Intermittent Electrical Stimulation Research Articles

Continuous and intermittent electrical stimulation of the aortic depressor nerve in conscious rats: time course of the hemodynamic responses

We investigated the time course of the hemodynamic responses to continuous (CONT) or intermittent (ON/OFF) electrical stimulation of the aortic depressor nerve (ADN) in conscious rats. Rats were implanted with electrodes around the ADN and a catheter into the femoral artery. On the next day the baseline systolic (SAP), diastolic (DAP), mean arterial pressure (MAP) and heart rate (HR) were recorded during 30 minutes and the rats were randomly assigned to CONT (0.5 mA; 0.25 ms; 30 Hz) or ON/OFF (5s ON/3s OFF; 0.5 mA; 0.25 ms; 30 Hz;) stimulation during 60 min. Changes were greater under CONT as compared to ON/OFF stimulation (SAP: −21 ± 4 vs −10 ± 2 %; DAP: −23 ± 4 vs −14 ± 3 %; MAP: −22 ± 4 vs −12 ± 3 %). In addition, under CONT stimulation the HR was reduced within the first 5 min. The hypotensive and bradycardic responses were maintained over the entire period of stimulation in the ON/OFF protocol. Nevertheless, as compared to the first 5 min, CONT stimulation showed a rapid transitory increase in DAP (72 ± 3 vs 64 ± 3 mmHg) and MAP (87 ± 3 vs 78 ± 4 mmHg). In conclusion, CONT stimulation of the ADN elicits greater hemodynamic responses as compared to the ON/OFF protocol. This finding indicates that the CONT stimulation is more effective to reduce the arterial pressure during long period of electric baroreflex activation.Financial support: FAPESP, CNPq and CAPES.

Vagal nerve stimulator: Evolving trends

Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future.

Prevention of deep tissue injury through muscle contractions induced by intermittent electrical stimulation after spinal cord injury in pigs

Deep tissue injury (DTI) is a severe medical complication that commonly affects those with spinal cord injury. It is caused by prolonged external loading of the muscles, entrapping them between a bony prominence and the support surface. The entrapment causes excessive mechanical deformation and increases in interstitial pressure, leading to muscle breakdown deep around the bony prominences. We proposed the use of intermittent electrical stimulation (IES) as a novel prophylactic method for the prevention of DTI. In this study, we assessed the long-term effectiveness of this technique in pigs that had received a partial spinal cord injury that paralyzed one hindlimb. The pigs recovered for 2 wk postsurgery, and subsequently, their paralyzed limbs were loaded to 25% of their body weights 4 h/day for 4 consecutive days each week for 1 mo. One group of pigs (n = 3) received IES during the loading, whereas another group (n = 3) did not. DTI was quantified using magnetic resonance imaging (MRI) and postmortem histology. In the group that did not receive IES, MRI assessments revealed signs of tissue damage in 48% of the volume of the loaded muscle. In the group that did receive IES, only 8% of the loaded muscle volume showed signs of tissue damage. Similar findings were found through postmortem histology. This study demonstrates, for the first time, that IES may be an effective technique for preventing the formation of DTI in loaded muscles after spinal cord injury.

Food Intake and Body Weight Responses to Intermittent vs. Continuous Gastric Electrical Stimulation in Diet-Induced Obese Rats

Gastric electrical stimulation (GES) has recently been introduced as a potential therapy for the treatment of obesity. The main challenge for the new generation of devices is to achieve desired clinical outcomes at a suitably low level of energy consumption. The aim of this study is to compare the effectiveness of GES with continuous and intermittent duty cycles in reducing food intake and body weight in diet-induced obesity-prone rats. In macro duty cycle experiment, 40 rats were divided into groups to receive a sham GES, continuous GES, or intermittent GES (15 min On-45 min Off or 15 min On-15 min Off) for 28 days. In micro duty cycle experiment, 18 rats received cross-over treatment of continuous stimulation, 60 % time cycle or 40 % time cycle. Food intake, body weight, gastric emptying and ghrelin level were measured to evaluate the effect of different GES. GES with macro duty cycle intensity-dependently reduced mean daily food intake increase by 18.6, 10.2 and -6.0 % compared to 42.7 % with sham GES and body weight gain by 6.1 %, 3.4 and -0.8 % compared to 5 % with sham GES. Daily food intake decreased with increasing micro duty cycle intensity, averaging 16.5, 15.6 and 13.7 g/day under 40 % cycle, 60 % cycle and continuous stimulation respectively. Gastric emptying was intensity-dependently delayed by GES. GES has no effect in modulating plasma ghrelin level. GES energy-dependently reduces food intake, body weight and gastric emptying. Peripheral modulation of plasma ghrelin level is not related to the GES effects.

Electrical Stimulation to Conductive Scaffold Promotes Axonal Regeneration and Remyelination in a Rat Model of Large Nerve Defect

BackgroundElectrical stimulation (ES) has been shown to promote nerve regeneration when it was applied to the proximal nerve stump. However, the possible beneficial effect of establishing a local electrical environment between a large nerve defect on nerve regeneration has not been reported in previous studies. The present study attempted to establish a local electrical environment between a large nerve defect, and examined its effect on nerve regeneration and functional recovery.Methodology/FindingsIn the present study, a conductive scaffold was constructed and used to bridge a 15 mm sciatic nerve defect in rats, and intermittent ES (3 V, 20 Hz) was applied to the conductive scaffold to establish an electrical environment at the site of nerve defect. Nerve regeneration and functional recovery were examined after nerve injury repair and ES. We found that axonal regeneration and remyelination of the regenerated axons were significantly enhanced by ES which was applied to conductive scaffold. In addition, both motor and sensory functional recovery was significantly improved and muscle atrophy was partially reversed by ES localized at the conductive scaffold. Further investigations showed that the expression of S-100, BDNF (brain-derived neurotrophic factor), P0 and Par-3 was significantly up-regulated by ES at the conductive scaffold.Conclusions/SignificanceEstablishing an electrical environment with ES localized at the conductive scaffold is capable of accelerating nerve regeneration and promoting functional recovery in a 15 mm nerve defect in rats. The findings provide new directions for exploring regenerative approaches to achieve better functional recovery in the treatment of large nerve defect.

Distribution of Internal Strains Around Bony Prominences in Pigs

Deep tissue injury (DTI) is a type of pressure ulcer in which tissue breakdown initiates at the bone-muscle interface under intact skin. Excessive deformation in the soft tissue, particularly around bony prominences, is believed to be one of the causes leading to the development of DTI. The main goal of this study was to measure the magnitude and distribution of strains within muscles surrounding the ischial tuberosities, induced by levels of external loading that encompass the range of loading experienced by the soft tissue in seated individuals. The experiments were conducted in adult pigs with intact spinal cords (n = 5) and pigs with partial spinal cord injury (SCI) (n = 2), one of which also had a DTI. A secondary goal was to obtain a preliminary assessment regarding the capacity of intermittent electrical stimulation (IES), an intervention for preventing the formation of DTI, to counteract the muscle compression caused by external loading. In intact animals, muscles subjected to external loads equivalent to 25% of body weight experienced maximal principal strains, minimal principal strains, and shear strains of 0.68, -0.3, and 0.4, respectively. These magnitudes increased by 91.9, 17.6, and 87.5%, respectively, when external loading increased to 50% body weight. Minimal to no further increases in strain magnitudes were seen with the 75% body weight loading level. In one animal with SCI and no DTI, strain magnitudes were on average 9.7% higher than those in the intact animals at the corresponding loading levels. The presence of a DTI in another animal with SCI reduced strain magnitudes by 28% compared to intact animals. The regions in the muscle that underwent the largest deformations were those between the ischial tuberosity and the external surface, and up to 2 cm ventral to the ischial tuberosity (furthest measured). Muscle contractions produced by IES increased the thickness of the tissue between the ischial tuberosities and skin during the period of stimulation by 10-20% for loading levels up to 75% of body weight in both intact and spinal cord injured pigs. This study provides the first measurements of strain around the ischial tuberosities in an animal model that resembles humans.

Repetitive sensory stimulation in stroke rehabilitation - perspectives and potential

Sensorimotor impairment resulting from stroke can have extensive physical, psychological, economic, and social implications despite available neurorehabilitative treatments. Intact somatosensory input is not only crucial for tactile perception but also for sensorimotor performance. Loss of sensory abilities further complicates the individual’s ability for functional tasks in spite of possible recovery of motor functions. Generally, rehabilitation following stroke based on neuroplasticity mechanisms utilizes task specific training and massed practice to drive reorganization and improve sensorimotor function. However, since many patients suffer from restricted mobility, development of additional and alternative approaches that could supplement, enhance, or even replace conventional training procedures would be advantageous. Therefore, in the past, many attempts have been made to implement additional rehabilitative approaches that make use of repetitive sensory stimulation. We use high-frequency intermittent electrical stimulation on all fingers of the affected hand. The rational is to induce plasticity processes within and around those brain areas that became dsyfunctional. A major advantage of repetitive stimulation is its passive nature, which does not require active participation or attention. Therefore, it can be applied in parallel to other occupations, making it easier to implement and more acceptable to the individual. Our data from subacute and long-term chronic patients showed that repetitive stimulation induced substantial improvement of tactile and sensorimotor performance long lasting when applied over weeks. Furthermore, positive effects in long-term chronic patients might emerge only after months of intervention. Accordingly, this effectiveness together with the advantage of usage under everyday conditions by laypeople at their homes, make repetitive sensory stimulation-based principles prime candidates for interventions in impaired populations.

Distribution of Internal Pressure around Bony Prominences: Implications to Deep Tissue Injury and Effectiveness of Intermittent Electrical Stimulation

The overall goal of this project is to develop interventions for the prevention of deep tissue injury (DTI), a form of pressure ulcers that originates in deep tissue around bony prominences. The present study focused on: (1) obtaining detailed measures of the distribution of pressure experienced by tissue around the ischial tuberosities, and (2) investigating the effectiveness of intermittent electrical stimulation (IES), a novel strategy for the prevention of DTI, in alleviating pressure in regions at risk of breakdown due to sustained loading. The experiments were conducted in adult pigs. Five animals had intact spinal cords and healthy muscles and one had a spinal cord injury that led to substantial muscle atrophy at the time of the experiment. A force-controlled servomotor was used to load the region of the buttocks to levels corresponding to 25%, 50% or 75% of each animal's body weight. A pressure transducer embedded in a catheter was advanced into the tissue to measure pressure along a three dimensional grid around the ischial tuberosity of one hind leg. For all levels of external loading in intact animals, average peak internal pressure was 2.01 ± 0.08 times larger than the maximal interfacial pressure measured at the level of the skin. In the animal with spinal cord injury, similar absolute values of internal pressure as that in intact animals were recorded, but the substantial muscle atrophy produced larger maximal interfacial pressures. Average peak internal pressure in this animal was 1.43 ± 0.055 times larger than the maximal interfacial pressure. Peak internal pressure was localized within a ±2 cm region medio-laterally and dorso-ventrally from the bone in intact animals and ±1 cm in the animal with spinal cord injury. IES significantly redistributed internal pressure, shifting the peak values away from the bone in spinally intact and injured animals. These findings provide critical information regarding the relationship between internal and interfacial pressure around the ischial tuberosities during loading levels equivalent to those experienced while sitting. The information could guide future computer models investigating the etiology of DTI, as well as inform the design and prescription of seating cushions for people with reduced mobility. The findings also suggest that IES may be an effective strategy for the prevention of DTI.

Mechanostimulation, electrostimulation and force measurement in an in vitro model of the isolated rat diaphragm

In an in vitro model of the entire rat diaphragm, diaphragmatic contraction forces at defined preload levels were investigated. A total of 24 excised rat diaphragms were electrically stimulated inside a two-chamber strain-applicator. The resulting contraction forces were determined on eight adjusted preload levels via measuring the elicited pressure in the chamber below the diaphragm. Subsequently, diaphragms were exposed for 6 h to one of four treatments: (1) control, (2) cyclic mechanical stretch, (3) intermittent electrical stimulation or (4) combination of cyclic mechanical stretch and electrical stimulation. Diaphragmatic contraction force increased from 116 ± 21 mN at the lowest preload level to 775 ± 85 mN at the maximal preload level. After 6 h maximal muscle contraction forces were smallest after non-electrostimulated treatment (control: 81 ± 15 mN, mechanical deflection: 94 ± 12 mN) and largest after electrostimulation treatment (mere electrostimulation: 165 ± 20 mN, combined mechano- and electro-stimulation: 164 ± 14 mN). We conclude that our model allows force measurements on isolated rat diaphragms. Furthermore, we conclude that by intermediate electrical stimulation diaphragmatic force generation was better preserved than by mechanical stimulation.

A new choice for the treatment of epilepsy: Electrical auricula-vagus-stimulation

Preliminary reports have suggested that chronic, intermittent electrical stimulation of the cervical vagus nerve (VNS) is an effective treatment for patients who suffered from medically refractory epilepsy. But the traditional VNS is an invasive and implantable procedure that will bring some injury to the patient. Anatomic studies have confirmed the existence of auricular branch of the vagus nerve—Arnold nerve. The Arnold nerve mainly consists of afferent fibers and the superficial sites of the Arnold nerve are optimal for electrical stimulation. We hypothesized that electrical auricula-vagus-stimulation could be a new choice for the treatment of epilepsy.

Asymmetrical changes in lumbar sympathetic nerve activity following stimulation of the sciatic nerve in rat

Noxious stimulation of the leg increases hind limb blood flow (HBF) to the ipsilateral side and decreases to the contralateral in rat. Whether or not this asymmetrical response is due to direct control by sympathetic terminals or mediated by other factors such as local metabolism and hormones remains unclear. The aim of this study was to compare responses in lumbar sympathetic nerve activity, evoked by stimulation of the ipsilateral and contralateral sciatic nerve (SN). We also sought to determine the supraspinal mechanisms involved in the observed responses. In anesthetized and paralyzed rats, intermittent electrical stimulation (1 mA, 0.5 Hz) of the contralateral SN evoked a biphasic sympathoexcitation. Following ipsilateral SN stimulation, the response is preceded by an inhibitory potential with a latency of 50 ms ( N = 26). Both excitatory and inhibitory potentials are abolished following cervical C1 spinal transection ( N = 6) or bilateral microinjections of muscimol ( N = 6) in the rostral ventrolateral medulla (RVLM). This evidence is suggestive that both sympathetic potentials are supraspinally mediated in this nucleus. Blockade of RVLM glutamate receptors by microinjection of kynurenic acid ( N = 4) selectively abolished the excitatory potential elicited by ipsilateral SN stimulation. This study supports the physiological model that activation of hind limb nociceptors evokes a generalized sympathoexcitation, with the exception of the ipsilateral side where there is a withdrawal of sympathetic tone resulting in an increase in HBF.

The Effects of Intermittent Electrical Stimulation on the Prevention of Deep Tissue Injury: Varying Loads and Stimulation Paradigms

A pressure ulcer is a medical complication that arises in persons with decreased mobility and/or sensation. Deep pressure ulcers starting at the bone-muscle interface are the most dangerous, as they can cause extensive damage before showing any signs at the skin surface. We previously proposed a novel intervention called intermittent electrical stimulation (IES) for the prevention of deep tissue injury (DTI). In this study, we tested the effects of four paradigms of IES and one conventional pressure relief paradigm in preventing the formation of deep pressure ulcers in rats. Loading equivalent to 18, 28, or 38% of the body weight (BW) of each rat was applied to the triceps surae muscle in one hind limb. Treatment groups received IES every 10 min for either (i) 5 or 10 s with moderate or maximal contraction, or (ii) complete pressure removal every 10 min for 10 s (conventional pressure relief). The results showed that conventional pressure relief, emulating a wheelchair push-up every 10 min, was inadequate for the prevention of DTI. In contrast, all IES paradigms were equally effective in significantly reducing the extent of deep muscle damage caused by 28 or 38% BW pressure application. These findings suggest that, in conjunction with existing techniques, IES may be an effective intervention for the prophylactic prevention of DTI.

Effects of Intermittent Electrical Stimulation on Superficial Pressure, Tissue Oxygenation, and Discomfort Levels for the Prevention of Deep Tissue Injury

The overall goal of this project is to develop effective methods for the prevention of deep tissue injury (DTI). DTI is a severe type of pressure ulcer that originates at deep bone-muscle interfaces as a result of the prolonged compression of tissue. It afflicts individuals with reduced mobility and sensation, particularly those with spinal cord injury. We previously proposed using a novel electrical stimulation paradigm called intermittent electrical stimulation (IES) for the prophylactic prevention of DTI. IES-induced contractions mimic the natural repositioning performed by intact individuals, who subconsciously reposition themselves as a result of discomfort due to prolonged sitting. In this study, we investigated the effectiveness of various IES paradigms in reducing pressure around the ischial tuberosities, increasing tissue oxygenation throughout the gluteus muscles, and reducing sitting discomfort in able-bodied volunteers. The results were compared to the effects of voluntary muscle contractions and conventional pressure relief maneuvers (wheelchair push-ups). IES significantly reduced pressure around the tuberosities, produced significant and long-lasting elevations in tissue oxygenation, and significantly reduced discomfort produced by prolonged sitting. IES performed as well or better than both voluntary contractions and chair push-ups. The results suggest that IES may be an effective means for the prevention of DTI.

Intermittent electrical stimulation redistributes pressure and promotes tissue oxygenation in loaded muscles of individuals with spinal cord injury

Deep tissue injury (DTI) is a severe form of pressure ulcer that originates at the bone-muscle interface. It results from mechanical damage and ischemic injury due to unrelieved pressure. Currently, there are no established clinical methods to detect the formation of DTI. Moreover, despite the many recommended methods for preventing pressure ulcers, none so far has significantly reduced the incidence of DTI. The goal of this study was to assess the effectiveness of a new electrical stimulation-based intervention, termed intermittent electrical stimulation (IES), in ameliorating the factors leading to DTI in individuals with compromised mobility and sensation. Specifically, we sought to determine whether IES-induced contractions in the gluteal muscles can 1) reduce pressure in tissue surrounding bony prominences susceptible to the development of DTI and 2) increase oxygenation in deep tissue. Experiments were conducted in individuals with spinal cord injury, and two paradigms of IES were utilized to induce contractions in the gluteus maximus muscles of the seated participants. Changes in surface pressure around the ischial tuberosities were assessed using a pressure-sensing mattress, and changes in deep tissue oxygenation were indirectly assessed using T₂*-weighted magnetic resonance imaging (MRI) techniques. Both IES paradigms significantly reduced pressure around the bony prominences in the buttocks by an average of 10-26% (P < 0.05). Furthermore, both IES paradigms induced significant increases in T₂* signal intensity (SI), indicating significant increases in tissue oxygenation, which were sustained for the duration of each 10-min trial (P < 0.05). Maximal increases in SI ranged from 2-3.3% (arbitrary units). Direct measurements of oxygenation in adult rats revealed that IES produces up to a 100% increase in tissue oxygenation. The results suggest that IES directly targets factors contributing to the development of DTI in people with reduced mobility and sensation and may therefore be an effective method for the prevention of deep pressure ulcers.

Carotid sinus nerve stimulation, but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia

We tested the hypothesis that exposure to neonatal intermittent hypoxia (n-IH) in rat pups alters central integrative processes following acute and intermittent peripheral chemoreceptor activation in adults. Newborn male rats were exposed to n-IH or normoxia for 10 consecutive days after birth. We then used both awake and anesthetized 3- to 4-mo-old rats to record ventilation, blood pressure, and phrenic and splanchnic nerve activities to assess responses to peripheral chemoreflex activation (acute hypoxic response) and long-term facilitation (LTF, long-term response after intermittent hypoxia). In anesthetized rats, phrenic and splanchnic nerve activities and hypoxic responses were also recorded with or without intact carotid body afferent signal (bilateral chemodenervation) or in response to electrical stimulations of the carotid sinus nerve. In awake rats, n-IH alters the respiratory pattern (higher frequency and lower tidal volume) and increased arterial blood pressure in normoxia, but the ventilatory response to repeated hypoxic cycles was not altered. In anesthetized rats, phrenic nerve responses to repeated hypoxic cycles or carotid sinus nerve stimulation were not altered by n-IH; however, the splanchnic nerve response was suppressed by n-IH compared with control. In control rats, respiratory LTF was apparent in anesthetized but not in awake animals. In n-IH rats, respiratory LTF was not apparent in awake and anesthetized animals. Following intermittent electrical stimulation, however, phrenic LTF was clearly present in n-IH rats, being similar in magnitude to controls. We conclude that, in adult n-IH rats: 1) arterial blood pressure is elevated, 2) peripheral chemoreceptor responses to hypoxia and its central integration are not altered, but splanchnic nerve response is suppressed, 3) LTF is suppressed, and 4) the mechanisms involved in the generation of LTF are still present but are masked most probably as the result of an augmented inhibitory response to hypoxia in the central nervous system.

Expression of c‐Fos protein in the nucleus of tractus solitary (NTS) and paraventricular nucleus of the hypothalamus (PVN) elicited by electrical stimulation of the aortic depressor nerve in conscious L‐NAME‐induced hypertensive rats

To detect possible alterations of the baroreflex arch, we assessed the expression of c‐Fos in the NTS and PVN of L‐NAME‐induced hypertensive rats submitted to electrical stimulation of the aortic depressor nerve (ADN) in conscious state. Rats were treated for 14 days with L‐NAME (n=7), D‐NAME (n=5) or tap water (CONTROL; n=6). The animals were equipped with catheters in the femoral artery and vein, and a pair of electrodes for intermittent (5s on/10s off) electrical stimulation (1mA, 2ms and 60Hz) during 20 min. L‐NAME treated rats showed higher arterial pressure and heart rate than D‐NAME and CONTROL rats. The hypotensive response and bradycardia due to electrical stimulation did not differ among groups. The density of c‐Fos in the intermediate and commissural caudal NTS, and magnocelular and parvocelular portions of the PVN was higher in L‐NAME treated rats. In conclusion, electrical stimulation of the ADN activated more effectively neurons in the NTS and PVN of L‐NAME induced hypertensive rats. These findings suggest a greater buffering effect of the NTS upon the PVN in this hypertensive model.Supported by CAPES, CNPq and FAPESP.

Vagus nerve stimulation and magnet use: Optimizing benefits

More than 10 years ago, the vagus nerve stimulator became the first device approved by the Food and Drug Administration for use in persons with epilepsy. The vagus nerve stimulator has subsequently served to spearhead the concept of neurostimulation for seizures. Chronic intermittent electrical stimulation of the left vagus nerve is the foundation for vagus nerve stimulation, yet little is known about its capability to deliver acute, on-demand, activation of stimulation through use of a magnet. Thus far, clinical use of magnet-induced vagus nerve stimulation has not been elucidated. In an effort to help guide management, we highlight current and potential uses of acute abortive therapy with vagus nerve stimulation. We review the current evidence that is available for vagus nerve stimulator magnet use, discuss potential clinical applications that exist, offer a protocol for magnet application within the institutional setting, provide our approach to titrating the magnet parameters, and make recommendations for magnet use that support an evolving standard of care.

S2090 Food Intake and Body Weight Effects of Intermittent vs. Continuous Gastric Electrical Stimulation (GES) in Obese Rats

S2090 Food Intake and Body Weight Effects of Intermittent vs. Continuous Gastric Electrical Stimulation (GES) in Obese Rats

Prevention of Venous Thromboembolism

Of the various prophylactic agents evaluated, four have been found to be effective. These are oral anticoagulants, low-dose heparin, mechanical devices which increase venous blood-flow in the leg, and Dextran. Oral anticoagulants have been shown to be effective in patients having abdominal, thoracic, or hip surgery, when treatment was started either before surgery or in the immediate postoperative period. They have also been shown to be effective in medical patients. The evidence derives from studies which showed that treatment can reduce total mortality, prevents venous thromboembolism detected clinically or at autopsy, and prevents thrombosis diagnosed with venography. On the other hand, the incidence of thrombosis diagnosed by 125I-fibrinogen scanning was not reduced when oral anticoagulants were started just before or just after surgery. This suggests that oral anticoagulant treatment starting in the immediate postoperative period may not prevent formation of the initial thrombotic nidus, but is clinically effective because it prevents extension of the nidus to form a significant thrombus. Bleeding has been a significant complication in almost all studies of surgical patients, and this is the major factor which has prevented widespread use of oral anticoagulant prophylaxis. In addition, the need for careful laboratory monitoring makes this approach inconvenient and adds to its expense. Low-dose heparin has been shown to be effective in general surgical and medical patients, but results have been inconclusive in patients having elective hip surgery, and this approach is probably ineffective in patients with hip fracture. In general surgical patients, low-dose heparin prophylaxis has been shown to prevent pulmonary embolism diagnosed at autopsy examination or with lung scanning, and calf and thigh vein thrombosis diagnosed with 125I-fibrinogen leg-scanning. A slight, but statistically significant, increase in the frequency of wound hematoma and a greater postoperative hematocrit fall have been reported when heparin was given three times daily, but not with the twice daily heparin injection regimen. In these studies, low-dose heparin was given without laboratory control of its anticoagulant effect, so that this prophylactic approach is simple, but the need for subcutaneous injections is a disadvantage of this approach. Results with methods which increase venous blood-flow in the leg have varied, depending on the technic used. Active measures, such as intermittent pneumatic calf compression or peroperative electrical calf muscle stimulation, have been shown to prevent thrombosis detected with 125I-fibrinogen leg-scanning. However, while the evidence suggests that both methods are effective in relatively low risk patients, they may have limited value in the high risk patient who is confined to bed for a long time. These methods are free of side effects and relatively inexpensive, but intermittent calf compression, in particular, is slightly cumbersome...

Suppression of Noxious-Induced C-Fos Expression in the Rat Lumbar Spinal Cord by Isoflurane Alone or Combined with Fentanyl

Although our understanding of nociceptive processing during anesthesia has increased greatly over the last decade, many patients still experience hyperalgesia and acute pain postoperatively. The noxious-induced withdrawal reflex (NIWR) model is specifically designed and validated to quantitatively study the reaction on painful, multimodal stimuli in animals under anesthetic conditions. Since the anesthetic mechanisms differ between inhaled anesthetics and opioids, we evaluated the differential effects of isoflurane and fentanyl on c-fos expression at the lumbar level as a measure of nociceptive information transfer during general anesthesia. The experimental setup consisted of a randomized block design with four experimental groups: two light (3/4) minimum alveolar concentration (MAC) isoflurane anesthesia groups (unstimulated/NIWR-stimulated) and two NIWR-stimulated surgical anesthesia groups (1(1/2) MAC isoflurane anesthesia and (3/4) MAC isoflurane anesthesia combined with fentanyl 400-600 microg x kg(-1) x h(-1)). After 2 h of intermittent electrical stimulation of the hind paw of the rat, the number of Fos immunoreactive (Fos-IR) neurons in the dorsal horn was measured quantitatively. The main suppressive effects on lumbar c-fos expression of isoflurane were observed in the superficial lamina II (P = 0.02), whereas fentanyl showed the strongest effects in lamina V (P = 0.05). This study demonstrates that the NIWR model combined with spinal Fos-immunoreactivity is a suitable and useful model for evaluating the differential effects of inhaled anesthetics and opioids on nociceptive information transfer during general anesthesia.