Gastric Electrical Stimulation for Obesity: The Need for a New Device Using Wider Pulses

Gastric electrical stimulation (GES) has been proposed as a therapeutic option for obesity. However, its clinical efficacy is not proven, and its mechanisms remain largely unknown. To compare the peripheral and central neural and behavioral effects in rats of GES with a pulse width currently used in clinical trials (GES‐A: 6 mA, 0.3 ms, 40 Hz, 2 s on, 3 s off) and GES with a wider pulse (GES‐B: same as GES‐A, except that the pulse width is 3 ms). Experiment 1: assessing gastric volume changes as a result of GES. Experiment 2: recording the extracellular potentials of a single neuron in the paraventricular nucleus (PVN) with GES. Experiment 3: determining the effects of GES on oxytocin‐immunoreactive (OT‐IR) neuron expression in the hypothalamus. Experiment 4: determining the effects of GES on food intake and body weight. GES‐B, but not GES‐A, significantly increased gastric volume. GES‐B activated a higher percentage of gastric distention‐responsive neurons in the PVN (93% vs. 81%, P = 0.021) and elicited more intensive neuronal responses than GES‐A. The number of OT‐IR neurons was significantly increased in the PVN and supraoptic nucleus with both methods of GES compared with control groups. The increase in OT‐IR neurons in the PVN was higher with GES‐B than with GES‐A. A 1‐week GES treatment significantly reduced daily food intake and body weight. GES‐B was more potent than GES‐A in producing weight loss (P < 0.001). The effects of GES depend on the stimulation pulse width. GES with a wider pulse is more effective both peripherally and centrally and more potent in reducing body weight in rats.     

胃多导电刺激及胃液体排空犬动物模型的建立

目的建立胃浆膜多导联电刺激和胃排空动物模型。方法在12条英国比格犬的胃大弯浆膜层包埋四对心内起搏电极,距幽门40cm空肠近端行一造瘘口。结果①造瘘管收集食糜的方法简单易行,通过其排空量,能了解不同的电刺激和不同的电刺激参数对胃动力的作用。②胃浆膜多导联电极记录的胃体、胃窦慢波电信号清晰、稳定,能准确地记录不同时间和不同实验的胃慢波变化。③单导联和多导长脉冲电刺激均能控制胃慢波。结论胃浆膜多导联电极是研究胃电生理、胃电起搏及胃电起搏对胃排空的影响较理想的方法。英国比格犬是此模型的理想材料。     

Effect of transcutaneous transcerebral electrostimulation as electroanesthesia on the beta-endorphin content of the cerebrospinal fluid and blood plasma

The beta-endorphin content was measured in the cerebrospinal fluid (CSF) and blood plasma of patients before and after 30 minutes of transcutaneous transcerebral electric stimulation in the electric anesthesia mode. The output current was biphasic and rectangular. It was composed of high-frequency pulse trains (peak-to-peak intensity 250-300 mA, frequency 167 kHz) modulated by low frequency (77 Hz). Electrical stimulation resulted in an appreciable increase in the beta-endorphin content in the CSF and blood plasma of patients. The data obtained attest to the intensification of the neuromodulator release to the CSF and blood plasma and to the involvement of the endorphinergic brain systems in the realization of the analgetic effect of transcutaneous transcerebral electric stimulation.     

Gastric electrical stimulation inhibits postprandial antral tone partially via nitrergic pathway in conscious dogs

Gastric electrical stimulation (GES) has recently been explored as a therapeutic option for gastrointestinal motility disorders or obesity. The mechanism behind it is not fully elucidated. The aims of this study were to assess the effects of GES with different parameters on antral tone and to explore the involvement of the nitrergic pathway. Eight dogs equipped with a gastric cannula and one pair of serosal electrodes in the greater curvature 4 cm above the pylorus were studied on separate days. The study was composed of seven randomized sessions in the fed state [control, GES with different parameters, and GES plus neuronal nitric oxide synthase (nNOS) inhibitor]. Each session included three consecutive 30-min periods (baseline, GES, and recovery). GES was performed with long pulses or pulse trains. The antral volume was measured using an intragastric balloon connected with a barostat device. Behaviors of the dogs during each stimulation period were also noted. We found that 1) postprandial antral tone was reduced with GES with all tested parameter settings, reflected as a significant and substantial increase in antral volume ranging from 179 to 309%; 2) the inhibitory effect of GES on antral tone was partially blocked (decreased by 39.5%) with an nNOS inhibitor; and 3) mild symptoms were induced with GES and found to be correlated with the GES-induced increase in antral volume. We conclude that retrograde GES with long pulses or pulse trains inhibits antral tone, and this inhibitory effect is partially mediated via the nitrergic pathway. These results suggest that retrograde GES may have a therapeutic potential for obesity.     

Effects of gastric electric stimulation on gastric distention responsive neurons and expressions of CCK in rodent hippocampus

Objective: Gastric electrical stimulation (GES) has been introduced for treating obesity. The hippocampus is known to be involved in the regulation of gastrointestinal motility. Changes in hypathalumus cholecystokinin (CCK) have been observed in genetically obese rodents. This experiment was to study the effect of GES on the activities of neurons and the expression of CCK in the hippocampus. Methods and Procedures: We investigated the effect of GES (GES‐I: pulse train of standard parameters; GES‐2: reduced train‐on time; GES‐3: increased pulse width; GES‐4: reduced pulse frequency) on neurons responsive to gastric distention (GD) by recording extracellular potentials of single neurons and observing the expression of CCK in the rodent hippocampus by immunohistochemistry staining, radioimmunoassay, and real‐time PCR. Results: 92.1% of neurons in the CA2‐3 region responded to GD, 53.2% of which showed excitation (GD‐E), and 46.8% showed inhibition (GD‐I). 64.8% GD‐responsive neurons were excited by GES. The response was associated with stimulation strength, pulse width, and frequency; 70.6, 57.1, 94.4, and 66.7% of GD‐E and 72.7, 57.1, 86.4, and 50% of GD‐I neurons showed excitatory responses to GES‐I, ?2, ?3, and ?4, respectively. CCK immunoreactive positive neurons (P < 0.001), the content of CCK‐like materials (P < 0.05) and the amount of CCK mRNA were significantly increased after GES (P < 0.05). Discussion: These findings suggest the central, neuronal, and hormonal mechanisms of GES. GES may excite the activity of GD‐sensitive neurons and increase the expression of CCK in the hippocampus. These excitatory effects of GES seem to be related to the parameters of stimulation.     

Noninvasive assessment of the effects of glucagon on the gastric slow wave

Hyperglycemic effects on the gastric slow wave are not well understood, and no studies have examined the effects that hyperglycemia has on gastric slow wave magnetic fields. We recorded multichannel magnetogastrograms (MGGs) before and after intravenous administration of glucagon and subsequent modest hyperglycemia in 20 normal volunteers. Normal slow waves were evident in baseline MGG recordings from all 20 subjects, but within 15 min after glucagon had been given, we noted significant effects on MGG signals. In addition to an overall decrease in the slow wave frequency from 2.9 +/- 0.5 cycles per min (cpm) to 2.2 +/- 0.1 cpm (P < 0.05), we observed significant changes in the number and range of spectral peaks recorded. Furthermore, the propagation velocity determined from surface current density maps computed from the multichannel MGG decreased significantly (7.1 +/- 0.8 mm/s to 5.0 +/- 0.3 mm/s, P < 0.05). This is the first study of biomagnetic effects of hyperglycemia in normal subjects. Our results suggest that the analysis of the MGG provides parameter quantification for gastric electrical activity specific to and characteristic of slow wave abnormalities associated with increased serum glucose by injection of glucagon.     

Single motor unit and fiber action potentials during fatigue

Muscle fatigue is defined as a loss of tension development during constant stimulation. Although the relationship is not well documented, muscle fatigue has been inferred from electromyogram (EMG) signals. The purpose of this study was to determine the relationship between the amplitude and duration of single motor unit action potentials (MUAPs) and the loss of tension development (fatigue) in the medial gastrocnemius muscles of cats. Single motor units were fatigued by continuous stimulation at 10 or 80 Hz or with trains of 40-Hz stimuli. When motor units were stimulated at 10 Hz and with trains at 40 Hz (low frequency), tension declined and remained depressed during recovery. The changes in the MUAP correlated poorly with changes in tension. During and after stimulation at 80 Hz (high frequency), changes in the amplitude and duration of MUAPs correlated highly with changes in tension development. Since the EMG signal is dependent on a summation and cancellation of individual MUAPs, the EMG provides a reasonable estimate of high-frequency fatigue but an unreliable measure of low-frequency fatigue.     

Neural regulation of slow-wave frequency in the murine gastric antrum

Gastric peristaltic contractions are driven by electrical slow waves modulated by neural and humoral inputs. Excitatory neural input comes primarily from cholinergic motor neurons, but ACh causes depolarization and chronotropic effects that might disrupt the normal proximal-to-distal spread of gastric slow waves. We used intracellular electrical recording techniques to study cholinergic responses in stomach tissues from wild-type and W/W(V) mice. Electrical field stimulation (5 Hz) enhanced slow-wave frequency. These effects were abolished by atropine and the muscarinic M(3)-receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide. ACh released from nerves did not depolarize antral muscles. At higher rates of stimulation (10 Hz), chronotropic effects were mediated by ACh and a noncholinergic transmitter and blocked by muscarinic antagonists and neurokinin (NK(1) and NK(2))-receptor antagonists. Neostigmine enhanced slow-wave frequency, suggesting that the frequency of antral pacemakers is kept low by efficient metabolism of ACh. Neostigmine had no effect on slow-wave frequency in muscles of W/W(v) mice, which lack intramuscular interstitial cells of Cajal (ICC-IM). These muscles also showed no significant chronotropic response to 5-Hz electrical field stimulation or the cholinergic agonist carbachol. The data suggest that the chronotropic effects of cholinergic nerve stimulation occur via ICC-IM in the murine stomach. The capacity of gastric muscles to metabolize ACh released from enteric motor neurons contributes to the maintenance of the proximal-to-distal slow-wave frequency gradient in the murine stomach. ICC-IM play a critical role in neural regulation of gastric motility, and ICC-IM become the dominant pacemaker cells during sustained cholinergic drive.     

Therapeutic potential of synchronized gastric electrical stimulation for gastroparesis: enhanced gastric motility in dogs

The aim of this study was to determine the effects and mechanism of synchronized gastric electrical stimulation (SGES) on gastric contractions and gastric emptying. The first experiment was designed to study the effects of SGES on antral contractions in four randomized sessions. Sessions 1 (control) and 2 (atropine) were performed in the fasting state, composed of three 30-min periods (baseline, stimulation, and recovery). Sessions 3 (control) and 4 (SGES performed during 2nd 20-min period) were performed in the fed state, consisting of two 20-min periods; glucagon was injected after the first 20-min recording. The second experiment was designed to study the effect of SGES on gastric emptying and consisted of two sessions (control and SGES). SGES was delivered with train duration of 0.5-0.8s, pulse frequency of 40 Hz, width of 2 ms, and amplitude of 4 mA. We found that 1) SGES induced gastric antral contractions in the fasting state. The motility index was 1.3 +/- 0.5 at baseline and 6.1 +/- 0.7 (P = 0.001) during SGES. This excitatory effect was completely blocked by atropine. 2) SGES enhanced postprandial antral contractions impaired by glucagon. 3) SGES significantly accelerated glucagon-induced delayed gastric emptying. Gastric emptying was 25.5 +/- 11.3% without SGES and 38.3 +/- 10.7% with SGES (P = 0.006 vs. control). This novel method of SGES induces gastric antral contractions in the fasting state, enhances glucagon-induced antral hypomotility in the fed state, and accelerates glucagon-induced delayed gastric emptying. The effect of SGES on antral contractions is mediated via the cholinergic pathway.     

Catchlike property in human adductor pollicis muscle

The "catchlike" property is defined as the dramatic force increase in skeletal muscles when a single pulse is added at the onset of a sub-tetanic low-frequency stimulation train. This property has been observed in single motor units, whole animal and human muscles. It is an inherent property of muscle fibres and is not related to an increase in motor unit recruitment. Despite an abundance of observations, its origin remains unclear. The aim of this study was to induce the catchlike property in human adductor pollicis and identify its possible origin. Thumb adduction forces were measured using ulnar nerve electrical stimulation at 10Hz for reference trains (RTs) with one extra pulse 8ms after the first stimulation pulse for the experimental trains (ETs). Tests were performed at two muscle length and three stimulation levels and muscle stiffness and potentiation were quantified for all test conditions. The ETs showed higher forces and greater rates of force increase than the RTs. In addition, force increase was more pronounced at short compared to long muscle length, but no differences were found in force increase for the three stimulation levels. Furthermore, potentiation and stiffness were similar across all experimental conditions. Together, these results suggest that the increase in force associated with the catchlike property is neither caused by an increased proportion of attached cross-bridges nor potentiation of the muscle, but appears to be muscle length dependent and present in both slow and fast motor units.     

大鼠海马神经元对于高频脉冲刺激的暂态响应

闭环刺激是深部脑刺激(deep brain stimulation,DBS)的重要发展方向之一,有望用于治疗多种脑神经系统疾病.与常规开环的长时间持续刺激不同,闭环刺激通常采用短促的高频脉冲序列.而神经元对于高频刺激的响应存在暂态过程,在初期的短时间内会发生很大变化,从而影响闭环刺激的作用.为了研究这种暂态过程,在大鼠...     

Mouse Postganglionic Sympathetic Neurons

Basic properties of noradrenaline release were studied in primary cultures of thoracolumbar postganglionic sympathetic neurons taken from 1-3-day-old NMRI mice. After 7 days in vitro, the cultures were preincubated with [3H]noradrenaline and then superfused and stimulated electrically. Conventional trains of pulses (for example, 36 pulses at 3 Hz) as well as single pulses and brief high-frequency trains (for example, four pulses at 100 Hz) elicited a well-measurable overflow of tritium, which was abolished by 0.3 microM tetrodotoxin or omission of Ca2+, but not changed by 1 microM rauwolscine. In trains of one, two, four, six, eight, or 10 pulses at 3 Hz, the evoked overflow of tritium remained constant from pulse to pulse at 1.3 mM Ca2+, but declined slightly at 2.5 mM Ca2+. Tetraethylammonium at 10 mM selectively increased the overflow elicited by small pulse numbers and especially by a single pulse. In trains of 10 pulses delivered at 0.3, 1, 3, 10, 30, or 100 Hz, the evoked overflow of tritium increased from 0.3 to 30 Hz and then declined at 100 Hz. This relationship was particularly pronounced at low Ca2+ concentrations (for example, 0.3 mM). Tetraethylammonium at 10 mM selectively increased the overflow elicited by low frequencies of stimulation. It is concluded that primary cultures of mouse postganglionic sympathetic neurons can be used to investigate release of [3H]noradrenaline. The release is well measurable, even upon a single electrical pulse. It agrees with release in intact sympathetically innervated tissues in a number of fundamental properties, including the pulse number and frequency dependence. The preparation may be of special interest in conjunction with genetic manipulations in the donor animals.     

Preferential Release of ATP and Its Extracellular Catabolism as a Source of Adenosine upon High- but Not Low-Frequency Stimulation of Rat Hippocampal Slices

Abstract: The release of adenosine and ATP evoked by electrical field stimulation in rat hippocampal slices was investigated with the following two patterns of stimulation: (1) a brief, high-frequency burst stimulation (trains of stimuli at 100 Hz for 50 ms applied every 2 s for 1 min), to mimic a long-term potentiation (LTP) stimulation paradigm, and (2) a more prolonged (3 min) and low-frequency (5 Hz) train stimulation, to mimic a long-term depression (LTD) stimulation paradigm. The release of ATP was greater at a brief, high-frequency burst stimulation, whereas the release of [³H]adenosine was slightly greater at a more prolonged and low-frequency stimulation. To investigate the source of extracellular adenosine, the following two pharmacological tools were used; α,β-methylene ADP (AOPCP), an inhibitor of ecto-5′-nucleotidase, to assess the contribution of the catabolism of released adenine nucleotides as a source of extracellular adenosine, and S-(4-nitrobenzyl)-6-thioinosine (NBTI), an inhibitor of adenosine transporters, to assess the contribution of the release of adenosine, as such, as a source of extracellular adenosine. At low-frequency stimulation, NBTI inhibited by nearly 50% the evoked outflow of [³H]adenosine, whereas AOPCP inhibited [³H]adenosine outflow only marginally. In contrast, at high-frequency stimulation, AOPCP inhibited by 30% the evoked release of [³H]adenosine, whereas NBTI produced a 40% inhibition of [³H]adenosine outflow. At both frequencies, the kinetics of evoked [³H]adenosine outflow was affected in different manners by AOPCP and NBTI; NBTI mainly depressed the rate of evoked [³H]adenosine outflow, whereas AOPCP mainly inhibited the later phase of evoked [³H]adenosine accumulation. These results show that there is a simultaneous, but quantitatively different, release of ATP and adenosine from rat hippocampal slices stimulated at frequencies that can induce plasticity phenomena such as LTP (100 Hz) or LTD (5 Hz). The source of extracellular adenosine is also different according to the frequency of stimulation; i.e., at a brief, high-frequency stimulation there is a greater contribution of released adenine nucleotides for the formation of extracellular adenosine than at a low frequency with a more prolonged stimulation.     

Ghrelin, appetite and gastric electrical stimulation

Ghrelin is a peptide hormone produced mainly by the stomach and has widespread physiological functions including increase in appetite. The stimulation of the ghrelin system represents a potential therapeutic approach in various disorders characterized by deficient ghrelin signaling or by low appetite. This stimulation may be achieved via pharmacological targeting of the ghrelin receptor with synthetic ghrelin or ghrelin mimetics or via increased endogenous ghrelin production. Recently, it was demonstrated that gastric electrical stimulation (GES) with Enterra parameters results in increased ghrelin production in rats. Furthermore, recent data revealed putative role of ghrelin-reactive immunoglobulins in the modulation of the ghrelin signaling which can be also stimulated by GES. Here, we review the links between GES and ghrelin in existing GES experimental and clinical applications for treatment of gastroparesis, functional dyspepsia or obesity and discuss if GES can be proposed as a non-pharmacological approach to improve ghrelin secretion in several pathological conditions characterized by low appetite, such as anorexia nervosa or anorexia-cachexia syndrome.     

Gastric Electrical‐Stimulation Effects on Canine Gastric Emptying,Food Intake,and Body Weight

Objective: It has been reported that electrical stimulation at the distal stomach can disrupt intrinsic gastric electrical activity and delay gastric emptying. Gastric dysrhythmia and impaired gastric emptying are associated with upper gastrointestinal symptoms and weight loss. The purpose of this study was to evaluate the effect of low‐frequency/long‐pulse gastric electrical stimulation (GES), at proximal and distal stomach, on canine gastric emptying, food intake, and body weight. Research Methods and Procedures: Eight dogs were surgically implanted with four pairs of electrodes along the greater curvature and a gastric tube at the dependent part of the stomach. Liquid gastric emptying at baseline, during proximal and distal GES at 6 cycles per minute, was assessed first by a dye dilution technique. Proximal and distal GES were then randomly delivered during feeding for 10 consecutive days, and food intake and body weight were recorded daily. Results: There was no significant difference in gastric emptying parameters among the various sessions. The mean daily food consumption was significantly reduced during both sessions of GES, resulting in significant immediate weight loss. Percentage weight loss was comparable between both sessions of GES. Discussion: Short‐term GES significantly reduced canine food intake and weight. This effect may not be related to changes in gastric emptying. GES may have a potential role in the treatment of obesity.     

Fatiguing contractions of tongue protrudor and retractor muscles: influence of systemic hypoxia.

The influence of systemic hypoxia on the endurance performance of tongue protrudor and retractor muscles was examined in anesthetized, ventilated rats. Tongue protrudor (genioglossus) or retractor (hyoglossus and styloglossus) muscles were activated via medial or lateral XII nerve branch stimulation (0.1-ms pulse; 40 Hz; 330-ms trains; 1 train/s). Maximal evoked potentials (M waves) of genioglossus and hyoglossus were monitored with electromyography. Fatigue tests were performed under normoxic and hypoxic (arterial PO(2) = 50 +/- 1 Torr) conditions in separate animals. The fatigue index (FI; %initial force) after 5 min of normoxic stimulation was 85 +/- 6 and 79 +/- 7% for tongue protrudor and retractor muscles, respectively; these values were significantly lower during hypoxia (protrudor FI = 52 +/- 10, retractor FI = 18 +/- 6%; P < 0.05). Protrudor and retractor muscle M-wave amplitude declined over the course of the hypoxic fatigue test but did not change during normoxia (P < 0.05). We conclude that hypoxia attenuates tongue protrudor and retractor muscle endurance performance; potential mechanisms include neuromuscular transmission failure and/or diminished sarcolemmal excitability.     

Functional vagal input to gastric myenteric plexus as assessed by vagal stimulation-induced Fos expression

Immunohistochemical detection of c-Fos expression was used to identify gastric myenteric plexus neurons that receive excitatory input from vagal efferent neurons activated by electrical stimulation of the cervical vagi in anesthetized rats. Vagal stimulation-induced Fos expression increased with higher pulse frequency, so that with 16 Hz (rectangular pulses of 1 mA/0.5 ms for 30 min) approximately 30% and with 48 Hz 90% of all neurons near the lesser curvature were Fos positive. In sham-stimulated rats there was no Fos expression. The percentage of Fos-activated neurons was only slightly smaller (85% with 48 Hz) near the greater curvature. Prior atropine administration (1 mg/kg ip) had little effect on vagal stimulation-induced Fos expression, and in unilaterally stimulated rats there was no Fos expression on the contralateral (noninnervated) side of the stomach, ruling out mediation by gastric motility or secretory responses. However, polysynaptic recruitment of third- and higher-order neurons cannot be ruled out completely. These results support the idea that, at least in the stomach, functional excitatory innervation of myenteric plexus neurons by the efferent vagus is profuse and widespread, refuting the notion of only a few vagal "command neurons."     

Differential Release of Endogenous 5-Hydroxytryptamine, Substance P., and Neurokinin A from Rat Ventral Spinal Cord in Response to Electrical Stimulation

Abstract: The release of endogenous 5-hydroxytryptamine (5-HT), substance P (SP), and neurokinin A (NKA) from superfused tissue slices of rat ventral lumbar spinal cord, where SP and NKA coexist with 5-HT in terminals of descending bulbospinal neurons, was investigated. Electrical field stimulation was performed using square-wave pulses of 2-ms duration and 30 mA stimulus intensity. The following four different patterns of stimulation were used: 2 Hz continuous, 20 Hz continuous, 20 Hz intermittent, and 50 Hz intermittent. 5-HT was measured in the slice superfusates by HPLC with electrochemical detection. SP and NKA were measured by radioimmunoassay. The release of 5-HT was significantly enhanced using all stimulation paradigms and the evoked release of 5-HT per pulse was independent of the stimulation frequency. The release was found to be calcium dependent and there was no increase in the efflux of 5-hydroxyindoleacetic acid in response to stimulation. At 2 Hz (continuous), no significant increase in the release of SP was observed. Stimulation at higher frequencies yielded a significant increase in the release of SP per pulse. At 20 Hz, the release was increased by 73% (continuous) and 74% (intermittent), and at 50 Hz (intermittent) by 175% of basal efflux. The evoked release of NKA was also frequency dependent. At 2 Hz (continuous), no significant increase in the release of NKA was observed. At 20 Hz (intermittent), the evoked release per pulse was increased by 33% and at 50 Hz (intermittent) by 53% compared with the basal efflux of NKA. The results suggest that coexisting neurotransmitters/neuromodulators in the spinal cord may be released in different proportions depending on the stimulation frequency and that only 5-HT is released when the nerve terminal is activated by low-frequency stimulation.     

A fast-twitch oxidative-glycolytic muscle with a robust inward calcium current

This report describes the histochemical and physiological properties of a rat skeletal muscle with a robust activity-dependent slow inward Ca2+ current. The muscle, the flexor digitorum brevis (FDB), is a small plantar flexor from the hindfoot. It is a homogeneous muscle consisting of approximately 90% fast-twitch oxidative-glycolytic (type IIA) fibers. Stimulation of the FDB with repetitive stimulus trains (30 or 50 Hz for 330 ms, 1 train/s for 2-5 min) produced a slow increase in the base-line or resting tension of the muscle between trains. This progressive increase in resting tension appears to be due to the activation of voltage-dependent slow Ca2+ channels, since it could be eliminated (i) by stimulating the muscle in a medium containing 2 mM EGTA and without Ca2+, and (ii) by the addition of either Co2+ or verapamil. The presence of a slow current may be associated with an increase in K+ efflux as stimulation continues, and with a prolongation of relaxation time. We also propose that the slow Ca2+ current may contribute to the allosteric activation of phosphorylase kinase during muscle activity. The FDB provides an excellent preparation to investigate the regulation of muscle metabolism by intra- and extra-cellular Ca2+ during exercise.     

Afferent mechanisms underlying stimulation modality-related modulation of acupuncture-related cardiovascular responses.

Despite the use of acupuncture to treat a number of heart diseases, little is known about the mechanisms that underlie its actions. Therefore, we examined the influence of acupuncture on sympathoexcitatory cardiovascular responses to gastric distension in anesthetized Sprague-Dawley rats. Thirty minutes of low-current, low-frequency, (0.3-0.5 mA, 2 Hz) electroacupuncture (EA), at P 5-6, S 36-37, and H 6-7 overlying the median, deep peroneal, and ulnar nerves significantly decreased reflex pressor responses by 40, 39, and 44%, respectively. In contrast, sham acupuncture involving needle insertion without stimulation at P 5-6 or 30 min of EA at LI 6-7 acupoints overlying the superficial radial nerve did not attenuate the reflex. Similarly, EA at P 5-6 using 40- or 100-Hz stimulation frequencies did not inhibit the reflex. Compared with EA at P 5-6, EA at two sets of acupoints, including P 5-6 and S 36-37, did not lead to larger inhibition of the reflex. Two minutes of manual acupuncture (MA; 2 Hz) at P 5-6 every 10 min for 30 min inhibited the reflex cardiovascular pressor response by 33%, a value not significantly different from 2-Hz EA at P 5-6. Single-unit afferent activity was not different between electrical stimulation (ES) and manual stimulation. However, 2-Hz ES activated more somatic afferents than 10- or 20-Hz ES. These data suggest that, although the location of acupoint stimulation and the frequency of stimulation determine the extent of influence of EA, there is little difference between low-frequency EA and MA at P 5-6. Furthermore, simultaneous stimulation using two acupoints that independently exert strong effects did not lead to an additive or a facilitative interaction. The similarity of the responses to EA and MA and the lack of cardiovascular response to high-frequency EA appear to be largely a function of somatic afferent responses.