that 2) capillary surface per fiber surface, at given mitochondrial volume per micron length of fiber, was about twice as large in bat pectoralis as in rat soleus muscle, whereas in bat hindlimb it was intermediate between that in bat pectoralis and that in rat soleus muscle. This was due to the differences in fiber size (rat soleus greater than bat muscles) and capillary-to-fiber ratio (bat pectoralis greater than hindlimb) between the muscles. It is notable that in the bat, the substantially greater O2 transfer capacity of the flight muscle compared with hindlimb was achieved by increasing the size of the capillary-to-fiber interface, i.e., capillary-to-fiber surface, via an increase in capillary number rather than by substantially reducing fiber size.

Animals↗
PubMed1994

Motor cortical activity during voluntary gait modifications in the cat. II. Cells related to the hindlimbs.

1. To determine whether the motor cortex is involved in the modification of the hindlimb trajectory during voluntary adjustments of the locomotor cycle, we recorded the discharge patterns of 72 identified pyramidal tract neurons (PTNs) within the hindlimb region of pericruciate area 4 during a task in which cats stepped over obstacles attached to a moving treadmill belt. Data were also recorded from representative flexor and extensor muscles of the fore- and hindlimbs contralateral to the recording site. 2. To step over the obstacles, the cats increased flexion sequentially at the knee, ankle, and then the hip to bring the leg above and over the obstacle. This flexion movement was followed by a strong extension of the whole limb that repositioned the foot on the treadmill belt. These changes in limb trajectory were associated with large changes in the level of the activity of many flexor and extensor muscles of the hindlimb, and especially of the knee flexor, semitendinosus. On the basis of the time of onset of the knee and ankle extensor muscles in those steps when the limb was the first to be brought over the obstacle, the swing phase of the modified step cycle was subdivided into two parts, Phase I and Phase II, which correspond respectively to the flexion of the limb (F) and the initial extension (E1). 3. The temporal sequence of the movement was the same whether the hindlimb was the first (lead) or second (trail) to step over the obstacle, although the relative time between flexion at the three joints was changed in the two conditions. 4. Seventy-two PTNs were recorded from the posterior bank of the cruciate sulcus during the voluntary gait modifications. Sixty-three (63/72) of these PTNs had receptive fields that were confined to the contralateral hindlimb, or were recorded from penetrations in which such cells were found. Nine (9/72) PTNs had receptive fields on both the contralateral fore- and hindlimbs. Microstimulation applied through the recording electrode evoked, in all cases, brief twitch responses only in contralateral hindlimb musculature. 5. Forty-two (42/63) of those PTNs with receptive fields confined to the hindlimb showed a significant increase in their discharge frequency when the limb contralateral to the recording site was the first to step over the obstacle (lead limb). Twenty-nine PTNs (29/63) discharged maximally during the swing phase (18 in Phase I and 11 in Phase II), including two PTNS that also increased their discharge frequency during stance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Suppression of hindlimb inputs to S-I forelimb-stump representation of rats with neonatal forelimb removal: GABA receptor blockade and single-cell responses.

Neonatal forelimb removal in rats results in the development of inappropriate hindlimb inputs in the forelimb-stump representation of primary somatosensory cortex (S-I) that are revealed when GABA(A) and GABA(B) receptor activity are blocked. Experiments carried out to date have not made clear what information is being suppressed at the level of individual neurons. In this study, three potential ways in which GABA-mediated inhibition could suppress hindlimb expression in the S-I stump representation were evaluated: silencing S-I neurons with dual stump and hindlimb receptive fields, silencing neurons with receptive fields restricted to the hindlimb alone, and/or selective silencing of hindlimb inputs to neurons that normally express a stump receptive field only. These possibilities were tested using single-unit recording techniques to evaluate the receptive fields of S-I forelimb-stump neurons before, during, and after blockade of GABA receptors with bicuculline methiodide (for GABA(A)) and saclofen (for GABA(B)). Recordings were also made from normal rats for comparison. Of 92 neurons recorded from the S-I stump representation of neonatally amputated rats, only 2.2% had receptive fields that included the hindlimb prior to GABA receptor blockade. During GABA receptor blockade, 54.3% of these cells became responsive to the hindlimb, and in all but two cases, these same neurons also expressed a stump receptive field. Most of these cells (82.0%) expressed only stump receptive fields prior to GABA receptor blockade. In 71 neurons recorded from normal rats, only 5 became responsive to the hindlimb during GABA receptor blockade. GABA receptor blockade of cortical neurons, in both normal and neonatally amputated rats, resulted in significant enlargements of receptive fields as well as the emergence of receptive fields for neurons that were normally unresponsive. GABA receptor blockade also resulted in increases in both the spontaneous activity and response magnitudes of these neurons. These data support the conclusion that GABA mechanisms generally act to specifically suppress hindlimb inputs to S-I forelimb-stump neurons that normally express a receptive field on the forelimb stump only.

Amputation Stumps↗
PubMed2001

Intracortical pathway involving dysgranular cortex conveys hindlimb inputs to S-I forelimb-stump representation of neonatally amputated rats.

Reorganization of the primary somatosensory cortex (S-I) forelimb-stump representation of rats that sustained neonatal forelimb removal is characterized by the expression of hindlimb inputs that are revealed when cortical GABA receptors are pharmacologically blocked. Recent work has shown that the majority of these inputs are transmitted from the S-I hindlimb representation to the forelimb-stump field via an, as yet, unidentified pathway between these regions. In this study, we tested the possibility that hindlimb inputs to the S-I forelimb-stump representation of neonatally amputated rats are conveyed through an intracortical pathway between the S-I hindlimb and forelimb-stump representations that involves the intervening dysgranular cortex by transiently inactivating this area and evaluating the effect on hindlimb expression in the S-I forelimb-stump representation during GABA receptor blockade. Of 332 S-I forelimb-stump recording sites from six neonatally amputated rats, 68.3% expressed hindlimb inputs during GABA receptor blockade. Inactivation of dysgranular cortex with cobalt chloride (CoCl(2)) resulted in a significant decrease in the number of hindlimb responsive sites (9.5%, P < 0.001 vs. cortex during GABA receptor blockade before CoCl(2) treatment). Results were also compiled from S-I forelimb recording sites from three normal rats: 14.1% of 136 sites were responsive to the hindlimb during GABA receptor blockade, and all of these responses were abolished during inactivation of dysgranular cortex with CoCl(2) (P < 0.05). These results indicate that the S-I hindlimb representation transmits inputs to the forelimb-stump field of neonatally amputated rats through a polysynaptic intracortical pathway involving dysgranular cortex. Furthermore the findings from normal rats suggest that this pathway might reflect the amplification of a neuronal circuit normally present between the two representations.

Afferent Pathways↗
PubMed1984

Altered control of hindlimb vascular resistance by vagal afferents in spontaneously hypertensive rats. Difference in the early and late stage of hypertension.

The aim of this study was to examine whether control of vascular resistance by vagal afferents is altered in the early as well as late stage of hypertension. We examined the effects of vagotomy on hindlimb vascular resistance as well as on arterial baroreflex control of hindlimb vascular resistance in spontaneously hypertensive rats and Wistar-Kyoto rats, 12 and 35 weeks old. Vagotomy in rats with the intact arterial baroreceptors increased hindlimb vascular resistance in all four groups. Hindlimb vascular responses to graded sympathetic nerve stimulation were closely linear up to 6 Hz in all groups, and the slope of the response was approximately 1.4 times steeper in spontaneously hypertensive than in Wistar-Kyoto rats, in both the young and old groups. The increase in hindlimb vascular resistance after vagotomy normalized by the slope of the response to sympathetic nerve stimulation was greater in young spontaneously hypertensive rats than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive rats than in old Wistar-Kyoto rats. Vagotomy increased the gain of arterial baroreflex control of hindlimb vascular resistance in young spontaneously hypertensive rats, and in two groups of Wistar-Kyoto rats, but not in old spontaneously hypertensive rats. The percent increase in the gain of arterial baroreflex control of hindlimb vascular resistance after vagotomy tended to be greater in young spontaneously hypertensive than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. Central venous pressure and left ventricular end-diastolic pressure were higher in spontaneously hypertensive than in Wistar-Kyoto rats in both young and old groups. Left atrial distensibility assessed by obtaining the atrial pressure-volume relationship was comparable between young spontaneously hypertensive and young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. These results indicate that vagal afferents exert tonic inhibition on control of hindlimb vascular resistance in spontaneously hypertensive as well as in Wistar-Kyoto rats, and that tonic inhibitory influence of vagal afferents on control of hindlimb vascular resistance is altered in spontaneously hypertensive rats, augmented in young, but attenuated in old, spontaneously hypertensive rats, compared with that in age-matched Wistar-Kyoto rats. It is considered that altered control of vascular resistance by vagal afferents in spontaneously hypertensive rats may result from changes in vagal afferent activity.

Animals↗
PubMed1996

Characterization of dose-dependent metabolic responses to close arterial infusion of cimaterol in the hindlimb of steers.

Dose-dependent effects of cimaterol (CIM) on hindlimb metabolism were determined in six steers (247 +/- 22 kg BW) using a close arterial infusion. The external iliac vessels of both hindlimbs were catheterized to accommodate measurement of blood flow, circulating concentrations, and net flux of NEFA, lactate, and alpha-amino nitrogen (AAN) during infusion of CIM at 0, .05, .1, .3, .7, 1 and 3 micrograms/ min. Close arterial infusion of CIM in the hindlimb of steers can be used to achieve a local concentration elevation that is required to differentiate local and systemic effects in vivo. Calculated plasma threshold CIM concentration required to initiate cardiovascular responses was 21 pg/mL, which resulted from an infusion rate of .3 microgram/min. Threshold concentrations of CIM for stimulation of NEFA and lactate net flux in the hindlimb were 38 and 34 pg/mL, respectively, and would be achieved with an infusion rate of .7 microgram/min. All measured responses except AAN net flux exhibited significant linear and quadratic dose effects, and responses in the treated hindlimb were always severalfold greater than in the contralateral control hindlimb. Maximal differences between treated and control hindlimb blood flow occurred with a CIM infusion rate of .7 microgram/min, but the highest infusion rate (3 micrograms/min) was required to maximize differences in NEFA and lactate flux. Therefore, to minimize cardiovascular and other systemic responses and optimize direct hindlimb responses, an infusion rate of .5 microgram of CIM/ min should cause significant stimulation of beta-adrenergic receptors only in the CIM-infused hindlimb of young, growing steers.

Adrenergic beta-Agonists↗
PubMed2004

Compensatory load redistribution of horses with induced weightbearing hindlimb lameness trotting on a treadmill.

REASONS FOR PERFORMING STUDY: The compensatory mechanisms of horses with weightbearing hindlimb lameness are still not fully understood. HYPOTHESIS: That weightbearing, unilateral hindlimb lameness would not only alter stride characteristics to diminish structural stress in the affected limb but also induce compensatory load adjustments in the other supporting limbs. OBJECTIVE: To document the load and time shifting mechanisms of horses with unilateral weightbearing hindlimb lameness. METHODS: Reversible lameness was induced in 8 clinically sound horses by applying a solar pressure model. Three degrees of lameness (subtle, mild and moderate) were induced and compared with the nonlame (sound) control measurement. Vertical ground reaction forces were recorded for all 4 limbs simultaneously on an instrumented treadmill. RESULTS: Compared to the sound situation, moderate hindlimb hoof lameness induced a decrease in stride duration (-3.3%) and stride impulse (-3.1%). Diagonal impulse decreased selectively in the lame diagonal stance (-7.7%). Within the diagonal limb pair, vertical impulse was shifted to the forelimb during the lame diagonal stance (+6.5%) and to the hindlimb during the sound diagonal stance (+3.2%). Peak vertical force and vertical impulse decreased in the lame limb (-15%), but only vertical impulse increased in the contralateral hindlimb (+5.7%). Stance duration was prolonged in both hindlimbs (+2.5%). Suspension duration was reduced to a greater extent after push-off of the lame diagonal limb pair (-21%) than after the sound diagonal limb pair (-9.2%). CONCLUSIONS: Four compensatory mechanisms could be identified that served to reduce structural stress, i.e. peak vertical force on the affected limb: 1) reduction of the total vertical impulse per stride; 2) diagonal impulse decreased selectively in the lame diagonal; 3) impulse was shifted within the lame diagonal to the forelimb and in the sound diagonal to the hindlimb; and 4) the rate of loading and peak forces were reduced by prolonging the stance duration. POTENTIAL RELEVANCE: Load shifting mechanisms are not only effective in diminishing peak forces in the affected limb, but also suppress compensatory overload in other limbs. Selected force and time parameters allow the unequivocal identification of the lame limb. Future studies have to examine how far these compensatory mechanisms may be generalised for other defined orthopaedic problems in the hindlimb.

Adaptation, Physiological↗
PubMed1992

Hindlimb proportions, allometry, and biomechanics in Old World monkeys (primates, Cercopithecidae).

The traditional focus on morphological rather than mechanical units has obscured some significant functional differences in the hindlimbs of primates. This paper examines the allometric and biomechanical basis for some distinctive proportional differences among pairs of morphological units in the hindlimb, and especially the foot, of cercopithecid primates. Five major conclusions are reached. First, many hindlimb dimensions scale allometrically with body mass to maintain mechanical similarity within taxonomic and locomotor groups. Therefore, the majority of traditional indices which describe the shape of the foot within cercopithecids reveal differences which are primarily a function of size. Second, the hindlimb segments in colobines, and especially in Presbytis, are relatively long, probably to enhance leaping. Third, the major distinction of terrestrial cercopithecines among the features analysed is reduction in the length of the phalanges, due to the reduced importance of grasping during locomotion and the assumption of digitigrady. Fourth, Theropithecus and male Erythrocebus have high crural indices, relative to their body masses, which can facilitate curosoriality. Female E. patas already has a high crural index as a function of its body mass. Fifth, macaques form a distinctive group among cercopithecines, characterized by relatively short hindlimbs. Relatively very short hindlimbs in Macaca fuscata and M. thibetana suggest that climatic conditions can have an added effect on the lengths of the hindlimb segments. In summary, this analysis of the lengths of the hindlimb segments relative to body size reveals taxonomic differences which are due in part to phylogeny, to differences in locomotor behavior, and to substrate use.

Analysis of Variance↗
PubMed1984

Development of hindlimb locomotor behavior in the frog.

Hindlimb motor behavior of the larval frog (tadpole) begins during midlarval life and occurs with increasing frequency until the tail degenerates during metamorphosis. The threshold for hindlimb withdrawal in response to tactile stimulation is low during premetamorphic stages and rises dramatically during metamorphosis. Testing tadpoles in different environments altered the stage of development at which different hindlimb behaviors were first observed but did not change the ontogenetic sequence of behavioral development. However, even under conditions most favorable to hindlimb locomotion, behavioral expression lagged behind electrophysiological expression. The rates of tail beating, hindlimb stepping, and frog kicks are similar to the rate of bursting of tail and hindlimb motoneurons of the isolated nervous system, but their coordination is variable, whereas that recorded from the isolated CNS is fixed. Because neural mechanisms of hindlimb locomotion are functional prior to their behavioral use, the basic hindlimb locomotor circuits must develop without benefit of practice or sensory feedback. However, sensory activity modulates coordination and alters the probability that particular behaviors will be expressed. Implications of these results for studies of early behavior in other species, and the problem of inferring neural maturity from behavioral observations, are discussed.

Animals↗
PubMed1987

Different dopamine receptor subtypes mediate the neurogenic vasodilation produced by fenoldopam and SK & F 85174 in the dog hindlimb.

The present study was performed to examine the effects of the mixed DA-1/DA-2 receptor agonist. SK & F 85174, on hindlimb vascular resistance and identify the DA receptor subtypes involved in the neurogenic hindlimb vasodilation produced by this compound. Bilateral hindlimb perfusion at controlled flow rates was carried out in anesthetized dogs and one hindlimb was surgically denervated whereas the other limb was kept neurally intact. Intravenous administration of SK & F 85174 and fenoldopam, a DA-1 receptor agonist, produced decreases in mean blood pressure and in the perfusion pressure in the innervated limb. Perfusion pressure in the denervated limb was not altered by fenoldopam and was increased by SK & F 85174. The DA-2 receptor antagonist, S-sulpiride, inhibited the neurogenic vasodilation produced by SK & F 85174 but not that produced by fenoldopam. The DA-1 receptor antagonist, SCH 23390, did not alter the hindlimb vasodilatory effects of either SK & F 85174 or fenoldopam in these animals, but it antagonized the hypotensive responses to both of these agents. Intra-aortic administration of SK & F 85174 and fenoldopam also resulted in neurogenic hindlimb vasodilation with the maximum response to fenoldopam occurring significantly faster than SK & F 85174 (2.5 +/- 0.16 vs. 9.8 +/- 1.2 s). S-Sulpiride antagonized the hindlimb vasodilation produced by SK & F 85174 but not by fenoldopam. R-Sulpiride antagonized the hindlimb vasodilatory effect of fenoldopam.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed2001

Somatotopic arrangement and corticocortical inputs of the hindlimb region of the primary motor cortex in the macaque monkey.

Using Japanese monkeys, we examined the somatotopic organization of the hindlimb region of the primary motor cortex (MI) with intracortical microstimulation. In the hindlimb region of the MI, areas representing distal movements (digits and ankle joints) were basically surrounded by those representing proximal movements (knee and hip joints). Thus, the hindlimb region of the MI has a nested or horseshoe-like somatotopic representation. We then examined the topographic organization of corticocortical projections to the hindlimb region of the MI by the retrograde double-labeling technique: one monkey received paired injections of Fast blue (FB) and Diamidino yellow (DY) into hindlimb or forelimb representation of the MI, respectively, while two monkeys received those of FB and DY into proximal or distal representation of the hindlimb region of the MI, respectively. The neurons projecting to the hindlimb region of the MI were located in cortical areas largely separate from those projecting to the forelimb region of the MI. On the other hand, we found a substantial overlap of corticocortical neurons projecting to the proximal and distal parts of the hindlimb region of the MI in the dorsal division of the premotor cortex and the cingulate motor areas.

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