Stimulation Of Sciatic Nerve Research Articles

The effects of cortical stimulation, anesthesia and recording site on somatosensory evoked potentials in the rat

The purpose of this study was to standardize the method of spinal cord monitoring with evoked potentials in the rat. Seventeen male Wistar rats were anesthetized with α-chloralose and urethane. Somatosensory evoked potential (SEP) and cerebellar evoked potential (CEP) following sciatic nerve stimulation were mapped at different time points after induction of anesthesia. SEP peaks at latencies of 13–18 ms (P13, N18) were localized to an extremely small area over the sensory cortex. In contrasts, a negative peak of the SEP at 11 ms (N11) and the CEP were widely distributed over the cerebral or cerebellar surface. Anesthesia significantly influenced the cortical components of the SEP. In 10 rats, MEP or posterior fossa evoked potential (PFEP) following stimulation of the sensorimotor or cerebellar cortices respectively, were recorded at T9. Stimulation of different points produced little change on the waveforms of the MEP or PFEP. Successive recordings of MEP and SEP revealed that the P13-N18 complex of the SEP was markedly suppressed after MEP recordings were made. In conclusion, this study identified several factors which alter SEP waveforms in the rat including location of recording, anesthesia and sequence with respect to MEP recording. MEP by stimulation of the same sensory cortex as SEP recordings should not be used for concurrent monitoring, since cortical stimulation will change the waveforms of the SEP.

The effects of cortical stimulation, anesthesia and recording site on somatosensory evoked potentials in the rat.

The purpose of this study was to standardize the method of spinal cord monitoring with evoked potentials in the rat. Seventeen male Wistar rats were anesthetized with alpha-chloralose and urethane. Somatosensory evoked potential (SEP) and cerebellar evoked potential (CEP) following sciatic nerve stimulation were mapped at different time points after induction of anesthesia. SEP peaks at latencies of 13-18 ms (P13, N18) were localized to an extremely small area over the sensory cortex. In contrasts, a negative peak of the SEP at 11 ms (N11) and the CEP were widely distributed over the cerebral or cerebellar surface. Anesthesia significantly influenced the cortical components of the SEP. In 10 rats, MEP or posterior fossa evoked potential (PFEP) following stimulation of the sensorimotor or cerebellar cortices respectively, were recorded at T9. Stimulation of different points produced little change on the waveforms of the MEP or PFEP. Successive recordings of MEP and SEP revealed that the P13-N18 complex of the SEP was markedly suppressed after MEP recordings were made. In conclusion, this study identified several factors which alter SEP waveforms in the rat including location of recording, anesthesia and sequence with respect to MEP recording. MEP by stimulation of the same sensory cortex as SEP recordings should not be used for concurrent monitoring, since cortical stimulation will change the waveforms of the SEP.

Increased oxidative and delayed glycogenolytic ATP synthesis in exercising skeletal muscle of obese (insulin-resistant) Zucker rats.

1. To examine metabolic correlates of insulin resistance in skeletal muscle, we used 31P magnetic resonance spectroscopy to study glycogenolytic and oxidative ATP synthesis in leg muscle of lean and obese Zucker rats in vivo during 6 min sciatic nerve stimulation at 2 Hz. 2. The water content of resting muscle was reduced by 21 +/- 7% in obese (insulin-resistant) animals compared with lean animals, whereas the lipid content was increased by 140 +/- 70%. These results suggest that intracellular water content was reduced by 17% in obese animals. 3. During exercise, although twitch tensions were not significantly different in the two groups, rates of total ATP synthesis (expressed per litre of intracellular water) were 48 +/- 20% higher in obese animals, suggesting a 50 +/- 8% reduction in intrinsic "metabolic efficiency'. Changes in phosphocreatine and ADP concentration were significantly greater in obese animals than in lean animals, whereas changes in intracellular pH did not differ. 4. These results imply that oxidative ATP synthesis during exercise is activated earlier in obese animals than in lean animals. This difference was not fully accounted for by the greater increase in the concentration of the mitochondrial activating signal ADP. Neither the post-exercise recovery kinetics of phosphocreatine nor the muscle content of the mitochondrial marker enzyme citrate synthase was significantly different in the two groups. The increased oxidative ATP synthesis in exercise must therefore be due to altered kinetics of mitochondrial activation by signals other than ADP. 5. Thus, the insulin-resistant muscle of obese animals may compensate for its decreased efficiency (and consequent increased need for ATP) by increased reliance on oxidative ATP synthesis.

Processing of vestibular and other inputs by the caudal ventrolateral medullary reticular formation.

Lesions of the lateral medullary reticular formation caudal to the obex abolish vestibulosympathetic and somatosympathetic responses; this area also contains neurons that mediate baroreceptor reflexes. Recordings were made from neurons in the caudal medullary reticular formation of cats that were decerebrate or anesthetized using alpha-chloralose-urethan to determine whether common neurons responded to electrical stimulation of vestibular and hindlimb afferents and had cardiac-related (i.e., baroreceptor) inputs. Many neurons in the ventrolateral portion of the caudal reticular formation received labyrinthine inputs, and they were interspersed with neurons that received baroreceptor signals. However, virtually none of the units received convergent baroreceptor and vestibular inputs, suggesting that separate pathways from the caudal ventrolateral medulla mediate baroreceptor and vestibulosympathetic reflexes. Furthermore, the neurons that received labyrinthine signals could not be antidromically activated from electrodes inserted into the rostral ventrolateral medulla, which is known to mediate vestibulosympathetic responses; thus an indirect pathway must convey vestibular inputs from the caudal to rostral medullary reticular formation. Over 75% of both neurons with baroreceptor inputs and cells with vestibular signals responded to sciatic nerve stimulation, suggesting that more than one pathway from the caudal medulla may mediate somatosympathetic responses.

Regulation of oxidative and glycogenolytic ATP synthesis in exercising rat skeletal muscle studied by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy measurements of pH and the concentrations of orthophosphate and phosphocreatine were used to estimate rates of glycogenolytic and oxidative ATP synthesis in rat leg muscle during 6 min sciatic nerve stimulation at different rates (1-4 Hz). To study the regulation of glycogenolysis during exercise, the apparent 'glycogenolytic capacity' (L(MAX)) was calculated from glycogenolytic ATP synthesis rate and orthophosphate concentration as a measure of the Ca2+-dependent activation of glycogen phosphorylase. This was found to be proportional to the total ATP synthesis rate (F), and to decline with time; expressed relative to total ATP turnover rate as L(MAX)/F, its initial value was 2.9+/-0.6, declining with half-time 1.4+/-0.4 min. The apparent 'mitochondrial capacity' (Q(MAX)), calculated from oxidative ATP synthesis rate and [ADP], was independent of ATP turnover rate, but increased with half-time 0.8+/-0.1 min to 29+/-2 mmol kg(-1) min(-1): thus [ADP] was the predominant but not the only influence on oxidative ATP synthesis. Numerical simulation shows that time-dependent changes in L(MAX)/F exert a strong influence on pH and on the concentrations of phosphocreatine and ADP.

Pharmacodynamic analysis of contractile potentiation by cholinesterase inhibitors in rats.

Pharmacological profiles of four cholinesterase (ChE) inhibitors: edrophonium, pyridostigmine, neostigmine, and ambenonium after to administration to rats were analyzed. A pharmacodynamic model was developed by considering acetylcholinesterase (AChE) inhibition, direct antagonism to the nicotinic receptor, and desensitization of the nicotinic receptor. Pharmacokinetics of these drugs are dose-independent and have similar volumes of distribution at steady state (0.4-0.6 L/kg various doses). The t1/2 increases in the order of neostigmine, edrophonium, pyridostigmine, and ambenonium. Inhibitory constants of ChE inhibitors to bovine erythrocyte AChE determined in vitro were 2019, 276, 26, and 3.7 nM for edrophonium, pyridostigmine, neostigmine, and ambenonium, respectively. The effect of ChE inhibitor was monitored as the increase of developed tension of triceps muscle induced by sciatic nerve stimulation. The maximum value of contractile tension after i.v. administration decreased at high doses of each drug and the dose-response curves were biphasic. Time courses of plasma concentration and contractile muscle tension were modeled to estimate the association/dissociation rate constants to AChE and the nicotinic receptor, desensitization rate constant of receptor and the dissociation constant of acetylcholine (ACh) to nicotinic receptor/basal acetylcholine level ratio (Kd/ACh0). The estimated Kd/ACh0 values were not dependent on the drug. A significant correlation between inhibitory constants of ChE inhibitors to AChE estimated by in vivo pharmacodynamic analysis and those determined by an in vitro enzyme kinetic study was shown, while the relationship between dissociation constants to nicotinic receptor estimated by in vivo pharmacodynamic analysis and those measured by an in vitro binding study was not clear. Other process such as desensitisization induced by endogenous ACh diffusion rate of drugs into the synaptic cleft, action of presynaptic receptors, etc., might contribute to the dose-effect relationship of ChE inhibitors.

Desflurane Attenuates the Somatosympathetic Reflex in Rats

Arterial blood pressure and heart rate changes after afferent somatic sensory nerve stimulation are termed the "somatosympathetic reflex" (SSR). Inhibition of the SSR may partially represent an antinociceptive action. This investigation examined the actions of the volatile anesthetic, desflurane, on the SSR evoked by peripheral nerve stimulation. Rats anesthetized with alpha-chloralose (50 mg/kg) and urethane (500 mg/kg) were mechanically ventilated and cannulated with arterial and venous catheters for monitoring arterial pressure and for fluid administration, respectively. The sciatic (n = 7) or tibial (n = 6) nerves were isolated and stimulated at one, two, and four times the voltage threshold required to elicit a change in systemic hemodynamics. These cardiovascular responses were recorded before, during, and after varying concentrations of desflurane, 1.8% (0.25 minimum alveolar anesthetic concentration [MAC]), 3.6% (0.5 MAC), 7.2% (1.0 MAC), and 10.8% (1.5 MAC). Desflurane decreased arterial pressure at 1.0 and 1.5 MAC and heart rate (at more than 0.5 MAC) compared to baseline levels. Tibial nerve stimulation decreased mean arterial pressure (MAP) with no consistent changes in heart rate. Desflurane significantly attenuated this depressor response to tibial nerve stimulation (MAP decrease: control; -20 +/- 2 mm Hg versus 1.0 MAC desflurane; -6 +/- 4 mm Hg). The increases in MAP after sciatic nerve stimulation were also significantly inhibited by increasing concentrations of desflurane. At more than 0.5 MAC desflurane, the pressor response to sciatic nerve stimulation was significantly converted to a depressor response in four of seven rats (MAP: control; increase 24 +/- 2 mm Hg versus 1.0 MAC desflurane; decrease -2 +/- 4 mm Hg). Sciatic nerve stimulation also elicited increases in heart rate which were significantly attenuated by desflurane (control; 37 +/- 6 bpm versus 1.5 MAC desflurane; 0 +/- 2 bpm). These findings demonstrate that desflurane produces dose-dependent cardiovascular depression in rats and, despite previous reports of sympathoexcitation, desflurane significantly attenuated both excitatory and inhibitory types of SSR. The results of this study also support a potential antinociceptive action for this anesthetic.

A malonyl-CoA fuel sensing mechanism in muscle: effects of insulin, glucose and denervation: A. K. Saha, T. G. Kurowski, N. B. Ruderman.Am J Physiol 1995; 269: E283–E289

Increases in the concentration of malonyl-CoA in skeletal musclehave been observed in the KKA Y mouse, an obese rodent with high plasma insulin and glucose levels (1). To assess whether insulin and glucose directly regulate malonyl-CoA in muscle, soleus muscles from young rats were incubated with insulin and glucose at various concentrations, and their content of malonyl-CoA was determined. In addition, the effect on malonyl-CoA of denervation and electrically-induced muscle contractions was assessed. The concentration of malonyl-CoA in the soleus, taken directly from a rat fed ad libitum, was 2.0 ± 0.2 nmol/g. In muscles incubated for 20 min in a medium devoid of added insulin and glucose, the concentration was decreased to 0.8 ± 0.2 nmol/g. When the medium contained 0.5, 7.5, or 30 mM glucose, malonyl-CoA concentrations were 1.3 ± 0.1, 1.8 ± 0.1, or 2.4 ± 0.2 nmol/g, respectively, in the absence of insulin and 1.7 ± 0.1, 4.6 ± 0.3 and 5.5 ± 0.6 nmol/g. in its presence (10 mU/ml). Compared with its level in a control muscle, the concentration of malonyl-CoA increased 3-fold in the soleus 6–8 h after denervation and remained 2-fold higher for ≥ 48 h. In contrast, muscle contractions induced by sciatic nerve stimulation, in vivo, acutely decreased the concentration of malonyl-CoA by 30–35%. The results indicate that insulin and glucose, and probably contractile activity, regulate the concentration of malonyl-CoA in muscle. They suggest that malonyl-CoA is a component of a fuel-sensing and signaling mechanism that responds to changes in the fuel milieu and possibly the energy expenditure of the muscle cell.

Proximally evoked soleus H reflexes in the evaluation of axonal neuropathy

It is sometimes difficult to differentiate physiologically distal axonopathy from proximal root or nerve disease. Standard soleus H reflexes evoked by distal tibial nerve stimulation at the popliteal fossa are often absent in both syndromes. In this study we distinguish the two by the presence or absence of soleus H reflexes evoked by proximal sciatic nerve stimulation at the gluteal fold. In 12 normal subjects maximum H reflex amplitudes evoked by distal tibial and proximal sciatic stimulation were essentially equal. In 12 patients with suspected distal polyneuropathy, proximal but not distal stimulation evoked H reflexes. By contrast, in 10 patients with lumbosacral root or proximal nerve disease, both proximal and distal stimulation failed to elicit H reflexes. In 2 patients with lower motor neuronopathy, low but comparable amplitude H reflexes were evoked at both sites. We conclude that the presence of a proximally evoked soleus H reflex may provide specific evidence of distal axonopathy when standard soleus H reflexes are absent.

CONTRACTILE FUNCTION OF REINNERVATED FAST AND SLOW TWITCH MUSCLES FOLLOWING DIFFERENT TYPES OF PERIPHERAL NERVE GRAFTS 380

Athletic trauma can result in peripheral nerves injury. In this study, the effects of storage on nerve graft were examined. In adult male Lewis rats(225-250 g), a 3-cm syngeneic interposition sciatic nerve graft was performed between the following donor and recipient groups: auto graft (n = 10); allo graft (n = 11); grafted after storage for 3 weeks (3Wk, n = 9); and grafted after freeze/thaw (FT; n = 9). Normal unoperated rats served as control (n = 8). At 16 weeks following sciatic nerve graft, forces from the slow twitch soleus (SOL) and the fast twitch plantaris (PLA) muscles were assessed by muscle stimulation and by sciatic nerve stimulation. SOL and PLA muscle masses from the operated groups decreased (p<0.05) to 50-55% of controls. Compared to controls, forces expressed in N were significantly (p<0.05) reduced in all groups. With two exceptions, forces normalized for muscle mass (N/g) were not different between groups. With nerve stimulation, SOL twitch force from the control group was greater (p<0.05) than (3.217 ± 0.22 N/g) those of the Allo graft group (1.253 ± 0.285 N/g), while PLA tetanic force was significantly lower in the FT group (13.928 ± 0.966 N/g) compared to controls (25.788 ± 1.353 N/g). This data show no consistent ability of one nerve graft to be more effective than another.

Estimation of shear and flow rates in pial arterioles during somatosensory stimulation.

We tested the hypothesis that a shear stress-dependent mechanism is involved in the dilation of pial arterioles during somatosensory stimulation. In alpha-chloralose-anesthetized rats implanted with cranial windows, we simultaneously measured the diameter and flow velocity of pial arterioles with video and dual-slit methods. Stimulation (0.2-0.3 V, 5 Hz, 0.5 ms pulses for 20 s) of the contralateral sciatic nerve evoked consistent dilator responses in pial arterioles (36 +/- 1 micron diam) without affecting blood pressure. The dilator responses consisted of an initial transient peak dilation of 30 +/- 3%, followed by a sustained dilation of 13 +/- 1% (n = 11). Mean velocity increased by 16.4 +/- 5.7% at 5 s after stimulus onset. Wall shear rate and volume flow were calculated from diameter and velocity data by assuming a parabolic flow profile. There was no significant change in wall shear rate, whereas flow rate increased significantly during sciatic nerve stimulation. The present findings suggest that a flow (shear stress)-mediated mechanism does not play an important role in the dilator response of pial arterioles to sciatic nerve stimulation.

Bilaterally enhanced dorsal horn postsynaptic currents in a rat model of peripheral mononeuropathy

Surface compound potentials were recorded from the surgically exposed lumbar spinal cord in anaesthetized rats which had had one sciatic nerve loosely ligatured 12–15 days previously, resulting in unilateral allodynia and hyperalgesia, as assessed behaviourally. These cord dorsum potentials were recorded in response to electrical stimulation of the ligatured and non-ligatured sciatic nerve, respectively, on both the ipsi- and contralateral side with respect to the stimulated nerve. Compared to potentials produced by stimulation of the non-ligatured sciatic nerve, electrical stimulation of large diameter fibres proximal to the ligatures resulted in a smaller afferent fibre input arriving at the spinal cord. However, larger net postsynaptic currents in the contralateral dorsal horn and a larger net post-synaptic current per unit of afferent fibre input were found in the ipsilateral and contralateral spinal cord. Such changes may result from structural changes or increased synaptic efficacy in the dorsal horn following peripheral nerve injury.

The Effects of an RNA Synthesis Inhibitor on the Survival and Regeneration of Rat Motoneurones Injured at Birth

This preliminary study aimed to test the proposal that neuronal death is triggered by expression of specific genes. In rat pups, the sciatic nerve was injured unilaterally on the first day after birth and actinomycin D, an RNA synthesis inhibitor, was administered 3 days later in a lower and higher dose to rat pups just prior to onset of motoneurone death induced by the lesion. Four weeks later, sciatic motoneurones from operated and contralateral pools were counted and their size measured. Significantly fewer motoneurones (16.7% ± 2.9 SD) survived when the animals were treated with a lower dose of the inhibitor compared to saline treated controls (36.6% ± 12.7 SD). Experiments recording tension generated in soleus muscle in response to sciatic nerve stimulation, at different ages following nerve crush, suggested that the treatment with the RNA synthesis inhibitor may have delayed regeneration of motor axons back to the muscle. However, survival of motoneurones after treatment with the higher dose did not differ significantly from controls (27.5% ± 1.3 SD. Nevertheless, the higher dose significantly reduced growth of motoneurones after 4 weeks. Therefore, the higher dose, although impeding normal development of motoneurones, is less neurotoxic than a lower dose. This suggests that a balancing of conflicting effects may have occurred. The neurodegenerative effects of delayed reinnervation induced by RNA synthesis inhibition may be balanced by some neuroprotective effects at a higher dose. More extensive studies are required to validate these pilot findings.

Functional changes of the peripheral nervous system with aging in the mouse

The influence of aging on peripheral nerve and target organ function was investigated in six groups of mice aged 2, 6, 9, 12, 18, and 24 months. Sudomotor, motor, and sensory functions mediated by the sciatic nerve were evaluated by silicone imprints, electrophysiological recordings and pinprick test from the distal hindpaw. Nerve conduction was also studied in the caudal nerves. The results showed that the number of sweat glands reactive to pilocarpine does not change significantly with aging, but the size of the sweat droplets is smaller in aged mice than in young mice. The amplitude of muscle and nerve action potentials evoked by stimulation of sciatic and caudal nerves decreased progressively from 2 to 24 months, while the latencies decreased from 2 to 6 months, remained unchanged until 12 months and increased thereafter. All the animals of the six groups studied showed positive, indistinguishable responses to pinprick. These results indicate that neurophysiological responses mediated by large diameter nerve fibers deteriorated with age, while those dependent of small fibers were preserved.

Potentiels évoqués somesthésiques: morphologie et relations interaréales SI-MI chez le singe ( Papio papio)

Primary somatosensory potentials (SEPs) were elicited by electrical stimulation of the medial sciatic (proprioceptive) or sural (cutaneous) nerves. They were detected by contacts on SI and MI dura on both cortical sides against a cephalic reference. SEPs were averaged (n = 20). Primary SI SEP consisted of positive, then negative, PI6/N30 waves. N30 was absent from MI records. Local electrocoagulation of the SI cortex on one side has entailed some reduction, but not suppression of together the homolateral MI and contralateral SI and MI SEP. The residual SEPs have increased in latencies by a few milliseconds. Additional coagulation of the MI area on the same side has resulted in loss of the SI and MI SEP on the opposite hemisphere when evoked by a stimulation ipsilateral to this intact cortex. Normal SEPs were elicited from the intact cortex by any of the used stimulation. No evoked signal could be evidence from the lesioned areas. It was concluded that negligible passive electrical diffusion from any SEP area was present onto any of the other SEP reception sites. From close comparison between the different records, we came to the following propositions: each of the SI and MI areas harbours a neural mass generator for SEPs elicited by contralateral nerve stimulation. SI and MI SEPs cannot be directly elicited by ipsilateral stimulus. SI and MI SEP ipsilateral to the nerve stimulation are due to some cortico-cortical trans-sagittal excitatory message arising from the contralateral SI/MI areas. Data stand for exteroceptive or proprioceptive stimulation as well. The absence of ipsilateral direct spino-cortical projection for SEP evidenced under barbiturate does also exist in the baboon after total recovery of surgery. A scheme is given which summarizes these active relationships between somesthetic areas.

Metocurine pharmacokinetics and pharmacodynamics in goats.

Non-depolarizing muscle relaxants can facilitate surgery and anaesthesia in numerous species. and volatile inhalational anaesthetics such as isoflurane potentiate their action. We studied the effect of isoflurane on the pharmacodynamics and pharmacokinetics of metocurine in six goats. Each was studied twice: once during barbiturate-opiate anaesthesia and once during isoflurane anaesthesia. The evoked response to sciatic nerve stimulation was measured using a force transducer attached to the hoof. Metocurine was infused until approximately 80-90% blockade. Plasma metocurine concentration was determined by high-performance liquid chromatography. Isoflurane increased the potency of metocurine significantly; IC50 (the concentration in the effect compartment at 50% paralysis) was 70 +/- 15 ng/mL during isoflurane anaesthesia and 129 +/- 42 ng/mL during barbiturate-opiate anaesthesia (P < 0.03). Volume of distribution (63 +/- 18 mL/kg), clearance (1.6 +/- 0.4 mL/min.kg) and elimination half-life (99 +/- 9 min) during barbiturate-opiate anaesthesia were not significantly different during isoflurane anaesthesia: 64 +/- 25 mL/kg, 1.5 +/- 0.7 mL/kg.min, 116 +/- 16 min respectively. We conclude that, relative to barbiturate-opiate anaesthesia, isoflurane potentiates metocurine in goats.

L-NNA suppresses cerebrovascular response and evoked potentials during somatosensory stimulation in rats.

We studied the local cerebrovascular response and somatosensory-evoked potentials (SEPs) to stimulation of the sciatic nerve during both short- (< 30 min) and long-term (90-150 min) exposure to topically applied NG-nitro-L-arginine (L-NNA). The pial circulation was visualized through a cranial window in alpha-chloralose-anesthetized rats. The diameter of pial arterioles (25-45 microns) and laser-Doppler flow (LDF) in the hindlimb sensory cortex were simultaneously measured during sciatic nerve stimulation. Short-term (< 30 min) treatment with L-NNA (1 mM) abolished the dilation of pial arterioles induced by acetylcholine, whereas the response to sciatic nerve stimulation was not affected. When applied for > 30 min, L-NNA induced severe vasomotion and attenuated the vascular responses to sciatic nerve stimulation. Long-term exposure to topically (1 mM) or systemically (10 mg/kg i.v.) applied L-NNA also attenuated cortical SEPs to sciatic nerve stimulation. Thus L-NNA-induced inhibition of vascular responses may be secondary to suppression of neuronal activity and an L-arginine metabolite, such as nitric oxide, may be involved in neurotransmission in the cerebral cortex during somatosensory activity.

Rat skeletal muscle metabolism in experimental heart failure: effects of physical training.

Skeletal muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on muscle metabolism after myocardial infarction was studied in a rat model. 31P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of muscle metabolism was achieved by training without any change in calf muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of skeletal muscle metabolism, implicating decreased physical activity in the aetiology of these changes.

A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation

Increases in the concentration of malonyl-CoA in skeletal muscle have been observed in the KKAy mouse, an obese rodent with high plasma insulin and glucose levels [Saha et al. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E95-E101, 1994]. To assess whether insulin and glucose directly regulate malonyl-CoA in muscle, soleus muscles from young rats were incubated with insulin and glucose at various concentrations, and their content of malonyl-CoA was determined. In addition, the effect on malonyl-CoA of denervation and electrically induced muscle contractions was assessed. The concentration of malonyl-CoA in the soleus, taken directly from a rat fed ad libitum, was 2.0 +/- 0.2 nmol/g. In muscles incubated for 20 min in a medium devoid of added insulin and glucose, the concentration was decreased to 0.8 +/- 0.2 nmol/g. When the medium contained 0.5, 7.5, or 30 mM glucose, malonyl-CoA levels were 1.3 +/- 0.1, 1.8 +/- 0.1, or 2.4 +/- 0.2 nmol/g, respectively, in the absence of insulin and 1.7 +/- 0.1, 4.6 +/- 0.3, or 5.5 +/- 0.6 nmol/g in its presence (10 mU/ml). Compared with its level in a control muscle, the concentration of malonyl-CoA was increased threefold in the soleus 6-8 h after denervation and remained twofold higher for > or = 48 h. In contrast, muscle contractions induced by sciatic nerve stimulation, in vivo, acutely decreased the concentration of malonyl-CoA by 30-35%. The results indicate that insulin and glucose, and probably contractile activity, regulate the concentration of malonyl-CoA in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Triiodothyronine-induced changes in proton efflux from rat skeletal muscle in vivo

Hyperthyroidism is associated with muscle weakness, abnormal aerobic metabolism and increased lactate production. Muscle cell acidification during exercise is reduced, suggesting abnormally increased proton efflux. Using 31P magnetic resonance spectroscopy to measure cell pH and phosphocreatine concentration, we quantified effective proton efflux from rat leg muscle in vivo following 10-Hz sciatic nerve stimulation in seven rats injected with triiodothyronine (T3) for 5 days and in 11 controls. Proton efflux during recovery was sigmoidally pH-dependent in both groups but the initial proton efflux rate did not differ (16 +/- 3 mmol.kg-1.min-1 in treated animals vs 15 +/- mmol.kg-1.min.-1 in controls), despite significantly smaller pH change from basal in treated animals (0.60 +/- 0.04 vs 0.78 +/- 0.03 in controls, p = 0.002). The pH dependence of proton efflux can be characterized by an apparent Km, defined as the pH below basal at which proton efflux rate falls to half its start-of-recovery value. This Km was smaller in the T3-treated group (0.44 +/- 0.04 vs 0.59 +/- 0.03 in controls, p = 0.02). This suggests an increased affinity for protons by cell membrane proton transport processes such as the sodium-proton antiporter and may explain some of the metabolic changes seen clinically in hyperthyroid skeletal muscle.