Fiber architecture of the extensors of the hindlimb in semiterrestrial and arboreal guenons

Fiber architecture of the extensor musculature of the knee and ankle is examined in two African gueon species--the semiterrestrial Cercopithecus aethiops, and the arboreal C. ascanius. Using histologic and microscopic techniques to measure lengths of sarcomeres, the original lengths of muscle fasciculi and angles of pinnation in quadriceps femoris and triceps surae are reconstructed from direct measurements on cadavers. Calculations of reduced physiological cross-sectional area, mass/predicted effective tetanic tension, maximum excursion, and tendon length/fasciculus+tendon lengths are correlated to preferred locomotor modalities in the wild. For both species, greater morphological differences occur among the bellies of quadriceps femoris--rectus femoris, vastus intermedius, v. lateralis, and v. medialis--than among the bellies of triceps surae--gastrocnemius lateralis, g. medialis, plantaris, and soleus. With regard to quadriceps femoris, few differences occur between species. Interspecific differences in the triceps surae indicate (1) redirection of muscle force to accommodate arboreality in which the substrate is less than body width; (2) muscles more suited for velocity in the semiterrestrial vervets; and (3) muscles used more isotonically in vervets and more isometrically in red-tailed monkeys. The inherent flexibility of muscles may be preadaptive to a primary species shift in locomotor modality until the bony morphology is able to adapt through natural selection.     

Oxidation of acetate and octanoate and its relation to glucose metabolism in contracting porcine carotid artery

The oxidation of octanoate and acetate was measured in segments of porcine carotid arteries to ascertain whether the oxidation of exogenous fatty acid substrates (acetate and octanoate) is augmented during contraction induced by K(+)-depolarization. The oxidation of acetate increased from 7 +/- 1 to 14 +/- 2 nmol/min/g (P < 0.01) during sustained isometric contraction. Octanoate oxidation increased from 11 +/- 1 to 14 +/- 1 nmol/min/g (P < 0.05). The rate of oxidation of neither acetate nor octanoate was affected by the presence or absence of glucose either in resting or contracting arteries Acetate or octanoate oxidation could account for the majority of O2 consumption during contraction. Octanoate but not acetate inhibited glucose uptake and glycolysis in resting muscles. In contrast to augmented acetate and octanoate metabolism during contraction, there was a "down-regulation" of glucose metabolism in contracting muscles as evidenced by a decrease in the rate of glucose uptake, glycolysis and lactic acid production during sustained isometric contraction. Thus, contractile activation of vascular smooth muscle is associated with a shifting pattern of substrate utilization. Exogenous acetate or octanoate can serve as the primary oxidative substrate during sustained isometric contraction.     

The role of weakness of triceps surae muscles in astasia without abasia

OBJECTIVE: To investigate the role of weakness of the bilateral triceps surae muscles-the gastrocnemius and soleus muscles-in astasia without abasia and whether compensating for muscle weakness with ankle-foot orthoses improves this disability. DESIGN: Case-control study of clinical findings and before and after trial of ankle-foot orthoses. SETTING: Clinics of the departments of rehabilitation medicine of two university hospitals. PATIENTS: A stilts group consisting of 23 patients with astasia without abasia, and a non-stilts group without this phenomenon consisting of 12 patients with hereditary motor sensory neuropathy, 15 patients with lumbosacral spondylotic radiculopathy or spondylolisthesis, and 20 healthy volunteers. MAIN OUTCOME MEASURE: Clinical findings of the stilts and non-stilts groups were compared and the sensitivity and specificity of each clinical finding was calculated. The length of the centre of foot pressure (COP) while standing was measured in a bilateral below knee amputee and 16 consecutive patients in the stilts group with and without ankle-foot orthoses. RESULTS: Weakness of the triceps surae muscles was the only finding that differed significantly between the two groups and was both sensitive and specific. The amputee was unable to stand in place without dorsiflexion bumpers, which functioned similarly to the triceps surae muscle. Bilateral ankle-foot orthoses improved the COPs of 14 out of 16 patients. CONCLUSION: The main cause of astasia without abasia is weakness of the triceps surae muscles, and this disability is improved by bilateral ankle-foot orthoses.     

A comparison of the contractile properties of the muscles of the lower extremities in man

The physiological features of two antagonistic muscle groups, the dorsiflexors and plantar flexors of the ankle, have been compared in 11 healthy subjects aged 15-17 years (+/- SE; 16 +/- 1.2 years). Contractile properties of plantar flexors of the foot, namely of tibialis anterior (TA) and extensors triceps surae (TS) have been estimated by mechanical parameters of voluntary and electrically evoked contractions. All test subjects exhibited tolerance to supramaximal force of electric stimulation of n. tibialis and n. peroneus profundus at a frequency of 150 impulses.s-1 (for TS) and 150 impulses.s-1 and 250 impulses.s-1 (for TA). TA displayed high velocity and force-velocity properties (p < 0.05-0.001); TS had high force parameters (p < 0.05-0.01). The magnitude of force deficiency observed during voluntary contraction of these muscles is lower in TA and higher in TS (p < 0.05). The results permit supposing that differences in contractile properties of the muscles under study depend on a various specific contribution of peripheral and CNS factors.     

Somatostatin-stimulated growth hormone-releasing factor secretion in vitro is modified by fetal ethanol exposure

1. The mechanism of neurogenic regulation of skeletal muscle circulation was studied in the hindlimb of anaesthetized rats in vivo. Regional blood flow (RBF) of the hindlimb was recorded with a pulsed Doppler flow probe positioned in the iliac artery. 2. A short period (1 min) of sciatic nerve stimulation at 10 Hz caused a sustained increase in RBF (from 2.0 +/- 0.2 to 3.7 +/- 0.2 kHz at the peak), but no appreciable change in either MBP or HR, suggesting that the nerve stimulation produced local vasodilatation of the peripheral vasculature. The hyperaemic response reached a peak within 15 s and characteristically remained above the basal level for more than 5 min after the cessation of nerve stimulation. The response was regarded as a secondary response brought about by the contraction of skeletal muscles since (+)-tubocurarine (0.73 micromol kg(-1), i.a.) almost abolished it. 3. Lignocaine (43 micromol kg(-1), i.a.) and capsaicin (0.33 micromol kg(-1), i.a.) significantly suppressed the hyperaemic response to skeletal muscle contraction, suggesting that capsaicin-sensitive sensory nerves contribute to the hyperaemia. In contrast, an inhibitor of NO synthase, N(omega)-nitro-L-arginine methyl ester (1 micromol kg(-1) min(-1), i.v.), did not affect the hyperaemic response. 4. Serum levels of calcitonin gene-related peptide (CGRP) in iliac venous effluent significantly increased from 51 +/- 4 to 77 +/- 5 fmol ml(-1) during the hyperaemic response to skeletal muscle contraction. A bolus injection of CGRP (300 pmol kg(-1), i.a.) induced a long-lasting increase in RBF of the hindlimb. Moreover, CGRP(8-37) (100 nmol kg(-1) min(-1), i.v.), a specific CGRP1 receptor antagonist, significantly suppressed the hyperaemic response, especially the sustained phase of the response which was almost abolished by this antagonist. 5. These results suggest that CGRP, which is released from peripheral endings of capsaicin-sensitive sensory nerves, partly mediates the hyperaemia evoked by skeletal muscle contraction of the rat hindlimb.     

Interactions between vestibular and proprioceptive inputs triggering and modulating human balance-correcting responses differ across muscles

Interactions between proprioceptive and vestibular inputs contributing to the generation of balance corrections may vary across muscles depending on the availability of sensory information at centres initiating and modulating muscle synergies, and the efficacy with which the muscle action can prevent a fall. Information which is not available from one sensory system may be obtained by switching to another. Alternatively, interactions between sensory systems and the muscle to which this interaction is targeted may be fixed during neural development and not switchable. To investigate these different concepts, balance corrections with three different sets of proprioceptive trigger signals were examined under eyes-open and eyes-closed conditions in the muscles of normal subjects and compared with those of subjects with bilateral peripheral vestibular loss. The different sets of early proprioceptive inputs were obtained by employing three combinations of support surface rotation and translation, for which ankle inputs were nulled, normal or enhanced, the knees were either locked or in flexion, and the trunk was either in flexion or extension. Three types of proprioceptive and vestibulospinal interactions were identified in muscles responses. These interactions were typified by the responses of triceps surae, quadriceps, and paraspinal muscles. The amplitudes of stretch responses at 50 ms after the onset of ankle flexion in triceps surae muscles were related to the velocity of ankle stretch. The amplitude of balance-correcting responses at 100 ms corresponded more with stretch of the biarticular gastrocnemius when the knee was re-extended at 60 ms. Absent stretch reflexes at 50 ms in triceps surae with nulled ankle inputs caused a minor, 12-ms delay in the onset of balance-correcting responses in triceps surae muscles. Vestibular loss caused no change in the amplitude of balance-correcting responses, but a negligible decrease in onset latency in triceps surae even with nulled ankle inputs. Stretch responses in quadriceps at 80 ms increased with the velocity of knee flexion but were overall lower in amplitude in vestibular loss subjects. Balance-correcting responses in quadriceps had amplitudes which were related to the directions of initial trunk movements, were still present when knee inputs were negligible and were also altered after vestibular loss. Stretch and unloading responses in paraspinals at 80 ms were consistent with the direction of initial trunk flexion and extension. Subsequent balance-correcting responses in paraspinals were delayed 20 ms in onset and altered in amplitude by vestibular loss. The changes in the amplitudes of ankle (tibialis anterior), knee (quadriceps) and trunk (paraspinal) muscle responses with vestibular loss affected the amplitudes and timing of trunk angular velocities, requiring increased stabilizing tibialis anterior, paraspinal and trapezius responses post 240 ms as these subjects attempted to remain upright. The results suggest that trunk inputs provide an ideal candidate for triggering balance corrections as these would still be present when vestibular, ankle and knee inputs are absent. The disparity between the amplitudes of stretch reflex and automatic balance-correcting responses in triceps surae and the insignificant alteration in the timing of balance-correcting responses in these muscles with nulled ankle inputs indicates that ankle inputs do not trigger balance corrections. Furthermore, modulation of balance corrections normally performed by vestibular inputs in some but not all muscles is not achieved by switching to another sensory system on vestibular loss. We postulate that a confluence of trunk and upper-leg proprioceptive input establishes the basic timing of automatic, triggered balance corrections which is then preferentially weighted by vestibular modulation in muscles that prevent falling. (ABSTRACT TRUNCATED)     

Distinct patterns of motor unit behavior during muscle spasms in spinal cord injured subjects

Surface electromyograms (EMG) and force were recorded during repeated involuntary spasms of paralyzed triceps surae muscles of four men with chronic cervical spinal cord injury. The firing rates of 78 medial gastrocnemius (MG) motor units also were recorded intramuscularly with tungsten microelectrodes. Spasms typically involved a relatively rapid rise, then a more gradual fall in triceps surae EMG and torque. Motor unit firing rates either increased and then decreased with the spasm intensity (54%) or were relatively constant (26%), firing mainly at 2-10 Hz. The remaining units (20%) produced trains that included one or several doublets. Mean peak spasm firing rates were 18 +/- 9 Hz (mean +/- SD) for rate modulated units and 11 +/- 10 Hz for units with little or no rate modulation. Some motor units fired at rates comparable with those recorded previously during maximum voluntary contractions performed by intact subjects. Others fired at rates below the minimum usually seen when normal units are first recruited (< 6 Hz). Doublets (interspike interval < 10 ms) often repeated every 123-333 ms, or were interspersed in trains firing at low steady rates (< 11 Hz). This study shows that rate coding for many motor units appears to be similar whether descending motor input is intact or whether it has been reduced severely by spinal cord injury. In contrast, rate modulation in other units appears to depend mainly on voluntary motor commands.     

Nitric oxide synthesis inhibition: the effect on rabbit pyloric muscle

The relaxation mechanism of the pyloric smooth muscle is largely dependent on a nonadrenergic noncholinergic (NANC) inhibitory innervation mediated in part by nitric oxide (NO). The aim of the present study was to investigate the effect of NO antagonists on the contractility of the pyloric smooth muscle. In the clinical trial, 10 anesthetized experimental rabbits were infused intraarterially with the NO synthesis inhibitor N-nitro-L-arginine (L-NNA), at a concentration of 10(-4) mol/L; 10 controls received normal saline intraarterially. Pyloric contractility was assessed by balloon manometry. L-NNA infusion produced a dose-dependent increase in the frequency of the pyloric contraction. The maximal increase in frequency occurred during the slow L-NNA infusion rate of 146 ng/min (baseline-adjusted frequencies of experimental v control: 1.267 +/- 0.389 v 0.632 +/- 0.375; P = .001). The increased frequency level was sustained over the subsequent fast infusion rate of 292 ng/min (experimental v control: 1.362 +/- 0.604 v 0.704 +/- 0.579; P = .022). Both the duration and the amplitude of the pyloric contractions were not affected by the L-NNA infusion. These findings suggest that blockage of the L-arginine-NO pathway may have resulted in inhibition of the NANC-induced gastric muscle and relaxation of the pyloric sphincter. The authors speculate that the decreased NO production may be responsible for the sustained contraction of the pyloric smooth muscle with secondary hypertrophy, characteristic of hypertrophic pyloric stenosis.     

ORG 9487 neuromuscular block at the adductor pollicis and the laryngeal adductor muscles in humans

BACKGROUND: ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis. METHODS: In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 microg/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group). RESULTS: Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P < 0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle. CONCLUSIONS: ORG 9487 has a rapid onset of action at the laryngeal adductor and the adductor pollicis muscles. Onset and duration of action are faster at the vocal cords than at the adductor pollicis muscle. However, the maximum block obtained at the laryngeal muscles was less than at the adductor pollicis, regardless of the dose of ORG 9487.     

Effect of theophylline on substrate metabolism during exercise

We tested the hypothesis that adenosine is involved in regulating substrate metabolism during exercise. Seven trained cyclists were studied during 30 minutes of exercise at approximately 75% maximal oxygen uptake (VO2max). Lipid metabolism was evaluated by infusing [2H5]glycerol and [1-13C]palmitate, and glucose kinetics were evaluated by infusing [6,6-2H]glucose. Fat and carbohydrate oxidation were also measured by indirect calorimetry. The same subjects performed two identical exercise tests, but in one trial theophylline, a potent adenosine receptor antagonist, was infused for 1 hour before and throughout exercise. Theophylline did not increase whole-body lipolysis (glycerol rate of appearance [Ra]) or free fatty acid (FFA) release during exercise, but fat oxidation was lower than control values (9.5 +/- 3.0 v 18.0 +/- 4.2 micromol x min(-1) x kg(-1), P < .01). Glucose Ra was not affected by theophylline infusion, but glucose uptake was lower (31.6 +/- 4.1 v 40.4 +/- 5.0 micromol x min(-1) x kg(-1), P < .05) and glucose concentration was higher (6.4 +/- 0.6 v 5.8 +/- 0.4 mmol/L, P < .05) than in the control trial. Total carbohydrate oxidation (302.3 +/- 26.2 v 265.5 +/- 11.7 micromol x min(-1) x kg(-1), P < .06), estimated muscle glycogenolysis (270.7 +/- 23.1 v 225.1 +/- 9.7 micromol x min(-1) x kg(-1), P < .05), and plasma lactate concentration (7.9 +/- 1.6 v 5.9 +/- 1.1 mmol/L, P < .001) were also higher during the theophylline trial. These data suggest that adenosine may play a role in stimulating glucose uptake and restraining glycogenolysis but not in limiting lipolysis during exercise.     

Role of microtubules in the contractile dysfunction of hypertrophied myocardium

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.     

Inhibition of Ca2+ release in rat atrophied gastrocnemius muscle

Contractile parameters of a twitch contraction and changes in these parameters during repetitive stimulation are modified by muscle atrophy induced by tetrodotoxin (TTX). These altered parameters included developed tension (DT), contraction time (tC), half-relaxation time (tR, 1/2), average rate of force development (DT tC-1) and peak rate of relaxation (DTdtmin-1). These modifications may be related to different Ca2+ concentration transients in the myoplasm during muscle stimulation. We have used dantrolene sodium (DS) in TTX-treated rat gastrocnemius muscle to test this hypothesis. In situ isometric contractile responses of rat gastrocnemius muscle during repetitive stimulation at 10 Hz were analysed before and after administration of DS. After DS administration, twitch amplitude, tC, tR, 1/2 and DT tC-1 decreased and DTdtmin-1 relative to DT increased in atrophied muscle. During repetitive stimulation, a progressive enhancement developed tension (staircase) was absent in atrophied muscle, but DT increased to 171 +/- 4%, presenting a staircase response after DS treatment. This potentiation was accompanied by an increase in DT tC-1 to 175.6 +/- 7%. Inhibition of Ca2+ release in atrophied muscle resulted in twitch contractile parameters and contractile responses to 10 Hz stimulation that were similar, in many respects, to those responses in control (non-atrophied) muscles.     

Antithrombotic effects of MK-0852, a platelet fibrinogen receptor antagonist, in canine models of thrombosis

The antiaggregatory and antithrombotic actions of MK-0852, a cyclic heptapeptide antagonist of the platelet GP IIb/IIIa, were evaluated in a variety of canine models. In vitro, MK-0852 inhibited the aggregation of canine platelet-rich plasma induced by 10 microM ADP in the presence of 1 microM epinephrine with an IC50 value of 0.10 microM. The i.v. infusion of 1.0 and 3.0 micrograms/kg/min MK-0852 to anesthetized dogs significantly inhibited ex vivo platelet aggregation responses to ADP and collagen, with the 3.0 micrograms/kg/min infusion completely inhibiting ex vivo aggregation responses to both agonists. The i.v. administrations of 100 and 300 micrograms/kg MK-0852 suppressed platelet-dependent cyclic flow reductions in stenosed canine left circumflex (LCX) coronary artery for periods of 24 +/- 3 and 64 +/- 4 min, respectively. In a canine model of copper coil-induced femoral arterial thrombosis, i.v. MK-0852 (100 micrograms/kg + 1 microgram/kg/min), initiated 15 min before coil placement, reduced the incidence of occlusive thrombosis during the 45-min post-coil time period of continued therapy (1/5 MK-0852 vs. 7/7 saline; P < .01). MK-0852 was administered as an adjunctive therapy with tPA to evaluate its effects on thrombolysis after copper coil-induced femoral arterial thrombus formation. MK-0852 (i.v.; 100 micrograms/kg + 1 microgram/kg/min), initiated 15 min before tPA, reduced the incidence of post-thrombolysis reocclusion. During the 60-min period of continued drug infusion after the termination of tPA, 0 of 5 animals receiving MK-0852 reoccluded vs. 7/8 saline (P < .01). In a canine model of electrically induced LCX coronary artery thrombosis, i.v. MK-0852 (100 micrograms/kg + 3 micrograms/kg/min), initiated 15 min before the initiation of electrical injury, prevented occlusive thrombosis in 4 of 6 preparations despite the continued electrical stimulation of the vessel for 180 min. Thrombotic occlusion was delayed in the remaining two preparations (99 and 100 min), compared with occlusion in 4 of 4 saline-treated preparations (69.3 +/- 6.3 min). When administered as an adjunct to thrombolytic agents for lysis of electrically induced LCX coronary artery thrombi, i.v. MK-0852 (300 micrograms/kg + 3 micrograms/kg/min), initiated 15 min before tPA or streptokinase, both increased the incidence of reperfusion (tPA: 8/8 MK-0852 vs. 3/8 saline; streptokinase: 5/8 MK-0852 vs. 2/8 saline) and accelerated reperfusion. The incidence of reocclusion during continued adjunctive therapy was reduced.(ABSTRACT TRUNCATED AT 400 WORDS)     

The ETA receptor antagonist, BMS-182874, reduces acute hypoxic pulmonary hypertension in pigs in vivo

OBJECTIVE: Elevated levels of the potent vasoactive peptide endothelin (ET), have been found in pathophysiological conditions associated with pulmonary hypertension. In this study, we have investigated the effects of the ETA receptor antagonist, BMS-182874, on hypoxic pulmonary hypertension in pigs. METHODS: Pigs were subjected to acute, intermittent 15-min periods of hypoxia (FiO2 0.1). Following a first hypoxia establishing hypoxic baseline values, vehicle or BMS-182874 (10 or 30 mg/kg) was administered i.v. before a second hypoxic period. In separate groups of animals, the effects of the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA) in combination with BMS-182874 (10 mg) during repeated hypoxia were investigated. The ET-1-blocking properties of BMS-182874 were studied in vivo by infusion of ET-1 during normoxia and in vitro using isolated porcine pulmonary arteries. RESULTS: The hypoxia-evoked increase in mean pulmonary artery pressure was reduced by administration of BMS-182874 (10 mg/kg i.v.; from 42 +/- 8 to 34 +/- 4 mmHg, P < 0.05 and 30 mg/kg i.v.; from 38 +/- 4 to 30 +/- 5 mmHg, P < 0.05). In addition, BMS-182874 at 30 mg/kg reduced the pulmonary vascular resistance during hypoxia (from 7.4 +/- 1.5 to 5.3 +/- 1.1 mmHg.min.l-1 P < 0.05). The hemodynamic response to repeated hypoxia was reproducible in control animals and unaffected by the cyclo-oxygenase inhibitor diclophenac (3 mg/kg). Infusion of L-NNA alone resulted in an augmented pulmonary vasoconstriction during hypoxia; pulmonary arterial pressure from 35 +/- 6 to 43 +/- 9 mmHg; P < 0.05 and vascular resistance from 7.2 +/- 1.1 to 9.9 +/- 1.8 mmHg.min.l-1; P < 0.05. L-NNA in combination with BMS-182874 (10 mg/kg) resulted in a hypoxic pulmonary vasoconstriction of similar magnitude as hypoxic baseline. In addition, BMS-182874 reduced the hemodynamic response to ET-1 in normoxic pigs and competitively antagonized the vasoconstrictor effect of ET-1 in isolated porcine pulmonary arteries. CONCLUSIONS: The non-peptide, selective ETA receptor antagonist, BMS-182874, reduces hypoxic pulmonary vasoconstriction in pigs. The reduction in pulmonary vascular response to hypoxia following BMS-182874 is at least partly independent of nitric oxide.     

Rat hindlimb muscle blood flow during level and downhill locomotion

During eccentrically biased exercise (e.g., downhill locomotion), whole body oxygen consumption and blood lactate concentrations are lower than during level locomotion. These general systemic measurements indicate that muscle metabolism is lower during downhill exercise. This study was designed to test the hypothesis that hindlimb muscle blood flow is correspondingly lower during downhill vs. level exercise. Muscle blood flow (determined by using radioactive microspheres) was measured in rats after 15 min of treadmill exercise at 15 m/min on the level (L, 0 degrees) or downhill (D, -17 degrees). Blood flow to ankle extensor muscles was either lower (e.g., white gastrocnemius muscle: D, 9 +/- 2; L, 15 +/- 1 ml. min-1. 100 g-1) or not different (e.g., soleus muscle: D, 250 +/- 35; L, 230 +/- 21 ml. min-1. 100 g-1) in downhill vs. level exercise. In contrast, blood flow to ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 +/- 5; L, 31 +/- 6 ml. min-1. 100 g-1) during downhill vs. level exercise. When individual extensor and flexor muscle flows were summed, total flow to the leg was lower during downhill exercise (D, 3.24 +/- 0.08; L, 3.47 +/- 0. 05 ml/min). These data indicate that muscle blood flow and metabolism are lower during eccentrically biased exercise but are not uniformly reduced in all active muscles; i.e., flows are equivalent in several ankle extensor muscles and higher in ankle flexor muscles.     

The neurotrophic analogue of ACTH(4-9) reduces the perineuronal microglial reaction after rat facial nerve crush

Rats bled to a severe condition of volume-controlled hemorrhagic shock were randomly assigned to one of the following treatments: (1) saline, 1 ml/kg i.v.; (2) saline, 0.2 ml/kg per min i.v. for 10 min; (3) ACTH-(1-24), 160 micrograms/kg i.v.; 4) methylprednisolone, 40 mg/kg i.v.; (5) methylprednisolone, 80 mg/kg i.v.; (6) aprotinin, 10,000 KIU/kg i.v.; (7) norepinephrine, 5 micrograms/kg per min i.v. for 10 min; (8) norepinephrine, 10 micrograms/kg per min i.v. for 10 min. All rats treated with saline or with either of the two doses of methylprednisolone, and half of the rats treated with aprotinin, died within the subsequent 2 h. On the other hand, rats treated with norepinephrine, at either dose, or with ACTH-(1-24) were all still alive 2 h later, a similar improvement in cardiovascular and respiratory parameters being obtained with the two treatments. The effect of ACTH on mean arterial pressure was however more sustained throughout the observation period. These results further support the potential usefulness of ACTH-(1-24) as first-aid treatment in cases of severe blood losses.     

Effect of radial shortening on muscle length and moment arms of the wrist flexors and extensors

Manual muscle test scores (MMTS) and maximum voluntary contraction (MVC) force measurements were made from triceps brachii muscles of 70 individuals with chronic cervical spinal cord injury (SCI). Both MMTS and strength assessments showed that asymmetrical motor deficits were common. Muscles with MMTS of 3 generated an average of nine percent MVC force produced by control muscles. In this SCI population, little residual voluntary force is apparently needed for triceps brachii to work against gravity. Only 24 percent of muscles tested had this strength, however, indicating the need to develop strategies to alleviate this muscle weakness. MMTS and force were related positively but each MMTS was not associated with a unique force range. MVC force generating capacity is therefore only one factor that determines whether or not a muscle can work with or against gravity and against resistance.     

Glucose-induced changes in renal haemodynamics in proteinuric type 1 (insulin-dependent) diabetic patients: inhibition by acetylsalicilic acid infusion

The effect of hyperglycaemia on renal function in diabetic nephropathy remains poorly understood. We investigated the renal haemodynamic response to an acute plasma glucose rise from sustained euglycaemia to sustained hyperglycaemia in eight persistently proteinuric Type 1 (insulin-dependent) diabetic patients. Studies were performed in a double-blind cross-over manner after i.v. injection of 450 mg lysine acetylsalicilate (equivalent to 250 mg acetylsalicilic acid) or equal volume of 0.9% NaCl (isotonic saline). In the isotonic saline experiments hyperglycaemia produced a significant rise, by approximately 35%, in glomerular filtration rate in all patients from 41.5 +/- 5.2 to 55 +/- 6 ml.min-1.1.73 m-2 (p < 0.005) and an increase in sodium paraminohippurate clearance from 178 +/- 22.7 to 220 +/- 20.0 ml.min-1.1.73 m-2 (p < 0.05). These changes took place within the first 30 min of glucose infusion and were maintained for a 90 min hyperglycaemic period. Filtration fraction did not change significantly. Infusion of lysine acetylsalicilate lowered baseline glomerular filtration rate (isotonic saline vs lysine acetylsalicilate 41.5 +/- 5.2 vs 30.0 +/- 5.7 ml.min-1.1.73 m-2; p < 0.05) and significantly blunted the rise in glomerular filtration rate during hyperglycaemia (glomerular filtration rate increment: saline vs lysine acetylsalicilate: 13.6 +/- 2.8 vs 5.3 +/- 1.8 ml.min-1.1.73 m-2; p < 0.005). The effects on renal plasma flow were similarly blunted. In five additional patients, time- and volume-controlled isotonic saline experiments during sustained euglycaemia showed no significant changes in glomerular filtration rate and sodium paraminohippurate clearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contractile properties of aged avian muscle after stretch-overload

The effects of ageing on muscle contractile adaptations to stretch-overload was examined in the anterior latissimus dorsi (ALD) muscle of 12 old (90 weeks of age) and 12 young adult (10 weeks of age) Japanese quails. A weight corresponding to 12% of the birds' body weight was attached to one wing for 30 days, while the contralateral wing served as the intra-animal control. In vitro contractile measurements were made at 25 degrees C by indirect stimulation of the ALD by its nerve (pulse 0.2 ms). Compared with young adult twitch characteristics, aged muscles had significantly greater contraction time (149 +/- 9 ms vs. 174 +/- 16 ms). Stretch-overload increased contraction time to 162 +/- 7 ms in young muscles and 215 +/- 14 ms in old muscles. Ageing and overload resulted in a greater fusing of twitches at stimulation frequencies of 5 and 10 Hz which resulted in a leftward shift of the force-frequency curve at these frequencies, relative to young adult control muscles. Maximal shortening velocity (Vmax) decreased from 2.6 +/- 0.3 to 1.2 +/- 0.1 muscle lengths/s in young muscles after overload. Vmax in old control muscles was similar to young muscles after stretch, but stretch further decreased Vmax in old muscles to 0.8 muscle lengths/s. Maximal tetanic force and specific force were similar in young and old muscles, both before and after stretch. These data indicate that ageing induces a slowing of both twitch contractile characteristics and shortening velocity in the ALD, without affecting maximal force capabilities.