Pilot study evaluating the efficacy of exergaming for the prevention of deep venous thrombosis.

OBJECTIVE: Current prophylactic protocols fail to prevent deep venous thrombosis (DVT) in a significant minority of patients, and it remains one of the leading causes of preventable death. We therefore quantified the efficacy of novel game-based exercises (exergaming) to augment femoral venous parameters relative to ankle movement and muscle flexion. METHODS: Healthy volunteers were recruited to perform a series of ankle and foot exercises using a wireless foot sensor (LEGSys; BioSensics LLC, Watertown, Mass) to navigate a computer cursor sequentially on a screen to the center of 200 circular targets. A single ultrasound technician (W.A.M.) measured each patient's mean flow volume, peak flow velocity, mean flow velocity, and cross-sectional area of the right femoral vein at baseline and obtained immediate postexercise (PEX), 5-minute PEX, and 15-minute PEX measurements. Electromyography (EMG) was performed at baseline and during the exercise. Baseline demographics and medical and surgical comorbidities were also recorded. The primary end point was the difference between baseline and immediate PEX mean flow volume estimates. We secondarily explored the association of baseline characteristics and EMG measurements with femoral vein parameters. RESULTS: Fifteen healthy subjects (53% male; 28.1 ± 4.6 years) completed the exergaming task within a mean of 4 minutes, 2 ± 21 seconds. Immediately after exercise, the femoral vein mean flow volume, mean velocity, and peak systolic velocity increased by 49%, 53%, and 48%, respectively (P < .02 for each). Mean flow volume and velocity remained significantly elevated 5 minutes after exercise (P < .04 for each). Plantar flexion and dorsiflexion velocities and EMG frequency and intensity were not significantly correlated with PEX mean flow volume estimates (P > .05). Subgroup analysis revealed that women (P < .01) and Hispanics (P < .01) exhibited significantly slower PEX responses. Subjects with the largest improvements in mean flow volume had lower peak plantar flexion velocities (P < .01). CONCLUSIONS: Exergaming increases mean flow volume, mean flow velocity, and peak systolic velocity within the femoral vein by approximately 50% above baseline. Exergaming represents a novel and potentially attractive method of DVT prevention by augmenting femoral vein mean volume flow and capitalizing on biofeedback. Less forceful but more uniform contractions were found to be most effective at augmenting venous blood flow. Exergaming will require further validation in larger study bases, among patients at higher risk of DVT.

Randomised Controlled Trial: Potential Benefit of a Footplate Neuromuscular Electrical Stimulation Device in Patients with Chronic Venous Disease.

OBJECTIVES: Chronic venous disease (CVD) is common, affecting a quarter of the population. Current conservative methods of treatment aim to prevent progression of disease by reducing ambulatory venous pressure. Neuromuscular electrical stimulation (NMES) refers to the use of electrical impulses to elicit muscle contraction. This pilot randomised controlled trial investigates the effect of a footplate NMES device (REVITIVE) on venous flow parameters, limb oedema, and quality of life outcome measures in patients with CVD. METHODS: Twenty-two patients with Clinical Etiological Anatomical and Pathophysiological (CEAP) clinical class C2-C4 venous disease were randomised to receive a sham or test device. The recommended duration of use was for 30 minutes daily for 6 weeks. Venous flow parameters (duplex ultrasound), limb volume (optoelectric volumeter), and quality of life outcome measures were measured at baseline and after 6 weeks. RESULTS: The mean age of participants was 62 years, body mass index 28.6, with a 15:7 female preponderance. There was a significant difference in the percentage change in femoral vein flow parameters (from baseline) between the test and sham group while using the device (Week 0 time-averaged mean velocity 102.4% vs. -9.1%, p < .0001; volume flow 107.9% vs. -3.7%, p < .0001; peak velocity 377.7% vs. -6.7%, p < .0001). Limb volume was observed to increase significantly in the sham group (2.0% at Week 0 and 1.2% at Week 6; p < .01). This was prevented in the test group (+0.8% at Week 0 and 1.0% at Week 6; p = .06). There was a significant difference in the Aberdeen Varicose Vein Questionnaire between the two groups over the 6 weeks. CONCLUSIONS: This trial demonstrated a significant difference in venous flow parameters and prevention of orthostatic limb oedema with NMES. There was a positive effect on quality of life. Larger studies are required to determine the clinical significance of this in patients with venous disease.

The effect of footplate neuromuscular electrical stimulation on venous and arterial haemodynamics.

OBJECTIVE: This pilot study aims to determine the effect of the Revitive™ footplate neuromuscular electrical stimulation device on venous and arterial haemodynamic changes in healthy individuals. METHOD: The blood flow (cc/min) and time averaged mean velocity (cm/s) of the superficial femoral vein and artery were measured using ultrasound at baseline, 15 min during, and immediately after cessation of the 30 min stimulation cycle. Data were analysed using the Wilcoxon matched-pairs signed rank test. RESULTS: Venous and arterial duplex ultrasound haemodynamic measurements were taken in 10 and 20 healthy volunteers, respectively. Mean age 38.7 (range 21-64), ankle brachial pressure index 0.9-1.0. At 15 min, there was a significant increase in venous median blood flow (88.3 cc/min, p = 0.014) and an increase in time averaged mean velocity (1.13 cm/s, p = 0.065) compared to baseline. Similarly, there was a significant increase in arterial median blood flow (38.7 cc/min, p < 0.0001) and time averaged mean velocity (2.21 cm/s, p = 0.0003) at 15 min compared to baseline. There was no significant difference in venous or arterial measurements compared to baseline after stimulation cessation. CONCLUSIONS: Blood flow and time averaged mean velocity increased during neuromuscular electrical stimulation but returned to baseline once stimulation had stopped. By improving blood flow, neuromuscular electrical stimulation has the ability to enhance venous return, counteract venous stasis and improve limb arterial inflow.

Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists.

The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,ß-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferent-mediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.

Systemic fatty acid responses to transient focal cerebral ischemia: influence of neuroprotectant therapy with human albumin.

Human albumin therapy is highly neuroprotective in focal cerebral ischemia. Because albumin is the main carrier of free fatty acids (FFA) in plasma, we investigated the content and composition of plasma FFA in jugular vein (JV), femoral artery (FA) and femoral vein (FV) of rats given intravenous human albumin (1.25 g/kg) or saline vehicle (5 mL/kg) 1 h after a 2 h middle cerebral artery occlusion (MCAo) or sham surgery. Arachidonic acid was the only FFA significantly increased by MCAo in all plasma samples prior to albumin administration, remaining at the same level regardless of subsequent treatments. Albumin treatment induced in both MCAo- and sham-groups a 1.7-fold increase in total plasma FFA (mainly 16:0, 18:1, 18:2n-6) during 90-min reperfusion. MCAo selectively stimulated the albumin-mediated mobilization of n-3 polyunsaturated fatty acids (PUFA), with an early increase in 22:5n-3 and 22:6n-3 in the FA prior to detectable changes in the JV. In the MCAo-albumin group, the lower level of FFA in JV as compared with FA and FV suggests an albumin-mediated systemic mobilization and supply of FFA to the brain, which may favor the replenishment of PUFA lost from cellular membranes during ischemia and/or to serve as an alternative source of energy, thus contributing to albumin neuroprotection.

[Pharmacological properties od steroid glycosides from Ruscus ponticus]. / Farmakologicheskie svoistva steroidnykh glikozidov Ruscus ponticus.

Some pharmacological properties of the sum of steroidal glycosides (ruscoponin preparation) extracted from underground parts of Ruscus ponticus were studied. The drug exhibits a pronounced antiexudative effect (related to the alpha 1-adrenergic activity) on the models of formalin edema and pouch granuloma in rats and a thermal rectum inflammation in mice. The drug exhibited no hepato-, nephro-, and gastrotoxicity.

Electrical foot stimulation and implications for the prevention of venous thromboembolic disease.

BACKGROUND: Venous stasis caused by immobility is an important risk factor for deep vein thrombosis following surgery and lower limb trauma, in bed-ridden medical patients, and in high-risk long distance air travelers. A safe and convenient method for reducing venous stasis would be useful in patients while in hospital and after discharge during their rehabilitation. SUBJECTS AND METHODS: 49 healthy subjects aged 51-76 were seated for 4 hours during which they received mild electrical stimulation of the calf, or sole of the foot (plantar muscles). Popliteal and femoral venous blood flow velocities were measured via doppler ultrasound. The non-stimulated lower extremity served as the simultaneous control. Subjects completed a questionnaire regarding their acceptance and tolerance of the electrical stimulation. RESULTS: There was a significant increase in venous femoral and popliteal blood flow for both calf (p < 0.035, p < 0.003), and plantar muscles (p < 0.0001, p < 0.009) on the stimulated side compared to the unstimulated side. The magnitude of the effect was similar for calf and plantar muscle stimulation. Subjects did not find the experience uncomfortable, and would use an electrical stimulator if told by their physician that they were at risk for developing blood clots. CONCLUSIONS: Mild electrical stimulation of the feet, as well as the calf, is a safe effective and convenient method for counteracting venous stasis and therefore has the potential to reduce the risk of deep vein thrombosis and pulmonary embolism for subjects who are immobilized.

Vago-sympathoadrenal reflex in thermogenesis induced by osmotic stimulation of the intestines in the rat.

Duodenal infusion of hypertonic solutions elicits osmolality-dependent thermogenesis in urethane-anaesthetized rats. Here we investigated the involvement of the autonomic nervous system, adrenal medulla and brain in the mechanism of this thermogenesis. Bilateral subdiaphragmatic vagotomy greatly attenuated the first hour, but not the later phase, of the thermogenesis induced by 3.6 % NaCl (10 ml kg(-1)). Neither atropine pretreatment (10 mg kg(-1), I.P.) nor capsaicin desensitization had any effect on the osmotically induced thermogenesis, suggesting the involvement of non-nociceptive vagal afferents. Bilateral splanchnic denervation caudal to the suprarenal ganglia also had no effect, suggesting a lack of involvement of spinal afferents and sympathetic efferents to the major upper abdominal organs. Adrenal demedullation greatly attenuated the initial phase, but not the later phase, of thermogenesis. Pretreatment with the beta-blocker propranolol (20 mg kg(-1), I.P.) attenuated the thermogenesis throughout the 3 h observation period. The plasma adrenaline concentration increased significantly 20 min after osmotic stimulation but returned to the basal level after 60 min. The plasma noradrenaline concentration increased 20 min after osmotic stimulation and remained significantly elevated for 120 min. Therefore, adrenaline largely mediated the initial phase of thermogenesis, and noradrenaline was involved in the entire thermogenic response. Moreover, neither decerebration nor pretreatment with the antipyretic indomethacin (10 mg kg(-1), S.C.) had any effect. Accordingly, this thermogenesis did not require the forebrain and was different from that associated with fever. These results show the critical involvement of the vagal afferents, hindbrain and sympathoadrenal system in the thermogenesis induced by osmotic stimulation of the intestines.

Effect of dobutamine on skeletal muscle metabolism in patients with congestive heart failure.

Dobutamine is known to increase leg blood flow during exercise in patients with heart failure. However, it is uncertain whether the increased flow is delivered to working skeletal muscle. In 7 patients with heart failure, the effects of dobutamine were examined on calf phosphorus-31 magnetic resonance spectroscopy (MRS) spectra and femoral vein blood flow during rest and upright plantar flexion. During upright plantar flexion every 3 seconds, dobutamine increased femoral venous blood flow (control 1.7 +/- 0.1; dobutamine 2.1 +/- 1.0 liters/min; p less than 0.05) and increased femoral venous O2 saturation (control 24 +/- 5%; dobutamine 31 +/- 2%; p less than 0.05), indicating improved total leg blood flow. However, dobutamine did not change the slope of the relation between systemic VO2 and the calf inorganic phosphate to phosphocreatine relation (control 0.0054 +/- 0.0039; dobutamine 0.0056 +/- 0.0032; difference not significant) and did not change muscle pH, suggesting no improvement in blood flow to active skeletal muscle. These findings suggest that dobutamine does not improve oxygen delivery to working skeletal muscle in patients with heart failure, despite its ability to increase cardiac output and limb blood flow.

Endothelium-dependent relaxation in response to aggregating platelets in porcine femoral veins and its modulation by diet.

The present study examined the protective role of the venous endothelium against aggregating platelets and its modulation by diet. Yorkshire pigs were fed a regular chow (control pigs), 2% high-cholesterol diet (for 10 weeks, cholesterol-fed pigs), and regular chow plus cod-liver oil (30 ml/day for 4 weeks, oil-fed pigs). Endothelium-dependent responses were examined in vitro in rings of femoral veins in the presence of the inhibitor of cyclooxygenase indomethacin. In control pigs, aggregating platelets, serotonin, and ADP caused endothelium-dependent relaxations. The platelet-induced relaxations were attenuated by methiothepin (a combined 5-HT1 and 5-HT2 serotonergic blocker) or apyrase (an ADPase and ATPase) and were abolished by the combination of the two agents. In quiescent rings, platelets caused contractions, which were reduced in the presence of endothelium; the contractions were prevented by ketanserin (a 5-HT2 serotonergic blocker) or methiothepin but not by R 68 070 (a thromboxane A2 receptor blocker) or dazoxiben (a thromboxane-synthetase blocker). In cholesterol-fed pigs, the platelet-induced relaxations were not altered, whereas in oil-fed pigs, the endothelium-dependent relaxations to platelets, serotonin, and ADP were augmented. Platelet-induced contractions were significantly reduced in rings with endothelium from oil-fed pigs, whereas the contractions were comparable in rings without endothelium among the three groups. Endothelium-dependent relaxations in response to the calcium ionophore A23187, direct relaxations in response to sodium nitroprusside, and direct contractions in response to potassium chloride were comparable among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of isolated canine and simian femoral arteries and veins to phenylephrine, xylazine and KCl after removal of endothelium.

Using the cannula inserting method, vasoconstrictor responses to phenylephrine (an alpha 1-adrenoreceptor agonist), xylazine (an alpha 2-adrenoreceptor agonist) and KCl after removal of the endothelium by intraluminal treatment with saponin were investigated in isolated and perfused canine and simian femoral arteries and veins. In arteries, vasoconstrictor responses to KCl were markedly potentiated by removal of the endothelium in both species. KCl-induced vasoconstrictions were not modified by treatment with an alpha 1-adrenoreceptor antagonist, bunazosin, which blocked noradrenaline-induced constrictions. The phenylephrine-induced constriction was significantly potentiated by removal of the endothelium in simian arteries but not in canine arteries. In both arteries, responses to xylazine were not influenced by removal of the endothelium. In femoral veins of both species, responses to phenylephrine, xylazine and KCl were not significantly modified by a relatively small dose of saponin but were moderately depressed by a large dose. It is suggested that the endothelium may play an important role for inducing alpha 1-adrenoreceptor-mediated constrictor responses in simian femoral arteries, but not in canine arteries or in either vein tested.