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At least 307 records · Page 17Linked to original sources
PubMed1993

Motor cortical activity during voluntary gait modifications in the cat. I. Cells related to the forelimbs.

1. The discharge patterns of 91 identified pyramidal tract neurons (PTNs), located within the forelimb region of area 4 of the cat motor cortex, were recorded during the voluntary modifications of gait needed to step over obstacles attached to a moving treadmill belt. Recordings were made simultaneously from flexor and extensor muscles acting around the shoulder, elbow, wrist, and digits of the forelimb contralateral to the recording site. 2. Analysis of the changes in electromyographic (EMG) activity during the gait modification showed increases in the activity of most flexor muscles of the shoulder and elbow, as well as in the wrist and digit dorsiflexors, when the contralateral forelimb was the first to pass over the obstacle. This period of augmented activity could be subdivided into two parts: one associated with the initial flexion of the limb that was needed to bring it above and over the obstacle (phase I), and the second associated with increased wrist dorsiflexor muscle activity before foot contact (phase II). 3. The discharge frequency of a total of 57/91 (63%) of the recorded PTNs was significantly increased during the gait modification when the limb contralateral to the recording site was the first to step over the obstacle; six of these neurons also showed a significant decrease in their discharge in a different part of the step cycle. In a further 21/91 (23%) neurons, discharge frequency was only decreased, whereas the remaining 13/91 (14%) PTNs showed similar patterns of activity both during control walking and during the gait modifications. 4. Most of those neurons (47/57) in which significant increases in firing frequency were observed, discharged maximally during the period of increased activity of the physiological flexor muscles. Twenty-three of these cells (23/47) discharged maximally in phase I, and 12 (12/47) in phase II. A third population of PTNS (12/47) started to increase their discharge in the stance phase of the step cycle immediately preceding the modified cycle. Seven (7/57) PTNs increased their discharge during the stance phase of the modified cycle, and the remaining three could not be classified as being preferentially related to any one part of the step cycle. 5. The frequency modulation of 41/57 PTNs was less when the leg contralateral to the recording site was the second to encounter the obstacle. In many neurons there was also an appreciable change in the time in the step cycle that peak discharge occurred. These changes in amplitude and timing paralleled the changes observed in the temporal relationships of the muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Character phylogeny of the primate forelimb superficial venous system.

The ontogeny and comparative anatomy of the forelimb superficial veins were investigated in humans, non-human primates and other mammals. Adult humans and the orangutan (Pongo) possess two autonomous forelimb veins, one on the lateral (preaxial) margin of the limb, the other on the medial (postaxial) margin. All other adult primates and mammals examined possess a lateral vein alone. In African apes (Pan and Gorilla) and in 24% of human forelimbs the lateral vein is short, being essentially confined to the antebrachial region, whereas in other mammals and in 76% of human limbs the lateral vein runs from the carpus to the clavicular region. In humans the medial vein develops before the lateral vein, whereas in the rabbit and the pig the medial vein is present in early embryos but is subsequently lost. We propose that in humans, and probably also in the orangutan, the possession of a medial vein is a neotenic retention of a primitive tetrapod condition. These animals, which retain their medial vein, are united by losing a late stage in their ontogeny. Other animals subsequently pass through a stage in which the medial vein is lost, but Pongo and Homo retain this vein to adulthood. The loss of an ontogenetic stage can arise independently, and the presence of a medial vein therefore affords only weak evidence for a close phylogenetic relationship between humans and the orangutan. The polymorphic lateral vein of humans may be a character state that is intermediate between the derived (short) lateral vein of the African apes and the primitive long lateral vein of other non-human primates and mammals.

Animals↗
PubMed1981

Interactions among inflammatory mediators on edema formation in the canine forelimb.

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.

Animals↗
PubMed2003

Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo.

Transcriptional cascades responsible for initiating the formation of vertebrate embryonic structures such as limbs are not well established. Limb formation occurs as a result of interplay between fibroblast growth factor (FGF) and Wnt signaling. What initiates these signaling cascades and thus limb bud outgrowth at defined locations along the anteroposterior axis of the embryo is not known. The T-box transcription factor TBX5 is important for normal heart and limb formation, but its role in early limb development is not well defined. We report that mouse embryos lacking Tbx5 do not form forelimb buds, although the patterning of the lateral plate mesoderm into the limb field is intact. Tbx5 is not essential for an early establishment of forelimb versus hindlimb identity. In the absence of Tbx5, the FGF and Wnt regulatory loops required for limb bud outgrowth are not established, including initiation of Fgf10 expression. Tbx5 directly activates the Fgf10 gene via a conserved binding site, providing a simple and direct mechanism for limb bud initiation. Lef1/Tcf1-dependent Wnt signaling is not essential for initiation of Tbx5 or Fgf10 transcription, but is required in concert with Tbx5 for maintenance of normal levels of Fgf10 expression. We conclude that Tbx5 is not essential for the early establishment of the limb field in the lateral plate mesoderm but is a primary and direct initiator of forelimb bud formation. These data suggest common pathways for the differentiation and growth of embryonic structures downstream of T-box genes.

Animals↗
PubMed1997

Hoxb-8 has a role in establishing early anterior-posterior polarity in chick forelimb but not hindlimb.

The distribution of Hoxb-8 transcripts through the chick flank and early forelimb mirrors the distribution of polarizing activity in the flank at these early stages. Polarizing activity displayed by Hoxb-8-expressing tissue is only realised when placed adjacent to the AER and appears to be mediated through Shh induction, suggesting that Hoxb-8 may lie genetically upstream of Shh. Accordingly, Hoxb-8 expression is rapidly induced by retinoic acid (RA) treatment in the anterior of the forelimb in a spatial and temporal manner that is consistent with the induction of Shh and formation of the ZPA. Furthermore, inhibition of RA synthesis in the flank downregulates the expression of endogenous Hoxb-8 and results in the loss of Shh expression. However, once the ZPA has become established the posterior limb mesoderm displays resistance to the induction of Hoxb-8 expression. Grafting of ZPA cells to the anterior of a host limb renders the host anterior tissue resistant to RA-induced Hoxb-8 expression. These results indicate that Hoxb-8 expression may be regulated by the established ZPA through a negative feedback loop. The anterior AER also secretes an inhibitory factor, preventing RA-induced or already established Hoxb-8 expression in the cells immediately underneath the AER. Consistent with a role for Hoxb-8 in positioning of the forelimb ZPA, Hoxb-8 expression is not seen in RA-induced duplications at the anterior of the hindlimb. However, grafting of Hoxb-8-expressing tissue to the hindlimb can lead to Shh expression and similar duplications, suggesting that factors mediating ZPA formation are very similar in both wing and leg.

Animals↗
PubMed2006

Subthalamic stimulation-induced forelimb dyskinesias are linked to an increase in glutamate levels in the substantia nigra pars reticulata.

The neurobiological mechanisms by which high-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates the motor symptoms of Parkinson's disease (PD) remain unclear. In this study, we analyzed the effects of STN-HFS on motor behavior in intact or hemiparkinsonian rats (6-hydroxydopamine lesion of the substantia nigra pars compacta) and investigated the correlation between these effects and extracellular glutamate (Glu) and GABA levels, assessed by intracerebral microdialysis in the substantia nigra pars reticulata (SNr). STN-HFS at an intensity corresponding to the threshold inducing contralateral forelimb dyskinesia, increased Glu levels in the SNr of both intact and hemiparkinsonian rats. In contrast, STN-HFS at half this intensity did not affect Glu levels in the SNr in intact or hemiparkinsonian rats but increased GABA levels in hemiparkinsonian rats only. STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr. These new neurochemical data suggest that STN-HFS-induced forelimb dyskinesia is mediated by glutamate, probably via the direct activation of STN axons, shedding light on the mechanisms of STN-HFS in PD.

Animals↗
PubMed1992

Muscle activity during forelimb stepping in decerebrate cats.

In decerebrate cats with the lower thoracic cord transected, electromyographic activities were analyzed in up to 41 forelimb muscles, almost all muscles involved in forelimb stepping (intrinsic hand muscles were not included). From the active period in the step cycle, muscles were classified into three groups: extensors, of which activity is like that of elbow extensors; flexors, activity like that of elbow flexors; others, including dorsiflexors of the wrist, pronators, and supinator. The results were well consistent with those from conscious animals as well as efferent pattern of fictive locomotion in elbow and distal muscles. Nevertheless, in some proximal muscles discrepancies were noted, suggesting their changeability depending on environmental conditions. Recording from almost all muscles allowed to estimate rhythmic change of the overall output of the forelimb central pattern generator.

Animals↗
PubMed2004

Determination of passive mechanical properties of the superficial and deep digital flexor muscle-ligament-tendon complexes in the forelimbs of horses.

OBJECTIVE: To determine the relative contributions of the muscles, tendons, and accessory ligaments to the passive force-length properties of the superficial (SDF) and deep digital flexor (DDF) myotendinous complexes. SAMPLE POPULATION: 8 cadaveric forelimbs from 6 adult Thoroughbreds. PROCEDURE: In vitro, limb configurations during slack position and myotendinous lengths during subsequent axial loading of forelimbs were recorded before and after transection of accessory ligaments. Expressions were derived to describe the force-length behavior of each muscle, tendon, and accessory ligament-tendon unit; linear stiffness was computed for these components. The elastic modulus was established for the SDF and DDF tendons. RESULTS; Linear stiffness was 2.80 +/- 0.38 kN/cm for the SDF muscle, 3.47 +/- 0.66 kN/cm for the DDF muscle, 2.73 +/- 0.18 kN/cm for the SDF tendon, 3.22 +/- 0.20 kN/cm for the DDF tendon, 6.46 +/- 0.85 kN/cm for the SDF accessory ligament, 1.93 +/- 0.11 kN/cm for the SDF accessory ligament-tendon unit, and 2.47 +/- 0.11 kN/cm for the DDF accessory ligament-tendon unit. The elastic modulus for the SDF and DDF tendons was 920 +/- 77 and 843 +/- 56 MPa, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Both the muscle-tendon and ligament-tendon portions of SDF and DDF myotendinous complexes had important roles in supporting the forelimb of horses. Although muscle tension can be enhanced by elbow joint flexion and active contraction, the accessory ligaments transmitted more force to the distal tendons than did the muscles under the conditions tested.

Animals↗
PubMed2005

Association between subjective lameness grade and kinetic gait parameters in horses with experimentally induced forelimb lameness.

OBJECTIVE: To evaluate the association between subjective lameness grades and kinetic gait parameters and assess the variability in kinetic parameters in horses with experimentally induced forelimb lameness. ANIMALS: 32 horses. PROCEDURES: Forelimb lameness was induced in each horse via injection of lipopolysaccharide into 1 metacarpophalangeal joint (40 experimental trials). Subjective lameness grading and 13 kinetic gait parameters (force plate analysis) were assessed before (baseline) and at 12, 18, and 24 hours after lipopolysaccharide injection. While horses were trotting, kinetic gait analysis was performed for 8 valid repetitions at each time point. Repeated-measures analyses were performed with 8 repetitions for each kinetic parameter as the outcome, and lameness grades, time points after lipopolysaccharide injection, and repetition order as explanatory variables. Sensitivity and specificity of kinetic parameters for classification of horses as sound or lame (in relation to subjective lameness scores) were calculated. Between- and within-horse variabilities of the 13 kinetic parameters were assessed by calculation of coefficients of variation. RESULTS: Subjective lameness grades were significantly associated with most of the kinetic parameters. Vertical force peak and impulse had the lowest between- and within-horse coefficients of variation and the highest correlations with subjective lameness grade. Vertical force peak had the highest sensitivity and specificity for lameness classification. Vertical force peak and impulse were significantly decreased even in horses with mild or unobservable lameness. CONCLUSIONS AND CLINICAL RELEVANCE: Among the kinetic gait parameters, vertical force peak and impulse had the best potential to reflect lameness severity and identify subclinical forelimb gait abnormalities.

Animals↗
PubMed2006

Evaluation of signs of postoperative pain and complications after forelimb onychectomy in cats receiving buprenorphine alone or with bupivacaine administered as a four-point regional nerve block.

OBJECTIVE: To evaluate signs of postoperative pain and complications after forelimb onychectomy in cats receiving buprenorphine alone or with bupivacaine administered as a 4-point regional nerve block. DESIGN: Prospective, randomized, double-blind clinical trial. ANIMALS: 20 cats. PROCEDURE: All cats received buprenorphine (0.01 mg/kg [0.004 mg/lb], IM) preoperatively. One forelimb of each cat also received bupivacaine (1 mg/kg [0.45 mg/lb] of a 0.75% solution) administered as a 4-point regional nerve block. After onychectomy, discomfort (lameness, foot reaction, and pain) scores were evaluated by 2 experienced observers 2, 4, 6, 8, 24, and 168 hours postoperatively. Complication (hemorrhage, swelling, and infection) scores were evaluated 24 and 168 hours postoperatively. Surgeries were performed by 1 experienced veterinary surgeon. Rescue analgesia was provided if needed. RESULTS: 6 cats required rescue analgesia postoperatively. There was no difference in discomfort or complication scores between control limbs and limbs in which a nerve block was administered. Additionally, there was no difference in discomfort and complication scores between cats that did or did not require rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Bupivacaine administered as a 4-point regional nerve block in addition to a systemic analgesic did not decrease discomfort or complication scores in cats undergoing forelimb onychectomy.

Analgesia↗
PubMed2006

Forelimb amputation for treatment of a peripheral nerve sheath tumor in an African pygmy hedgehog.

CASE DESCRIPTION: A 6-year-old female African pygmy hedgehog was evaluated because of a mass of unknown duration on the lateral aspect of the right shoulder region. CLINICAL FINDINGS: A fine-needle aspirate of the mass was collected for cytologic examination; findings were consistent with a spindle cell tumor. A CBC, plasma biochemical analyses, and whole-body radiography revealed no other abnormalities. TREATMENT AND OUTCOME: An initial surgery performed in an attempt to remove the mass with preservation of the limb failed in that tumor-free surgical margins were not obtained. Histologically, the mass was identified as a peripheral nerve sheath tumor (neurofibrosarcoma). A second surgery to amputate the forelimb was successful. After 1 year, there had been no further development of peripheral nerve sheath tumor at this or other sites. CLINICAL RELEVANCE: In African pygmy hedgehogs, potential differential diagnoses for a subcutaneous mass should include peripheral nerve sheath tumor. If necessary, forelimb amputation can be performed successfully in this species with procedures modified from those used in dogs. Information gathered during the treatment and recovery of the hedgehog of this report may assist practicing veterinarians in counseling owners of hedgehogs that are undergoing forelimb amputation with regard to the course of recovery that may be expected following this procedure.

Amputation, Surgical↗
PubMed2000

The forelimb in walking horses: 2. Net joint moments and joint powers.

The objective was to measure the net joint moments and joint powers for the joints of the equine forelimb during the walk. Videographic and force data were combined with morphometric information using an inverse dynamics method. During stance phase the predominant joint moment was on the palmar aspect of all forelimb joints except the shoulder, where the peak moment was considerably higher than at any other joint. The entire forelimb showed net energy absorption in both stance and swing phases. The elbow was the only joint that showed net generation of energy, which was used to maintain the limb in extension in early stance as the horse's body vaults over the limb and to drive protraction and retraction of the limb during swing. The carpus aligned the limb into a supportive strut, but did not play an important role in energy absorption or generation. A small burst of positive work on the flexor aspect at the start of breakover indicated that the carpus played an active role in initiating breakover during walking. The fetlock functioned elastically to store and release strain energy during stance. The coffin joint acted as an energy damper during most of stance with a small burst of energy generation on the flexor aspect as the joint flexed during breakover. The magnitude of the peak joint power during swing decreased in a proximal to distal sequence. It is concluded that the elbow joint is the main site of energy generation. The shoulder and coffin joints act as energy dampers during stance. The distal joints had very low joint powers and appeared to be driven by inertial forces during the swing phase. This information will be applied to describe how horses compensate for different lamenesses in terms of redistributing the functions of energy generation and absorption between joints.

Animals↗
PubMed2000

The forelimb in walking horses: 1. Kinematics and ground reaction forces.

Video (60 Hz) and force (2000 Hz) data were collected from 5 sound horses during walking. Forelimb data were analysed for 8 strides (4 left, 4 right) per horse to determine sagittal plane kinematics and ground reaction forces (GRFs). The results suggested that brachial rotation was responsible for protraction and retraction of the limb as a whole, while rotations of the scapula and antebrachium elevated the distal limb during breakover and early swing then lowered it in preparation for ground contact. The coffin joint was flexed maximally at the time of peak longitudinal braking force, which occurred during breakover of the contralateral forelimb. The metacarpus was vertical at 28% stride. This was considerably earlier than the change from a braking to a propulsive longitudinal force (34% stride), which coincided with maximal extension of the fetlock joint. The longitudinal propulsive force peaked just after contact of the contralateral forelimb. During the swing phase the joints distal to the shoulder showed a single flexion cycle that peaked at 76% stride at the carpus, 81% stride at the fetlock and 84% stride at the elbow and coffin joints. The coffin and shoulder joints began to extend in the terminal swing phase and continued to extend through ground contact and early stance. The results provide normative data that will be applied in detecting changes in kinematics and ground reaction forces that are associated with specific lamenesses.

Animals↗
PubMed2005

Three-dimensional kinematics of the equine distal forelimb: effects of a sharp turn at the walk.

REASONS FOR PERFORMING STUDY: Sharp turns are suspected to increase expression of several distal forelimb lamenesses even at the walk but the biomechanical consequences of such a movement remain unknown. OBJECTIVE: To quantify the effects of a sharp turn at the walk on the 3-dimensional movements of the distal segments of the forelimb. METHODS: Kinematics of the distal segments were measured in 4 healthy horses invasively with an ultrasonic system. Three-dimensional rotations of the digital joints were calculated by use of a joint coordinate system. Data obtained for a turn at the walk were compared to those obtained in a straight line. RESULTS: During the stance phase in a turn, the inside forelimb underwent an adduction that induced lateromotion and medial rotation in the distal interphalangeal joint and medial rotation in the proximal interphalangeal joint. These movements were maximal at heel-off and decreased during breakover as the hoof underwent a sudden lateral rotation. CONCLUSIONS: Walking in a sharp turn affects the kinematics of the digital joints outside the sagittal plane. POTENTIAL RELEVANCE: This knowledge offers the opportunity to derive hypotheses on biomechanical factors that could contribute to the pathogenesis of digital injuries and on consequences for rational shoeing.

Animals↗
PubMed1976

The response of the brachial ventral horn or Xenopus laevis to forelimb amputation during development.

The normal development of the brachial ventral horn of the frog Xenopus laevis and the response of the brachial ventral horn to complete forelimb extirpation at five developmental stages were assessed histologically. Differentiation of brachial ventral horn neurons occurred in pre-metamorphic tadpoles between stages 52/53 and 57. Mean cell number in the brachial ventral horn reached a peak of 2576 (S.E.M. equals +/- 269, N equals 2) per side of the spinal cord at stage 55 and decreased to 1070 (S.E.M. equals +/- 35, n equals 7) by the end of metamorphosis. Cell degeneration was presumed to be the mode of cell loss since it was most prevalent during the period of rapid decrease in cell numbers. The response of the ventral horn to forelimb removal varied with the stage of the animal at amputation. Following amputation at stage 52/53 or 54 the ipsilateral ventral horn neurons appeared less differentiated than those on the control side and a rapid cell loss of about 80% occurred on the operated side. These effects occurred more rapidly after ablation at stage 54 than at stage 52/53. Amputation at stage 58, 61, or 66 caused chromatolysis in the ventral horn, a period of relative cell excess on the operated side, and a delayed neuronal loss of 32-66%. It was concluded that excess cell degeneration accounted for cell loss and that suppression of normal neuronal degeneration caused the relative cell excess on the operated side. The data indicate that the brachial ventral horn was indifferent to the periphery before stage 54, was quickly affected by limb removal between stages 54 and 58, and by stage 58 had entered a phase in which a delay preceded cell death. No forelimb regeneration occurred.

Age Factors↗
PubMed1976

Callosal transfer of impulses originating from superficial and deep nerves of the cat forelimb.

1. Experiments were performed in 18 chloralose-anaesthetized, curarized cats in order to study the callosal transfer of somatic information originated in exteroceptive and proprioceptive receptors. Several cutaneous and deep nerves of the forelimb were prepared and stimulated with graded intensities, so as to activate selectively afferent fibres pertaining to the different groups of Lloyd's classification. Simultaneous records were taken (and averaged on-line by means of a multichannel analyzer) from the distal end of a cut dorsal rootlet (C7-C8), from the cerebral cortex (SI, SII or area 3a, according to the experiment) and from the somesthetic callosal region (SCR). 2. The low-threshold afferent fibres (Group II) of cutaneous origin were found to have a wide projection to the SCR, with the maximal density in its middle portion. Some of the fastest corticocallosal impulses are relayed monosynaptically at cortical level. Plots of the amplitude of cortical and callosal responses as a function of stimulus strength showed that both central responses have the same threshold and exhibit a parallel, sharply-rising amplitude increase, thus suggesting that the cortico-callosal re-transmission system for afferent impulses of cutaneous origin is very powerful in nature. Impulses elicited in afferent fibres of higher threshold (Group III) do not enhance the cortical and callosal positive waves provoked by Group II afferent volleys. 3. Afferent fibres of deep origin were also found to send a wide projection to the SCR, although less substantial than that of cutaneous fibres. Stimulation of the deep radial nerve elicited mass responses in the whole SCR, provided the strength of stimuli was high enough to engage the Group II fibres. Only in the central portion of the SCR were small potentials recorded in response to pure Group I volleys of DRN. Experiments performed with selective stimulation of pure muscular branches of forelimb deep nerves as well as of articular and mixed (muscular and articular) branches gave evidence making it possible to ascertain the origin of deep afferent fibres projecting to the SCR. Stimulation of the forelimb muscular branches with strength provoking full activation of Group I afferent and additional engagement of those of Group II, did not provoke mass responses in the whole extent of the SCR. In order to obtain callosal potentials upon stimulation of pure muscular nerves, it was necessary to increase the stimulus strength at or above the threshold for Group III fibres. On the contrary, the same callosal foci unresponsive to Group I and II muscular afferent volleys exhibited clear-cut responses to stimulation of the lowest-threshold Group I and/or Group II afferents of articular and mixed nerves. From the results it might be inferred that only proprioceptive information originating from articular receptors and from extrafusal muscular afferents has access to the callosal interhemispheric transfer.

Animals↗
PubMed1999

Pharmacokinetics of intra-arterial delivery of tacrolimus to vascularly isolated rabbit forelimb.

A vascularly isolated rabbit forelimb model simulating conditions of composite tissue allografting was used to determine the regional pharmacokinetic advantage achievable in extremity tissue components during i.a. tacrolimus (FK506) administration. FK506 was infused continuously via osmotic minipump into the right brachial artery of New Zealand rabbits at 0.05, 0.1, and 0.2 mg/kg/day. On day 6, FK506 concentrations were measured in aortic whole blood, heart, lung, liver, kidney, spleen, and fat, as well as in skin, muscle, bone, and bone marrow samples from both right and left forelimbs. The relative tissue concentrations of FK506 in descending order were [spleen approximately lung approximately kidney] > [heart approximately skin approximately muscle] > [fat approximately bone marrow] > [liver approximately bone approximately blood]. In marked contrast to previous results with i.a. cyclosporin A infusion, only a minimal regional advantage of local FK506 delivery (mean right/left concentration ratios 1.0-1.4) was obtained in all forearm tissues over the dose range studied. For each limb tissue, left-sided FK506 concentrations significantly correlated with systemic blood levels, and the left-sided tissue-to-whole-blood concentration ratio did not vary significantly with dose. We conclude that FK506 is pharmacokinetically inferior to cyclosporin A for continuous i.a. administration to the vascularly isolated rabbit forelimb, and hypothesize that this difference is the result of differences in the distribution of each drug within whole blood. Our findings suggest that, despite its demonstrated efficacy in experimental and clinical transplantation, FK506 would not be an appropriate immunosuppressant to deliver via the i.a. route for prevention of limb allograft rejection.

Animals↗
PubMed1992

Relationship between innervation and forelimb regenerative capacity in the postmetamorphic pond frog Rana brevipoda porosa.

The limb regenerative capacity and the quantity of innervation (the percentage of a cross-sectional area of amputation forelimb stump occupied by nerves) in the pond frog, Rana brevipoda porosa, was investigated in postmetamorphic froglets and adults of various sizes by means of amputating forelimbs through the zeugopodium. Nearly all the amputated limbs of newly metamorphosed froglets, 18-19 mm in snout-vent length, showed heteromorphic regeneration. However, the larger the body size, the lower the presence of limb regeneration. Limb regenerative capacity was completely lost in froglets and adults with snout-vents larger than 35 mm. The quantity of innervation of limbs was highest in newly metamorphosed froglets, gradually decreasing with growth. The nerve quantity in adults with a snout-vent length between 60-67 mm was approximately half that of the froglets. When the nerve supply was augmented by deviating ipsilateral sciatic nerve bundles to the forelimb stump, almost all limbs, which were usually non-regenerative with normal innervation, regenerated heteromorphically. These results show that the decline in limb regenerative capacity during postmetamorphic growth is in part attributable to the reduction in innervation levels to below the threshold level required for regeneration.

Animals↗