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Influence of fasting on leucine and muscle protein metabolism across the human forearm determined using L-[1-13C,15N]leucine as the tracer.

1. We have used L-[1-13C,15N]leucine as the substrate tracer to study leucine and muscle protein metabolism across the forearm of eight normal fasting adults. 2. The rates of protein synthesis and breakdown, de- and re-amination of leucine, and the oxidative decarboxylation of its keto acid were calculated directly from the arteriovenous metabolite balances and isotope dilutions as described by the metabolic model. 3. The results were compared with those obtained previously when subjects were fed. The effects of fasting on protein and leucine metabolism were a significant decrease in protein synthesis from 127 (SEM 11; n = 6) to 70 (SEM 6; n = 12) nmol of leucine min-1 100 ml-1 of forearm tissue (P less than 0.001) and a marked decrease in leucine catabolism in the forearm muscle. 4. This model has demonstrated that each subject was in negative protein balance across the forearm during fasting while positive during feeding, the mean values being -29(SEM 5; n = 12) and +39(SEM 9; n = 6) nmol of leucine min-1 100 ml-1 of forearm tissue respectively. 5. These results are sufficiently encouraging to suggest a role for this model in future studies on muscle protein metabolism.

Adult↗

Role of nitric oxide towards vasodilator effects of substance P and ATP in human forearm vessels.

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-L-arginine (4 or 8 mumol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of L-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-L-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of L-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Acetylcholine↗

Effects of tumour necrosis factor-alpha in the human forearm: blood flow and endothelin-1 release.

Increased circulating concentrations of tumour necrosis factor-alpha (TNF-alpha) are seen in several pathological conditions associated with vascular disease. TNF-alpha induces the synthesis of endothelin-1 (ET-1), a potent vasoconstictor, by the endothelium. However, there is profound vasodilatation in sepsis, where circulating levels of both ET-1 and TNF-alpha are elevated. The details of the interaction between ET-1 and TNF-alpha and the predominant resulting haemodynamic effect in healthy humans are unclear. The aim of the present study was to determine the effects of intra-arterial TNF-alpha on ET-1 spillover, vascular tone and endothelial function in the healthy human forearm. Brachial arterial and deep venous blood samples, forearm plasma flow measurements and blood flow responses to acetylcholine and sodium nitroprusside were obtained in six healthy subjects before and during a 6 h infusion of TNF-alpha into the brachial artery. Forearm blood flow was significantly greater than baseline during exposure to TNF-alpha [median (lower quartile, upper quartile): baseline, 2.6 (2.1, 2.8) ml.min(-1).100 ml(-1); TNF-alpha, 4.6 (4.5, 5.1) ml.min(-1).100 ml(-1); P <0.05]. The rate of release of ET-1 was significantly greater than baseline after 30 and 260 min of TNF-alpha infusion [median (lower quartile, upper quartile): baseline, 0.8 (0.6, 1.1) pg.min(-1).100 ml(-1); 30 min, 2.4 (1.9, 3.2) pg.min(-1).100 ml(-1); 260 min, 4.1 (3.1, 4.2) pg.min(-1).100 ml(-1); P <0.05]. The vasodilatory response to acetylcholine was diminished during TNF-alpha infusion, whereas the response to sodium nitroprusside remained unchanged. We thus demonstrate for the first time that local TNF-alpha increases ET-1 spillover from the human forearm and impairs endothelium-dependent vasodilatation. In spite of this action, TNF-alpha has a vasodilatory effect, resulting in an increase in forearm blood flow.

Acetylcholine↗

Thermogenic response to adrenaline during restricted blood flow in the forearm.

To elucidate the underlying mechanism behind the thermogenic effect of adrenaline in human skeletal muscle, nine healthy subjects were studied during intravenous infusion of adrenaline. Restriction of blood flow to one forearm was obtained by external compression of the brachial artery, to separate a direct metabolic effect of adrenaline from an effect dependent on increased blood flow. The other arm served as the control arm. In the control arm, the forearm blood flow increased 4.7-fold (from 2.0 +/- 0.3 to 9.3 +/- 1.5 mL 100 g(-1) min(-1), P < 0.001) during the adrenaline infusion. Adrenaline significantly increased forearm oxygen consumption (from 4.7 +/- 2.1 to 7.0 +/- 3.6 micromol 100 g(-1) min(-1), P < 0.025). In the arm with restricted blood flow, the forearm blood flow increased 2.9-fold (from 1.6 +/- 0.3 to 4.6 +/- 0.8 mL 100 g(-1) min(-1), P < 0.002) but the forearm oxygen consumption did not increase (baseline period: 5.6 +/- 2.3 micromol 100 g(-1) min(-1), adrenaline period: 6.1 +/- 2.1 micromol 100 g(-1) min(-1), P = 0.54). The experimental design and the difficulties in interpretation of the result are discussed. The results give evidence for the hypothesis that the vascular system plays a key role in the thermogenic effect of adrenaline in skeletal muscle in vivo.

Adipose Tissue↗

Intra-arterial substance P mediated vasodilatation in the human forearm: pharmacology, reproducibility and tolerability.

AIMS: The current studies were designed to characterize the pharmacology, reproducibility and tolerability of the vasodilator response to intra-arterial substance P infusion in the forearm of healthy man. METHODS: On different occasions, eight healthy male volunteers received brachial artery infusions of substance P at doubling doses ranging from 0.5 to 128 pmol min(-1). Blood flow was measured in both arms using venous occlusion plethysmography. RESULTS: Substance P induced dose-dependent vasodilatation in the human forearm which had a log-linear relationship to dose. At doses of 1-8 pmol min(-1), mean responses were highly reproducible both within and between days. There were no differences between responses to discontinuous doses and continuous doses of substance P. Substance P was generally well tolerated at doses of < or = 64 pmol min(-1) with no significant alteration in arterial blood pressure or heart rate. Skin oedema in the infused forearm and systemic vasodilatation, manifested by facial flushing and non-infused forearm vasodilatation, occurred at doses of > or = 16 pmol min(-1). CONCLUSIONS: Forearm vasodilatation to substance P represents a reproducible and useful model in the assessment of peripheral endothelial cell NK1 receptor function.

Adult↗

Arginine, lysine and ornithine as vasodilators in the forearm of man.

Nitric oxide is an endogenous vasodilator produced from L-arginine and oxygen by stereospecific enzymes. L-arginine itself can act as a vasodilator when administered at high doses to humans. This effect has been attributed by some to provision of extra substrate for production of nitric oxide. This work compares L-arginine-induced vasodilation with that caused by D-arginine, hyperosmolar sodium chloride and by other cationic amino acids in the resting forearm vasculature of normal subjects. By these means we identify whether L-arginine-induced vasodilation has a component related to stereospecific provision of substrate for nitric oxide production, or whether it can be accounted for by other phenomena. Effects of hyperosmolar sodium chloride and both L and D isomers of arginine, lysine and ornithine on forearm blood flow in eight normal male subjects were compared by bilateral forearm venous occlusion plethysmography. Vasodilator responses to saline and each amino acid were compared as the area under dose-response curves with single-factor analysis of variance (ANOVA). The magnitude of vasodilation obtained with the D isomers of each amino acid was compared with the L counterpart by application of single-factor ANOVA to the appropriate areas under dose-response curves. All three cationic amino acids increased forearm blood flow. Part of the increase could be related to the high osmolality of infusates-comparison with equiosmolar sodium chloride solutions shows that ornithine does not differ significantly as a vasodilator (P > 0.4), but that arginine and lysine have greater vasodilator effects than can be accounted for by osmolality alone (P < 0.001). The D isomers of arginine and lysine were more potent dilators than their L counterparts (arginine P < 0.03, lysine P < 0.02). The vasodilator effects of arginine in the forearm vascular bed at rest are not stereospecific, they are common to other cationic amino acids, greater for D isomers and occur only when normal plasma concentrations are raised far above the physiological range. These features suggest that the vasodilator effect of arginine is in part physical and related to the presence of the molecule in the vessel lumen. They do not suggest that increased provision of substrate, with a consequence of increased nitric oxide production, is the principal basis of L-arginine-induced vasodilation in normal humans.

Adolescent↗

Long-term oestrogen therapy is associated with improved endothelium-dependent vasodilation in the forearm resistance circulation of biological males.

1. The aim of the present study was to determine the effects of long-term oestrogen on resistance vessel reactivity in biological males. 2. Recent studies have demonstrated that long-term oestrogen therapy favourably alters the lipid profile and improves vasodilator function in the conduit arteries of biological males. Whether a similar benefit is exerted on the resistance circulation is not known. Therefore, we examined the effects of long-term oestrogen therapy on skeletal muscle resistance vessel function in biological males and the potential mechanisms by which it may exert its effects. 3. Forearm blood flow (FBF) and resistance were compared in 15 male-to-female transsexuals being prescribed oestrogen, with 14 age-matched healthy males, at rest and in response to the endothelium-dependent nitric oxide (NO) vasodilator acetylcholine (ACh), the endothelium-independent but NO-mediated vasodilator sodium nitroprusside (SNP), the endothelium-independent and non-NO-mediated vasodilator verapamil (VER) and the endothelium-independent vasoconstrictor phenylephrine (PE). 4. Basal blood flows were similar in the two groups. However, the male-to-female transsexuals had a significant upward and leftward shift in FBF responses to ACh compared with males, with a 52% increase in FBF responses at the highest dose of ACh used. Forearm blood flow in transsexuals rose from a mean (+/- SEM) baseline level of 3.02 +/- 0.25 to a maximum of 19.5 +/- 2.59 mL/min per 100 mL forearm tissue (compared with 3.24 +/- 0.41 and 9.43 +/- 1.97 mL/min per 100 mL forearm tissue, respectively, in males) with the highest dose of ACh (+2.73 micrograms/min per 100 mL; P < 0.0005). Forearm vascular resistance was also significantly reduced in transsexuals compared with males (P < 0.05). Vasodilator responses to SNP, VER and PE were similar in both groups. 5. There were no differences observed in total cholesterol and low-density lipoprotein-cholesterol levels. However, male-to-female transsexuals had 20% higher high-density lipoprotein-cholesterol levels compared with males (1.57 +/- 0.11 vs 1.26 +/- 0.08 mmol/L, respectively; P < 0.05) and 47% higher triglyceride levels (P < 0.005). Serum testosterone levels (an index of oestrogen therapy) was a predictor of responses to endothelium-dependent vasodilation (rs = -0.50; P < 0.01). 6. Long-term oestrogen therapy enhances endothelium-dependent vasodilation in the skeletal muscle microcirculation of biological males. The effects appear to be selective because endothelium-independent vasodilation and vasoconstriction are not altered.

Acetylcholine↗

Effects of a Ginkgo biloba extract on forearm haemodynamics in healthy volunteers.

The aim was to validate possible vasodilating effects of a Ginkgo biloba extract with a secondary aim of finding a pharmacodynamic signal relating to the active component of these extracts. We studied the effect of G. biloba extract on forearm haemodynamics in 16 healthy subjects (nine females, seven males) with a median age of 32 years (range: 21-47). The study was conducted as a randomized, double-blinded cross-over design using oral treatment with G. biloba extract (Gibidyl Forte(R) t.i.d. or placebo for 6 weeks. Forearm blood flow and venous capacity were measured by strain-gauge plethysmography. Blood pressure was measured by standard sphygmomanometry, and forearm vascular resistance (FVR) was derived. Measurements were made at baseline and after 3, 6, 9 and 12 weeks of treatment. Forearm blood flow was significantly higher during active treatment after 3 and 6 weeks as compared with placebo treatment for 3 and 6 weeks (P<0.05). Mean arterial blood pressure was unchanged, making the calculated FVR significantly lower during active treatment (P<0.02). It is concluded that oral treatment with a G. biloba extract (Gibidyl Forte(R)) is able to dilate forearm blood vessels causing increments in regional blood flow without changing blood pressure levels in healthy subjects. The increments in blood flow may be used as a biological signal for pharmacokinetic studies.

Adult↗

Role of the forearm interosseous ligament: is it more than just longitudinal load transfer?

The objective of our study was to measure 3-dimensional force vectors (magnitude and direction) acting in the forearm when load is applied to the hand and to measure the actual force in the interosseous ligament (IOL). Fourteen cadaveric forearms were loaded to 136 N of compression while special load cells measured force vectors in the forearm. Computer forearm models were used to display the 3-dimensional force vector directions. The study results showed that the radius bears most of the load at the wrist but load on the radius at the elbow is reduced because the IOL transfers load to the ulna between the wrist and the elbow. In addition to this role in longitudinal load transfer, our measurement of 3-dimensional forces allowed identification of transverse vectors which suggest that the IOL also functions to keep the radius and ulna from splaying apart. Our results imply that the IOL participates not only in longitudinal load transfer but also in the maintenance of transverse stability of the forearm during compressive load transfer from the hand to the elbow.

Aged↗

Selection of fusion position during forearm arthrodesis.

The purpose of this study was to determine the optimal position for forearm arthrodesis. We attempted to determine functional difficulties associated with different positions of simulated fusion and whether there was a difference between men and women in their preference for fusion position. The forearms of 30 subjects were immobilized in neutral, 45 degrees supination, and 45 degrees pronation. The subjects performed 2 functional tests in each splint: the Jebsen hand function test and a subjective evaluation of the difficulty of activities of daily living. Each subject was asked to choose a preferred position for forearm fusion. Overall, subjects found the supinated position the most difficult to adapt to; the majority (63.3%) preferred neutral. Based on the results of our study we recommend forearm fusion in neutral or slight pronation. A thorough preoperative activity history and functional assessment may assist in determining the desired forearm arthrodesis position in a given individual.

Activities of Daily Living↗

Biochemical composition and histologic structure of the forearm interosseous membrane.

PURPOSE: The purpose of this study was to determine the structure and composition of the forearm interosseous membrane (IOM). METHODS: The IOM of 12 cadaver forearms was fixed in formalin. After fixation 5 individual IOM fiber bundles per arm were separated by dissection, excised, and processed with hematoxylin-eosin, trichrome, and Verhoff-vanGeison stains. Nine additional fresh forearms were dissected and 5 IOM fiber bundles per arm were analyzed using the hydroxyproline assay. Bundles were evaluated at ulnar, central, and radial locations. RESULTS: Histologic analysis of the IOM bundles obtained from the 12 fixed forearms showed an abundance of collagen in the main bundle central location (84% +/- 7.8%). A progressive increase in collagen was noted from distal to proximal bundles (r =.72). The hydroxyproline assay of collagen content of the main IOM bundle's central location from the 9 additional fresh forearms was 99.3% +/- 16.5%. There was no difference between bundles or location (power = 0.25 and 0.46). CONCLUSIONS: We found that the IOM possesses a large collagen content arranged in fibrillar structures surrounded by elastin. Collagen was abundant in the proximal bundles and decreased in the distal bundles.

Aged↗

Forearm rescue cuff improves tourniquet tolerance during intravenous regional anesthesia.

BACKGROUND AND OBJECTIVES: Tourniquet pain during intravenous regional anesthesia (IVRA) of the upper limb is common and can limit tourniquet inflation time. We hypothesize that a forearm rescue cuff is better tolerated than the traditional rescue cuff of a double-cuff tourniquet. METHODS: After Institutional Review Board (IRB) approval and informed consent, 10 healthy unmedicated volunteers took part in a prospective, randomized, cross-over study. Following inflation of the proximal tourniquet cuff on the upper arm, a standardized IVRA with 0.5% lidocaine, 0.6 mL/kg was administered. When the volunteer complained of tourniquet pain, or at 30 minutes, the initial cuff was changed to a rescue cuff. During session A, the rescue cuff was the traditional distal cuff of the double-cuff tourniquet. During session B, a single forearm cuff was used. When the volunteer experienced the same level of tourniquet pain, the rescue cuff was deflated and the study session ended. The tourniquet time for the rescue cuff, the visual analog scale (VAS) pain score, and the incidence and duration of side effects were recorded. RESULTS: The forearm rescue cuff was tolerated significantly longer than the arm rescue cuff (49 +/- 15 v 29 +/- 11 minutes, 95% confidence interval [CI] 7 to 32 minutes, P </=.005). When the forearm rescue cuff was used, VAS scores were lower and side effects were of shorter duration (6 +/- 5 v 15 +/- 7 minutes, P <.001). CONCLUSIONS: A forearm rescue cuff is better tolerated than an arm cuff double tourniquet during IVRA, allowing for longer tourniquet times. It is also associated with lower pain scores and shorter duration of local anesthetic side effects.

Adult↗

A prospective, randomized, controlled trial of forearm versus upper arm tourniquet tolerance.

This prospective, randomized, controlled trial studied the duration of upper and forearm tourniquet tolerance in 24 fit, healthy volunteers. Upper arm and forearm tourniquets were applied to either arm and inflated simultaneously. The time to request for deflation was recorded for each tourniquet. The mean tolerance for the upper arm tourniquet was 18 (range 10-26) min and for the forearm tourniquet was 25 (range 12-52) min. Under the conditions of this study, forearm tourniquets were tolerated for a mean of 7 min longer than upper arm tourniquets. The increase in tourniquet time afforded by a forearm tourniquet is clinically important in hand surgery performed under local anaesthetic.

Adult↗

[Differential diagnosis and therapy of post-traumatic limited forearm rotation].

Limited forearm rotation is an extremely disabling condition for patients. For forearm function, simultaneous rotation in the proximal and distal radioulnar joint is necessary, being connected by the radius and ulnar shaft. Any malalignment of these bony components as well as injuries to the stabilizing soft tissues will lead to an impaired function of the forearm joint. The combination of bony malalignment and joint instability is possible and must be recognized. Any chronic incongruency of the joints will lead to secondary arthrosis that allows only salvage procedures. Therefore, the underlying pathology of restricted forearm motion must be recognized and the original anatomy restored. Using clinical examples, the possible posttraumatic reasons for disturbed forearm rotation and the principle of anatomical reconstruction are presented.

Diagnosis, Differential↗

Nitric oxide biomarkers increase during exercise-induced vasodilation in the forearm.

The purpose of the study was to determine if exercise-induced vasodilation was associated with an increase in forearm plasma levels of nitric oxide (NO) biomarkers (NO2- + NO3- and L-citrulline). Twelve healthy subjects (27+/-6 yrs) performed incremental rhythmic forearm exercise with the nondominant hand for 6 min each at 15, 30 and 45% of maximal voluntary contraction (MVC). Forearm blood flow (FBF) was determined in the exercise arm using venous occlusion plethysmography. Blood samples were obtained from the antecubital vein of the exercise and nonexercise arms for the measurement of NO biomarkers. In the exercise arm, FBF increased by a mean of 150%, 335% and 585% above baseline at 15, 30 and 45% of MVC, respectively. (ANOVA, P= 0.0001). Venous plasma NO2- + NO3- levels increased from 24+/-4 micromol/L at baseline, to 29+/-5, 32+/-4 and 3+/-4 micromol/L (ANOVA, P = 0.0001). Venous plasma L-citrulline levels increased from 31+/-5 micromol/L at baseline to 58+/-10, 87+/-7 and 141+/-15 micromol/L (ANOVA, P = 0.0001). There was a linear relationship between FBF and venous plasma NO2- + NO3- (slope= 0.38+/-0.10, P=0.0007) and between L-citrulline, (slope= 5.1 +/-1.3, P = 0.0004). Venous plasma levels of NO2- + NO3- and L-citrulline in the nonexercise arm were unchanged. These results demonstrate that exercise-induced vasodilation in the forearm is associated with forearm plasma levels of NO2- + NO3- and L-citrulline, in vivo markers of NO production.

Adult↗

Direct closure of radial forearm free-flap donor sites by double-opposing rhomboid transposition flaps: case report.

A basic disadvantage of the radial forearm flap is the removal of skin from a functionally important and cosmetically exposed region. The donor site is conventionally repaired by skin grafting. However, this method is associated with complications of graft take and a poor aesthetic appearance. In this report, the authors describe a simple technique for direct closure of a distal forearm flap donor defect, using double-opposing rhomboid transposition flaps. This method is based on the existence of an oblique skin laxity in the distal forearm from the ulnar to the radial side, allowing a double-opposing local flap design. In a 32-year-old female patient, a 6- X 4-cm longitudinally-oriented elliptical skin defect of a radial forearm free flap was succesfully closed directly with the described technique without any complications. This method is a useful alternative for primary closure of small- to medium-sized distal forearm defects.

Adult↗

Oblique radial forearm reverse-flow flap.

A modifed design for the distally-based radial forearm flap is presented, in an oblique direction rather than longitudinally, based on the existence of skin laxity in the proximal forearm region. The skin paddle of the flap is designed in an oblique fashion pedicled on one of the proximal-row septocutaneous perforators, and elevated in the usual manner supplied by the distal radial artery. The oblique radial forearm flap thus created was successfully utilized for reconstruction of seven dorsal hand defects. Results showed that all the flaps could easily be transposed to the defect through a wide arc of rotation and all survived totally, with direct closure of the donor site in five cases, and significant reduction in size in the remaining two cases. It was concluded that the oblique design for the skin island of the reverse radial forearm flap could allow creation of a flap that has a smaller donor defect and yet presents a longer pedicle length, with a wider arc of rotation and better adaptation to a dorsal hand defect, than a conventional longitudinal-design radial forearm flap.

Adult↗

[Correction of forearm deformities in children with multiple cartilaginous osteochondromas].

AIM: Deformity of the forearm with shortening and bowing is common in children with multiple cartilaginous osteochondromas. The objective of this study was to evaluate the benefit of ulnar lengthening using an external fixateur in these patients. METHOD: 9 patients (10 cases) underwent surgery of the forearm between 1995 and 2001 and were evaluated using a standard protocol. The mean follow-up was 33.6 months, the mean age at operation 8.9 years. All patients were treated with ulnar lengthening, in 6 cases combined with an excision of the osteochondromas. RESULTS: Four out of ten patients did show an improvement in postoperative forearm rotation, two deteriorated and 4 presented unchanged. Wrist motion improved in 7 patients and remained unchanged in 3. The postoperative radial articular angle showed an improvement in 6, the carpal slip in 9 of the patients. The preoperative radial head dislocation in one patient remained unchanged postoperatively. CONCLUSION: The authors advocate this therapeutic concept for the correction of forearm deformity in multiple hereditary osteochondromas to prevent a progression of the deformity and to establish carpal stability. A significant improvement of forearm and wrist function could not be reached.

Bone Lengthening↗