Description and validation of a novel liquid metal-free device for venous congestion plethysmography.
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We present a newly developed electromechanical sensor with automated calibration for strain-gauge plethysmography (filtrass) and compare it to a conventional mercury-in-Silastic strain-gauge plethysmograph (MSG). Fluid filtration capacity (K(f)) and isovolumetric venous pressure (Piv) of the limb were assessed noninvasively with both devices in 29 healthy volunteers. We found significantly higher K(f) and Piv values with MSG [4.6 +/- 2.0 x 10(-3) ml. min(-1). mmHg(-1). 100 ml tissue(-1) (K(f) units; K(f)U) and 21.2 +/- 8.1 mmHg for Pvi], than with filtrass, giving values of 3.1 +/- 0.8 K(f)U and 15.1 +/- 7.1 mmHg. Because K(f) and Piv are profoundly influenced by the calibration, we investigated the quality of the calibration signal and its impact on the obtained values. We could show that the reproducibility of repeated calibrations was higher with filtrass (58% lower mean +/- SD). The data were grouped according to the quality of calibration, and we found no significant difference in K(f) and Piv between filtrass (3.0 +/- 0.7 K(f)U and 15.9 +/- 6.9 mmHg, respectively) and MSG with good calibration signal (3.3 +/- 0. 8 K(f)U and 18.6 +/- 7.1 mmHg, respectively; no significant difference). However, we obtained significantly higher MSG values (5. 6 +/- 2.0 K(f)U and 23.1 +/- 8.4 mmHg, respectively; P < 0.001) in the group with a bad calibration signal. We suggest that the filtrass sensor, which performs an automatic, standardized calibration procedure and shows a linear signal response to stretch, gives highly reproducible and reliable results and thus is more suitable for routine application. (+info)
Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature.
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OBJECTIVES: The goal of this study was to investigate the mechanism of reduced vasoconstrictor sensitivity to norepinephrine in women compared with men. BACKGROUND: beta2-adrenergic agonists such as albuterol dilate forearm resistance vessels, partly by activating the L-arginine/nitric oxide pathway. Norepinephrine (which acts as beta- as well as alpha-adrenergic receptors) causes less forearm vasoconstriction in women than it does in men. This could be explained by a greater sensitivity to beta2-receptor stimulation in women than in men. METHODS: Forearm blood flow was measured by venous occlusion plethysmography in healthy women (days 10 to 14 of the menstrual cycle) and in men. Drugs were administered via the brachial artery in three separate protocols: albuterol +/- NG-monomethyl-L-arginine (an inhibitor of nitric oxide synthase); substance P, nitroprusside and verapamil (control vasodilators); norepinephrine (+/- propranolol, a beta-adrenergic receptor antagonist). RESULTS: Vasodilator responses to albuterol were greater in women than they were in men (p = 0.02 by analysis of variance). NG-monomethyl-L-arginine reduced these similarly in men and women. Responses to control vasodilators were less in women than they were in men (each p < 0.05). Norepinephrine caused less vasoconstriction in women than it did in men (p = 0.02). Propranolol did not influence basal flow in either gender nor responses of men to norepinephrine but increased vasoconstriction to each dose of norepinephrine in women (p < 0.0001 for interaction between gender and propranolol). Responses to norepinephrine coinfused with propranolol were similar in men and women. CONCLUSIONS: Stimulation of beta2-adrenergic receptors causes greater forearm vasodilation in premenopausal women, at midmenstrual cycle, than it does in men. This is sufficient to explain why vasoconstriction to brachial artery norepinephrine is attenuated in such women. (+info)
Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial.
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OBJECTIVES: This phase I study was designed to evaluate the safety, tolerability and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) and intermittent claudication. We also assessed the effects of basic fibroblast growth factor (bFGF) on calf blood flow as a measure of biologic activity. BACKGROUND: Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind limb ischemia. The safety and efficacy of bFGF in patients is unknown, and early clinical trials are underway in coronary and peripheral arterial disease. METHODS: A double-blind, placebo-controlled, dose-escalation trial was conducted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 microg/kg of bFGF (n = 4), 30 microg/kg of bFGF once (n = 5) and 30 microg/kg of bFGF on two consecutive days (n = 4). Study drug was infused into the femoral artery of the ischemic leg. Detailed safety information including retinal photography for neovascularization were obtained through one year. Calf blood flow was measured with strain gauge plethysmography in the two higher dose treatment groups and in four placebo patients at baseline, one month and three to seven months after treatment. RESULTS: Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean +/- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS: In this initial randomized, double-blind, placebo-controlled trial in patients with atherosclerotic PVD and claudication, bFGF was well-tolerated. The data suggest a salutary biologic effect, and initiation of phase 2 trials is warranted. (+info)
Vasodilator prostanoids, but not nitric oxide, may account for skeletal muscle hyperaemia in Type I diabetes mellitus.
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We and others have previously documented increased resting and exercise-induced skeletal muscle blood flow in young subjects with Type I (insulin-dependent) diabetes mellitus compared with healthy controls. Both NO and prostanoids are important regulators of vascular tone and may therefore contribute to this hyperaemia. The aim of the present study was to determine the contribution of NO and vasodilator prostanoids to this skeletal muscle hyperaemia in diabetes. We assessed the effects of infusion into the intrabrachial artery of the cyclo-oxygenase inhibitor acetylsalicylic acid (ASA; aspirin) and of the L-arginine analogue N(G)-monomethyl-L-arginine (L-NMMA) on skeLetal muscle blood flow in subjects with Type I diabetes mellitus (DM subjects) and control subjects. Blood flow was measured by venous occlusion plethysmography. Isotonic forearm exercise involved 2 min of wrist flexion and extension. Resting flow (forearm blood flow; FBF) was augmented in DM subjects, as was peak exercise-related blood flow (PFBF) and the volume repaid to the forearm 5 min after exercise (AUC 5, where AUC is area under the flow-time curve) (P<0.05), even when accounting for differences in basal flow. Infusion of L-NMMA reduced resting flow by 48% in controls (P<0.005) and by 12% in DM subjects (not significant). L-NMMA reduced PFBF and AUC 5 by 29% (P<0.05) and 39% (P<0.0005) respectively in controls, but had no significant effect on these parameters in DM subjects. Infusion of ASA reduced FBF, PFBF and AUC 5 in both DM (P<0.05) and control (P<0.05) subjects, but the magnitude of this reduction was greater in DM than in control subjects (ANOVA, P<0.05), even when differences in resting FBF were accounted for. Indeed, ASA eliminated the differences in FBF, PFBF and AUC 5 between DM and control subjects. Thus increased release of vasodilator prostanoids, rather than of NO, appears to account for skeletal muscle hyperaemia in Type I diabetes. (+info)
Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon.
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OBJECTIVE: To determine circulating endothelin-1 levels (ET-1) in patients with primary or secondary associated Raynaud's phenomenon (RP) under resting conditions and in response to cold provocation. METHODS: Patients were categorised as primary RP (18) or scleroderma associated RP (14). Finger blood flow was measured by venous occlusion plethysmography at finger temperatures of 32 degrees C and 24 degrees C. Vasospasm was detected as a finger systolic pressure of 0 mm Hg after standardised provocative cooling. Severity of vasospasm was assessed by the level of cooling required to provoke spasm. Plasma ET-1 levels were measured in antecubital blood withdrawn under baseline conditions (finger 32 degrees C) and at the point of vasospasm. Measurements were also made in 19 matched control subjects. RESULTS: Finger blood flow was lower in patients with RP than in controls, with no difference between the two RP groups. Vasospasm occurred in all patients with RP but not in any control subjects and a grading system of severity was established. Baseline plasma ET-1 levels were similar in patients with RP and controls. Increases in ET-1 levels at the point of vasospasm in patients or corresponding timepoint in controls were also similar. There was no significant difference between the ET-1 levels in the two RP subgroups when the fingers were warm or when vasospasm was present. CONCLUSIONS: These results do not support the hypothesis that ET-1 plays a part in the pathogenesis of RP. Objective testing is a useful adjunct to the clinical diagnosis of RP and allows assignment of a severity grade. (+info)
The value of air plethysmography in predicting clinical outcome after surgical treatment of chronic venous insufficiency.
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PURPOSE: The role of air plethysmography (APG) as a predictor of clinical outcome after surgery in venous disease is yet to be defined. The purpose of this study was to investigate the value of APG in predicting clinical outcome after venous surgery for chronic venous insufficiency (CVI). METHODS: Seventy-three extremities in 71 patients with Class 3 through 6 CVI were assessed preoperatively with CEAP (c linical, e tiologic, a natomic, p athophysiologic) criteria, standing reflux duplex ultrasound scan, and APG with measurements of preoperative venous filling index (VFI), venous volumes, ejection fraction, and residual volume fraction. After surgical treatment of the affected limbs, repeat APG studies were obtained within 6 weeks. Established venous reporting standards were used for follow-up to calculate clinical symptom scores (CSSs) in each patient. RESULTS: Superficial venous reflux occurred alone in 24 limbs or in conjunction with perforator incompetence in 26 limbs. Deep and superficial reflux, with or without perforator incompetence, was found in 16 limbs, and seven limbs had isolated deep insufficiency. Follow-up was available in 60 of 71 patients (mean period, 44.3 months). Postoperative APG demonstrated significant hemodynamic changes after surgery as measured with VFI, venous volumes, ejection fraction, and residual volume fraction. Mean CSSs decreased from 7.35 +/- 0.56 preoperatively to 1.79 +/- 0.32 at late follow-up after surgery (P <.001). With the use of logistic regression, the parameter correlating most closely with clinical outcome was the VFI. A normal postoperative VFI (+info)
Bradykinin stimulates tissue plasminogen activator release from human forearm vasculature through B(2) receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway.
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BACKGROUND: Bradykinin stimulates dose-dependent tissue plasminogen activator (tPA) release from human endothelium. Although bradykinin is known to cause vasodilation through B(2) receptor-dependent effects on NO, prostacyclin, and endothelium-derived hyperpolarizing factor production, the mechanism(s) underlying tPA release is unknown. METHODS AND RESULTS: We measured the effects of intra-arterial bradykinin (100, 200, and 400 ng/min), acetylcholine (15, 30, and 60 microg/min), and nitroprusside (0.8, 1.6, and 3.2 microg/min) on forearm vasodilation and tPA release in healthy volunteers in the presence and absence of (1) the B(2) receptor antagonist HOE 140 (100 microg/kg IV), (2) the NO synthase inhibitor L-N:(G)-monomethyl-L-arginine (L-NMMA, 4 micromol/min intra-arterially), and (3) the cyclooxygenase inhibitor indomethacin (50 mg PO TID). B(2) receptor antagonism attenuated vasodilator (P:=0.004) and tPA (P:=0.043) responses to bradykinin, without attenuating the vasodilator response to nitroprusside (P:=0.36). L-NMMA decreased basal forearm blood flow (from 2.35+/-0.31 to 1. 73+/-0.22 mL/min per 100 mL, P:=0.01) and blunted the vasodilator response to acetylcholine (P:=0.013) and bradykinin (P:=0.07, P:=0. 038 for forearm vascular resistance) but not that to nitroprusside (P:=0.47). However, there was no effect of L-NMMA on basal (P:=0.7) or bradykinin-stimulated tPA release (P:=0.45). Indomethacin decreased urinary excretion of the prostacyclin metabolite 2, 3-dinor-6-keto-prostaglandin F(1alpha) (P:=0.04). The vasodilator response to endothelium-dependent (P:=0.019 for bradykinin) and endothelium-independent (P:=0.019) vasodilators was enhanced during indomethacin administration. In contrast, there was no effect of indomethacin alone (P:=0.99) or indomethacin plus L-NMMA (P:=0.36) on bradykinin-stimulated tPA release. CONCLUSIONS: These data indicate that bradykinin stimulates tPA release from human endothelium through a B(2) receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway. Bradykinin-stimulated tPA release may represent a marker for the endothelial effects of endothelium-derived hyperpolarizing factor. (+info)
Investigation of chronic venous insufficiency: A consensus statement (France, March 5-9, 1997).
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This consensus document provides an up-to-date account of the various methods available for the investigation of chronic venous insufficiency of the lower limbs (CVI), with an outline of their history, usefulness, and limitations. CVI is characterized by symptoms or signs produced by venous hypertension as a result of structural or functional abnormalities of veins. The most frequent causes of CVI are primary abnormalities of the venous wall and the valves and secondary changes due to previous venous thrombosis that can lead to reflux, obstruction, or both. Because the history and clinical examination will not always indicate the nature and extent of the underlying abnormality (anatomic extent, pathology, and cause), a number of diagnostic investigations have been developed that can elucidate whether there is calf muscle pump dysfunction and determine the anatomic extent and severity of obstruction or reflux. The difficulty in deciding which investigations to use and how to interpret the results has stimulated the development of this consensus document. The aim of this document was to provide an account of these tests, with an outline of their usefulness and limitations and indications of which patients should be subjected to the tests and when and of what clinical decisions can be made. This document was written primarily for the clinician who would like to learn the latest approaches to the investigation of patients with CVI and the new applications that have emerged from recent research, as well as for the novice who is embarking on venous research. Care has been taken to indicate which methods have entered the clinical arena and which are mainly used for research. The foundation for this consensus document was laid by the faculty at a meeting held under the auspices of the American Venous Forum, the Cardiovascular Disease Educational and Research Trust, the European Society of Vascular Surgery, the International Angiology Scientific Activity Congress Organization, the International Union of Angiology, and the Union Internationale de Phlebologie at the Abbaye des Vaux de Cernay, France, on March 5 to 9, 1997. Subsequent input by co-opted faculty members and revisions in 1998 and 1999 have ensured a document that provides an up-to-date account of the various methods available for the investigation of CVI. (+info)