Sensory impairment: a feature of chronic venous insufficiency.
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OBJECTIVE: Clinical and microscopic evidence suggests the existence of sensory neuropathy in patients with severe chronic venous insufficiency (CVI). A clinical evaluation was conducted to determine whether a sensory neuropathy was present and, if so, to determine its extent and distribution. METHODS: The study was performed in a university-affiliated Veterans Affairs Medical Center. Twenty-three limbs were studied in 14 male veterans with mild or moderate CVI. The exclusions included diabetes, previous ipsilateral extremity surgery, or other diseases associated with neuropathy. Sensory thresholds in the limbs with CEAP class 2 disease (n = 11) were compared with the thresholds in the limbs with CEAP class 5 disease (n = 12) at nine different sites on the foot, ankle, calf, thigh, and palm. Thenar and hypothenar thresholds were measured as internal controls. Thresholds were determined by a pressure aesthesiometer consisting of 20 graduated filaments that ranged from 1.65 to 6.65 (log(10)mg)(10) of pressure. A complete, sensory motor assessment of the limb was performed by an experienced neurosurgeon who specialized in peripheral nerve evaluation. The clinical variables assessed were deep tendon reflexes, vibration, proprioception, and light touch. Venous reflux was determined with duplex ultrasound scanning and air plethysmography. RESULTS: Sensory thresholds at the most common site of venous ulceration-just proximal to the medial malleolus--were significantly (P <.05) different between mild (class 2) and severe (class 5) CVI. Sensory abnormalities coincided with the extent of trophic changes and did not reflect specific dermatomal or cutaneous nerve distributions. In addition to light touch or pinprick, vibration sense and deep tendon reflexes were also significantly worse in those with severe CVI. CONCLUSION: Sensory neuropathy is a feature of severe CVI, and its distribution is coincident with trophic changes. Because this is often unappreciated by the patient, it probably contributes to the propensity for deterioration from minor trauma. (+info)
Exercise training increases basal nitric oxide production from the forearm in hypercholesterolemic patients.
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The objective of this study was to investigate the effects of cycle training on basal nitric oxide (NO) production and endothelium-dependent dilator capacity in hypercholesterolemic patients in whom acetylcholine responsiveness is impaired. Nine sedentary hypercholesterolemic volunteers (total plasma cholesterol >6.0 mmol/L; 2 female) aged 44+/-3 years (mean+/-SEM) participated in the study. Subjects remained sedentary for 4 weeks and performed 4 weeks of home-based cycle training (3 x 30 minutes/week at 65% maximum oxygen consumption [VO(2)max]) in a randomized order. Arteriovenous nitrate/nitrite (NO(x)) gradient was assessed and plethysmography was used to measure the forearm blood flow responses to arterial infusions of acetylcholine, sodium nitroprusside, and N(G)mono methyl L-arginine. Training increased VO(2)max from 30.4+/-1.9 to 34.3+/-1.4 mL x kg(-1) x min(-1) (P=0.01). Intrabrachial diastolic blood pressure was reduced from 70+/-3 to 68+/-3 mm Hg (P=0.02) with training, whereas systolic pressure did not change. Plasma triglycerides and total, LDL, and HDL cholesterol were not different between interventions. In the sedentary state, there was a positive forearm arteriovenous difference in plasma NO(x) indicating net extraction (6.8+/-4.0 nmol x 100 mL(-1) x min(-1)), whereas in the trained state this difference was negative, indicating net production (-5.8+/-5.8 nmol x 100 mL(-1) x min(-1); P=0.03). N(G)mono methyl L-arginine, at a dose of 4 micromol/min, caused a greater vasoconstriction after training (79.6+/-3.4% versus 69.9+/-6.8%; P=0.05). Acetylcholine and sodium nitroprusside induced dose-dependent elevations in forearm blood flow that were unaffected by training. These data suggest that basal release of endothelium-derived NO is increased with 4 weeks of home based training in hypercholesterolemic patients, independently of lipid profile modification. This may contribute to the cardiovascular protective effects of exercise training, including reduced blood pressure. (+info)
Basal and exercise-induced skeletal muscle blood flow is augmented in type I diabetes mellitus.
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Hyperaemia occurs early in the renal and retinal microcirculation of patients with type I (insulin-dependent) diabetes mellitus, and may be critical in the development of nephropathy and retinopathy. We therefore sought to determine whether resting and exercise-induced hyperaemia was also apparent in the skeletal muscle circulation of young subjects with type I diabetes. Blood flow was assessed by venous occlusion plethysmography in 18 diabetic (DM) subjects and 20 matched controls. Exercise entailed 2 min of isotonic exercise against no load. Endothelium-dependent and -independent vasodilator function was assessed following intra-arterial infusion of acetylcholine and sodium nitroprusside respectively. Forearm blood flow (FBF) was higher in DM subjects than in controls (3.3+/-0.3 and 2.2+/-0.2 ml x min(-1) x 100 ml(-1) forearm respectively; P<0.005). This was not due to differences in forearm or body size, blood pressure, heart rate, lipid status or glycaemic control. Peripheral insulin levels were higher in DM subjects than in controls (48.5+/-8 and 15.5+/-1.5 micro-units/ml respectively; P<0.005). Resting FBF was closely correlated with insulin levels (r(2)=0.4; P<0.005). Parameters of exercise-induced hyperaemia [including peak flow (16.4+/-1.4 and 12.0+/-0.7 ml x min(-1) x 100 ml(-1) forearm in DM and control subjects respectively; P<0.01) and the volume repaid to the forearm at 5 min post-exercise (32.1+/-3.1 and 23.1+/-1.4 ml x 100 ml(-1) forearm respectively; P<0.05)] were also significantly greater in DM subjects, even when differences in resting FBF were taken into account. Peak hyperaemic blood flow and the volume repaid at 5 min were also related to insulin levels (r(2)=0.16; P<0.05 and r(2)=0.27; P<0.005 respectively). The vasodilator response to acetylcholine was reduced in DM subjects (P<0.05; analysis of variance), and the slope of this dose-flow relationship was inversely related to insulin levels (r(2)=0.2; P<0.05). These data show that both resting and exercise-induced skeletal muscle blood flow are augmented in young patients with type I diabetes, possibly due to the vasodilatory effect of increased insulin levels. Diminished vasodilator responses to acetylcholine may also, in part, be a consequence of insulin-augmented resting muscle blood flow. (+info)
A modular NIRS system for clinical measurement of impaired skeletal muscle oxygenation.
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Near-infrared spectrometry (NIRS) is a well-known method used to measure in vivo tissue oxygenation and hemodynamics. This method is used to derive relative measures of hemoglobin (Hb) + myoglobin (Mb) oxygenation and total Hb (tHb) accumulation from measurements of optical attenuation at discrete wavelengths. We present the design and validation of a new NIRS oxygenation analyzer for the measurement of muscle oxygenation kinetics. This design optimizes optical sensitivity and detector wavelength flexibility while minimizing component and construction costs. Using in vitro validations, we demonstrate 1) general optical linearity, 2) system stability, and 3) measurement accuracy for isolated Hb. Using in vivo validations, we demonstrate 1) expected oxygenation changes during ischemia and reactive hyperemia, 2) expected oxygenation changes during muscle exercise, 3) a close correlation between changes in oxyhemoglobin and oxymyoglobin and changes in deoxyhemoglobin and deoxymyoglobin and limb volume by venous occlusion plethysmography, and 4) a minimal contribution from movement artifact on the detected signals. We also demonstrate the ability of this system to detect abnormal patterns of tissue oxygenation in a well-characterized patient with a deficiency of skeletal muscle coenzyme Q(10). We conclude that this is a valid system design for the precise, accurate, and sensitive detection of changes in bulk skeletal muscle oxygenation, can be constructed economically, and can be used diagnostically in patients with disorders of skeletal muscle energy metabolism. (+info)
Effects of brain natriuretic peptide on forearm vasculature: comparison with atrial natriuretic peptide.
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OBJECTIVE: The aim of the present study was to determine the vasoactive effects of brain natriuretic peptide (BNP) as compared to those of atrial natriuretic peptide (ANP) in normal man. METHODS: Ten healthy male subjects (median age 21 (20-23) year) were studied twice. In the first study equimolar doses (1, 3, and 10 pmol/dl/min) of both BNP and ANP (in random order and double blind) were infused into the brachial artery of the non-dominant arm with a 1-h wash-out period in between. In the second study two BNP (n = 5) or ANP (n = 5) dose-response curves were performed in order to assess the repeatability of the BNP/ANP infusions. To this end, BNP and ANP were infused in the same equimolar doses as in the first protocol. Forearm blood flow (FBF) was determined by venous occlusion plethysmography before and during infusions. RESULTS: BNP increased the FBF ratio (infused/contralateral arm) by 6%, 17%, and 48%, respectively (p < 0.05), while ANP increased the FBF ratio by 4%, 58%, and 133% (p < 0.001). The slopes of the BNP dose-response curves differed significantly from those of the ANP curves (18.1 versus 43.2; p = 0.022). No differences were observed between the repeated dose-response curves of either BNP or ANP. CONCLUSIONS: The present data demonstrate that BNP induces a dose-dependent vasodilatation in man. On a molar basis, however, this vasodilatation is significantly less than the vasodilatation induced by ANP. These differences may be related to differences in natriuretic-peptide-receptor affinity. Furthermore, our data show that the vasoactive effects of both BNP and ANP are repeatable in time. (+info)
Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation.
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OBJECTIVE: Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia. METHODS: We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-L-arginine (L-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n = 20) and control (n = 20) subjects were age- and gender-matched. RESULTS: Total cholesterol (6.9 +/- 0.3 vs. 4.6 +/- 0.1 mmol/l, P < 0.0001), low density lipoprotein (4.9 +/- 0.4 vs. 2.7 +/- 0.1 mmol/l, P < 0.001) and triglyceride (1.3 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P = 0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1 +/- 1.9 vs. 17.6 +/- 2.2 ml/100 ml/min, P = 0.03), and reduced the peak response to sodium nitroprusside (6.0 +/- 0.4 vs. 8.1 +/- 0.6 ml/100 ml/min, P < 0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1 +/- 1.0 vs. 13.2 +/- 1.0 ml/100 ml/min, P = 1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by L-NMMA to a similar degree (by 33% vs. 40%, P = 0.17) in both groups. Although L-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P = 0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups. CONCLUSIONS: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation. (+info)
Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension.
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Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses (eg, vitamins C and E). A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase. We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age. We examined 23 subjects (11 patients with type 2 diabetes and 12 healthy age-matched control subjects) in 2 parallel groups. The subjects were administered 300 mg allopurinol in a randomized, placebo-controlled study in which both therapies were administered for 1 month. Endothelial function was assessed with bilateral venous occlusion plethysmography, in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured. Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30% (3.16+/-1.21 versus 2.54+/-0.76 mL. 100 mL(-1). min(-1) allopurinol versus placebo; P=0.012, 95% CI 0.14, 1.30) but did not affect the nitroprusside response in patients with type 2 diabetes. There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects. Allopurinol improved endothelial function to near-normal levels. Regarding markers of free radical activity, the level of malondialdehyde was significantly reduced (0.30+/-0.04 versus 0. 34+/-0.05 micromol/L for allopurinol versus placebo, P=0.03) in patients with type 2 diabetes but not in control subjects. The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects. In the former group, allopurinol restored endothelial function to near-normal levels. (+info)
Venous reflux has a limited effect on calf muscle pump dysfunction in post-thrombotic patients.
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The purpose of the present study was to evaluate the relationship between calf muscle pump dysfunction (CMD) and the presence and location of valvular incompetence. Deep vein obstruction might influence CMD, and so venous outflow resistance (VOR) was measured. VOR and calf muscle pump function were measured in 81 patients, 7-13 years after venographically confirmed lower-extremity deep venous thrombosis. The supine venous pump function test (SVPT) measures CMD, and the VOR measures the presence of venous outflow obstructions, both with the use of strain-gauge plethysmography. Valvular incompetence was measured using duplex scanning in 16 vein segments of one leg. Venous reflux was measured in proximal veins using the Valsalva manoeuvre, and in the distal veins by distal manual compression with sudden release. Abnormal proximal venous reflux was defined as a reflux time of more than 1 s, and abnormal distal venous reflux as a reflux time of more than 0.5 s. No statistically significant relationship was found between the SVPT and either the location or the number of vein segments with reflux. Of the 81 patients, only nine still had an abnormally high VOR, and this VOR showed no relationship with the SVPT. In conclusion, venous reflux has a limited effect on CMD, as measured by the SVPT. The presence of a venous outflow obstruction did not significantly influence the SVPT. Duplex scanning and the SVPT are independent complementary tests for evaluating chronic venous insufficiency. (+info)