The venodilation effects of tapping versus massaging for venipuncture.

AIM: To compare the effectiveness of tapping and massaging venodilation techniques by evaluating venous cross-sectional area, venous depth, venous palpation score, and questionnaire responses of study participants. METHODS: This study had a quasi-experimental design. Between August 2016 and October 2016, healthy adult volunteers (n = 30, mean ± standard deviation of age: 22.3 ± 2.2 years) were enrolled in this study. Three venodilation techniques were evaluated: the application of a tourniquet (Control Group), the application of a tourniquet and tapping of the participant's forearm (Tapping Group), and the application of a tourniquet and massaging of the participant's forearm (Massage Group). RESULTS: In all three groups, venous cross-sectional areas increased significantly after the application of the venodilation technique. The change ratio of venous cross-sectional area was significantly larger in the Massage Group than in the Control Group. Additionally, 83.3% of the participants selected massaging as their preferred venodilation technique, stating the technique was comfortable and provided a feeling of relief. CONCLUSIONS: No significant differences were observed between the degrees of venodilation that were achieved using the three investigated venodilation techniques. Nonetheless, massaging was deemed the most effective technique after considering the participants' subjective comments.

Effects of transcutaneous electrical nerve stimulation via peroneal nerve or soleus muscle on venous flow: A randomized cross-over study in healthy subjects.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is used to prevent venous stasis and thromboembolism. However, best electrostimulation parameters have yet to be established. The aim of the study was to compare the hemodynamic effects and the participants' relative discomfort of 3 TENS sequences at the maximum tolerated intensity stimulus. METHODS: Twenty-four healthy university students (50% male) participated in a cross-over, randomized study. Each participant received 2 TENS sequences on peroneal nerve at 1 and 5 Hz, and the third one on soleus muscle at 5 Hz. Popliteal flow volume (FV) and peak velocity (PV) were measured using Doppler ultrasound and the relative change from basal values was recorded. Discomfort questionnaires -visual analogue scale (VAS) and verbal rating scale (VRS)- were also administered to compare sensations among the three applications. RESULTS: All interventions produced significant hemodynamic responses compared to baseline. Both 5 Hz applications obtained higher FV increments than 1 Hz TENS (P < .001). The muscle application resulted in the lowest PV increment (P < .001). TENS at 5 Hz on nerve location was the worst tolerated, with higher values in VRS (P = .056) and VAS (P = .11), although not significant. CONCLUSION: TENS at 5 Hz on soleus site may be the most appropriate protocol for enhancing venous return.

Measurement of blood flow in the deep veins of the lower limb using the geko™ neuromuscular electro-stimulation device.

BACKGROUND: A previous study using electrical stimulation of the common peroneal nerve (geko™) to activate the venous muscle pump measured blood flow in both the femoral and popliteal veins. Increased blood flow by as much as 60% was demonstrated in the femoral vein. Such an increase is assumed to be as a result of an increase in venous flow from the deep calf veins; however this has yet to be confirmed. The aim of this study was to conduct direct measurements in these deep calf veins to confirm this assumption in healthy individuals. METHODS: This was a single centre open-label intra-subject healthy volunteer comparison of blood flow in the peroneal, posterior tibial and gastrocnemial veins with and without the geko™ device. The device was applied to 18 volunteers. Peak venous velocity (PV) and ejected volume per individual stimulus (VS) and volume flow (VF) was determined using ultrasound. RESULTS: Peak velocity (PV) increased 216% in the peroneal vein, by 112% in the posterior tibial vein and by 137% in the gastrocnemial vein (P<0.001). Ejected volume per stimulus increased by 113% in the peroneal vein, by 38% in the posterior tibial vein and by 50% in the gastrocnemial vein (P<0.003). Associated volume flows during the muscle contraction were increased by 36%, 25% and 17%, respectively (P=0.05) CONCLUSIONS: This is the first time that neuromuscular electro-stimulation has been shown to be an effective method of increasing flow in the axial deep veins of the calf. Significant increases in velocity and volume flow in response to the electrical stimulus were seen in all three veins studied. Enhancements of both blood velocity and volume flow are key factors in the prevention of venous stasis and ultimately deep vein thrombosis (DVT). Further studies are justified to determine the efficacy of the device in the prevention of DVT.

Tapping but not massage enhances vasodilation and improves venous palpation of cutaneous veins.

This paper investigated whether tapping on the median cubital vein or massaging the forearm was more effective in obtaining better venous palpation for venipuncture. Forty healthy volunteers in their twenties were subjected to tapping (10 times in 5 sec) or massage (10 strokes in 20 sec from the wrist to the cubital fossa) under tourniquet inflation on the upper arm. Venous palpation was assessed using the venous palpation score (0-6, with 0 being impalpable). Three venous factors-venous depth, cross-sectional area, and elevation-were also measured using ultrasonography. The venous palpation score increased significantly by tapping but not by massage. Moreover, all 3 venous measurements changed significantly by tapping, while only the depth decreased significantly by massage. The three venous measurements correlated significantly with the venous palpation score, indicating that they are useful objective indicators for evaluating vasodilation. We suggest that tapping is an effective vasodilation technique.

Aplexone targets the HMG-CoA reductase pathway and differentially regulates arteriovenous angiogenesis.

Arterial and venous endothelial cells exhibit distinct molecular characteristics at early developmental stages. These lineage-specific molecular programs are instructive to the development of distinct vascular architectures and physiological conditions of arteries and veins, but their roles in angiogenesis remain unexplored. Here, we show that the caudal vein plexus in zebrafish forms by endothelial cell sprouting, migration and anastomosis, providing a venous-specific angiogenesis model. Using this model, we have identified a novel compound, aplexone, which effectively suppresses venous, but not arterial, angiogenesis. Multiple lines of evidence indicate that aplexone differentially regulates arteriovenous angiogenesis by targeting the HMG-CoA reductase (HMGCR) pathway. Treatment with aplexone affects the transcription of enzymes in the HMGCR pathway and reduces cellular cholesterol levels. Injecting mevalonate, a metabolic product of HMGCR, reverses the inhibitory effect of aplexone on venous angiogenesis. In addition, aplexone treatment inhibits protein prenylation and blocking the activity of geranylgeranyl transferase induces a venous angiogenesis phenotype resembling that observed in aplexone-treated embryos. Furthermore, endothelial cells of venous origin have higher levels of proteins requiring geranylgeranylation than arterial endothelial cells and inhibiting the activity of Rac or Rho kinase effectively reduces the migration of venous, but not arterial, endothelial cells. Taken together, our findings indicate that angiogenesis is differentially regulated by the HMGCR pathway via an arteriovenous-dependent requirement for protein prenylation in zebrafish and human endothelial cells.

Left ventricular mechanical activity detected by impedance recording.

AIMS: Recording and analysing impedance fluctuation along the cardiac cycle in the right (RV) and left ventricles (LV). METHODS AND RESULTS: During a biventricular (BiV) implantation procedure, impedance was sequentially derived between the atrial ring electrode and either electrode (tip or ring) of the RV lead [transvalvular impedance (TVI)], and between the atrial ring and either the tip or ring electrode of a coronary sinus lead, positioned in a cardiac vein [left ventricle impedance (LVI)]. The LVI signal was also recorded by the implanted pacemaker at the 1 day and 3 months follow-ups. With intrinsic conduction, TVI showed an average increase of 53 +/- 29 ohm during ventricular systole, whereas at the same time, LVI decreased by 45 +/- 21 ohm (25 and 23 patients, respectively, out of 28 tested cases). Transvalvular impedance and LVI displayed a similar time course, which appeared to be related to the systolic timing in the RV and LV. Both LVI amplitude and duration decreased as a function of the cardiac rate. The LVI deflection started immediately after LV stimulation, and often anticipated the R-wave sensing after contralateral pacing. At the 3-month follow-up, LVI amplitude was decreased in 70% of cases and increased in the remainder, with a non-significant average change of -5 +/- 85% with respect to the acute recordings. CONCLUSION: Transvalvular impedance properties are consistent with the assumption of an inverse relationship with RV volume. Though LVI requires a different physical interpretation, the waveform duration might reflect the timing of LV myocardial contraction. In this hypothesis, the relationship between TVI and LVI could provide insight into the effects of BiV pacing on mechanical synchronization.

Erectile function restoration after repair of excised cavernous nerves by autologous vein graft in rats.

INTRODUCTION: Cavernous nerves (CNs) injury is the main cause of erectile dysfunction (ED) following radical prostatectomy. Its restoration remains challenging. AIM: To investigate the feasibility of erectile function recovery by autologous vein graft after bilateral CNs being excised in a rat model. METHODS: A total of 36 adult male Sprague-Dawley rats were randomized into three groups. A 5mm segment of CN was excised bilaterally in group B and C. In group B, a 7-mm segment of autologous saphenous vein was interposed at the defect site bilaterally, with two nerve stumps inserted into the vein lumen. Group C underwent no repair. Group A was accepted a sham operation. 4 months later, apomorphine tests were performed on each rat, followed by injection of 4% fluorogold into bilateral corpus cavernous. 5 days later, after monitoring intracorporal pressure (ICP) changes induced by electrostimulation of CN, rats were sacrificed and their bilateral major pelvic ganglions were obtained for detection of fluorogold, and penile tissues of middle shaft were obtained for detecting nitric oxide synthase-containing nerve fibers in penile dorsal nerves. MAIN OUTCOME MEASURES: Erectile function was assessed by apomorphine test and ICP monitoring. CN regeneration was judged by fluoroglod tracing and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. RESULTS: Apomorphine tests resulted in 58% rats with erectile responses in group B, whereas no erection was observed in group C. ICP monitoring also demonstrated a significant recovery in erectile function in group B compared with group C. Much more and brighter fluorogold coloring cells were examined in major pelvic ganglions of group B than those of group C. NADPH-diaphorase staining also showed much more positive fibers were detected in penile dorsal nerves in group B than in group C. CONCLUSION: Autologous vein graft could provide a guide channel to induce CN regeneration and successfully restore autonomic erectile function after CNs being excised in rats.

Endovenous laser therapy--application studies and latest investigations.

Endovenous laser therapy (ELT) was introduced in clinical practice as a therapy for incompetent veins about ten years ago. One characteristic of ELT is the broad spectrum of different treatment protocols by means of a variety of laser systems as well as manifold application forms and dosimetry concepts are under investigations. Clinical results with effective, relatively pain-free occlusion of incompetent varicosis veins have been observed, as well as undesired side effects such as ecchymosis, phlebitis and recanalization. In recent years systematic experimental investigations and the analysis of clinical results have increased the understanding of the interrelation between the clinical and physical aspects, followed to a continuous optimization of ELT. The use of IR wavelengths and radial irradiation concepts, together with continuous moving of the optical fiber seem to reduce possible side effects. This way ELT treatment becomes a more standardized effective method for the treatment of varicose veins. In future controlled randomized studies are required to compare optimized ELT treatment with other endoluminal modalities as well as conventional surgery.

Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black walnut heartwood extract induced equine laminitis.

Inflammation and vascular dysfunction occur concurrently during the prodromal stages of equine laminitis. The aim of this study was to provide insights into the role that thromboxane and isoprostanes may play in the development of black walnut heartwood extract (BWHE)-induced laminitis. Horses were divided into two groups, either control or BWHE-administered horses. Plasma concentrations of thromboxane increased transiently after administration of BWHE and coincided with the nadir in white blood cell counts, whereas plasma concentrations of iso-prostaglandin PGF(2alpha) (iso-PGF(2alpha)) did not change in either group. At 12h (for the control group) or Obel grade 1 laminitis (for the BWHE group) the horses were euthanized and laminar tissue collected. Laminar arteries and veins were used in functional studies with vasoconstrictor substances and tissue samples were used for the determination of laminar iso-PGF(2alpha) concentrations. Laminar tissue concentrations of iso-PGF(2alpha) were significantly greater in BWHE horses when compared to control horses. In parallel studies concentrations of iso-PGF(2alpha) in laminar tissue samples obtained 1.5 and 3h after administration of BWHE were indistinguishable from those for control horses at 3 or 12h after administration of an equal volume of water. Laminar vessel constrictor responses to either a thromboxane mimetic (U46619), iso-prostaglandin PGE(2) (iso-PGE(2)) or iso-PGF(2alpha) were determined using small vessel myographs. In some vessels, the effects of putative prostanoid and thromboxane receptor antagonists, SQ 29,548, SC-19220 and AH 6809, upon contractile responses were determined. In control horses, U46619, iso-PGF(2alpha) and iso-PGE(2) more potently and efficaciously constricted laminar veins when compared to laminar arteries. Responses of laminar veins from BWHE horses to iso-PGE(2) were similar to those of laminar veins from control horses, whereas iso-PGF(2alpha) elicited significantly greater responses in laminar veins from BWHE horses when compared to controls. In contrast, responses to U46619 were smaller in laminar veins isolated from BWHE horses when compared to those in laminar veins from control horses. In the presence of SQ 29,548, iso-PGF(2alpha) elicited a small dilation in laminar veins from control horses, which was not apparent in laminar veins from BWHE horses. These results are consistent with both systemic and local inflammatory events occurring during the prodromal stages of BWHE-induced laminitis. Because laminar veins are sensitive to thromboxane and isoprostanes, these substances may act as conduits between the inflammatory and vascular events occurring in laminitis and may be therapeutic targets for this crippling condition.

A haemodynamic study of the physiological mechanisms of the venous pump in the healthy human foot.

Presented is a physiological study of the plantar venous plexus in the context of venous return. It is accepted that the plantar venous plexus acts as a peripheral venous pump, capable of emptying blood from the foot into the posterior tibial veins. Controversy still exists, however, over the precise physiological mechanism which is responsible for completely emptying the deep plantar veins of the foot. This study was designed to investigate whether weight bearing or muscular contraction was the dominant mechanism involved. This was achieved by comparing blood flow measurements taken from the posterior tibial and popliteal veins while performing specific foot exercises. Measurements were taken using Doppler ultrasound. Neuromuscular electrical stimulation was also used to study the blood flow obtained by artificially inducing contraction of the plantar venous plexus.

Relaxation of human placental arteries and veins by ATP-sensitive potassium channel openers.

BACKGROUND: Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)) are important modulators of vascular tone. Preliminary data from our laboratory suggests that K(ATP) channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific K(ATP) opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative K(ATP) channel openers. MATERIALS AND METHODS: Functional activity of K(ATP) channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced relaxations were assessed in the presence and absence of agonist-induced pretone. Cromakalim, an established K(ATP) channel opener, acted as control. RESULTS: KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitors of the nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation. CONCLUSIONS: We conclude that K(ATP) channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of K(ATP) channels and via activation of nitric oxide-dependent pathways.

Difference in rates of net portal absorption between crystalline and protein-bound lysine and threonine in growing pigs fed once daily.

Net portal absorption of AA during the 6-h postprandial period was measured in eight gilts (48.5 +/- 1.6 kg BW) in a crossover design. The pigs had chronic catheters placed in the portal vein, carotid artery, and ileal vein, and were trained to consume 1.2 kg of a standard grower diet once daily. Blood samples were taken every 30 min for 4 h and then hourly until 6 h after feeding. The first set of blood samples was taken after pigs were fed a meal of the test 16% CP corn-soybean meal diet (16% CP) or the test 12% CP corn-soybean meal diet supplemented with crystalline lysine, threonine, and tryptophan (12% CP + AA) to equal the three AA levels in the 16% CP diet. Pigs were then fed the standard diet for 2 d. Following that, blood samples were again taken after the pigs were fed a meal of the test diet that was not given to them at the first sampling period. Net portal AA absorption was calculated by multiplying porto-arterial plasma AA concentration difference by portal vein plasma flow rate (PVPF), estimated by an indicator-dilution technique employing p-aminohippuric acid as the indicator infused into the ileal vein. Plasma concentrations of lysine and threonine of pigs were affected by the diet x time interaction (P < 0.01). Portal and arterial plasma lysine and threonine concentrations in pigs attained the maximal level by 1 h postprandial when the 12% CP + AA diet was fed, but reached the peak level at 2.5 h postprandial when the 16% CP diet was given. The PVPF of pigs over the 6 h postprandial was less (P < 0.01) when the 12% CP + AA diet was given than when the 16% CP diet was fed. Net portal absorptions of lysine and threonine also were affected (P < 0.05) by time x diet interaction. The peak portal absorption of both lysine and threonine in pigs appeared at 0.5 h postprandial when the 12% CP + AA diet was given, but at 2.5 h postprandial with the feeding of the 16% CP diet. The early appearance of peak portal absorption of lysine and threonine from feeding the 12% CP + AA compared with the 16% CP diet indicates that crystalline lysine and threonine are absorbed more rapidly than protein-bound lysine and threonine in pigs fed once daily.

Conduction patterns in the cardiac veins: electrophysiologic characteristics of the connections between left atrial and coronary sinus musculature.

INTRODUCTION: Fractionated electrograms and double potentials have been well described within the coronary sinus (CS) in humans. The pattern of circumferential activation in the CS has not been investigated. Furthermore, no data exist on conduction characteristics within the great cardiac vein (GCV) or the middle cardiac vein (MCV). METHODS AND RESULTS: Twenty patients underwent catheter mapping of the CS, the MCV, and the GCV. Anatomical areas were verified by cannulation of the left superior pulmonary vein. The pattern of circumferential muscle activation within the proximal CS was also studied with a circular mapping catheter (Lasso 12 mm). At conventional mapping during sinus rhythm and high right atrial pacing, discrete double potentials or fractionated electrograms were recorded during left, right atrial and CS pacing at the CS ostium, mid-CS, and distal CS-ligament of Marshall area, in 2 (10%), 1 (5%), and 9 (45%) patients, respectively, whereas no patient displayed such signals in the MCV or GCV ( p < 0.001). Proximal CS mapping with the Lasso was accomplished in 10 patients, 7 of whom had no evidence of multicomponent potentials in the CS at conventional mapping. Specific CS potentials dissociated from the atrial electrograms were recorded in all patiens with the use of circumferential mapping. The perimetric distribution of electrograms within the CS suggested an oblique course of conduction across the CS musculature. CONCLUSION: Potentials representing activation of the CS musculature, with an oblique course of conduction across the CS, can be recorded in human CS but not in the GCV or MCV. This is compatible with anatomical observations of sinus venosus musculature covering the CS but not other cardiac veins, and supports the rationale for the role of CS musculature in the generation of atrial arrhythmias.

Effect of folic acid on nitrate tolerance in healthy volunteers: differences between arterial and venous circulation.

This study investigated whether oral supplemental folic acid can prevent the development of nitrate tolerance and whether it has different effects on the arterial and venous systems. Twenty-four healthy male volunteers received either placebo or folic acid (10 mg/d) for 14 days. Additionally, all subjects underwent concurrent transdermal nitroglycerin therapy for 7 days. Venous occlusion forearm strain gauge plethysmography measured arterial and venous responses to sublingual nitroglycerin before and after treatment. Both arterial and venous responses were blunted in the placebo group after transdermal nitroglycerin. Folic acid prevented the development of nitrate tolerance in arteries but had no effect in veins.

The use of lipid emulsions for the i.v. administration of a new water soluble polyene antibiotic, SPK-843.

Venous tolerance of a new water soluble polyene antibiotic, SPK-843, in 5% glucose solution for infusion is low in laboratory animals. The use of Intralipid 10% emulsion was therefore proposed, in which the antibiotic remained chemically stable for at least 2 h in a mildly acid or nearly neutral environment and at concentrations of 0.1-0.5 mg/mL, producing no alterations in the emulsion structure. Tolerance was assessed through repeated infusions in the ear marginal vein of rabbits and was found much more satisfactory than the tolerance observed when the vehicle used was 5% glucose solution. The study of the effect of some variables (concentration, volume infused, dose per kg) on venous toxicity offered the possibility to plan optimal administration conditions of presumed therapeutic doses.

[Comparative efficiency of correction of unfavorable effects of hypokinesia by compression of veins of lower extremities and local thermovasodilatation]. / Sravnitel'naia otsenka éffektivnosti korrektsii neblagopriiatnykh éffektov gipokinezii metodami kompressii ven nizhnikh konechnostei i lokal'noi termovazodilatatsii.

As a result of the trials it was established that occlusion of the veins in the lower limbs made by means of "Pneumatic" suit under the pressure 60 mmHg in the cuffs is as effective as local thermovasodilation in the area of feet, crura and thighs with submaximal intensity in terms of protective redistribution of blood in experimental hypokinesia. These methods can be used for correction of negative symptoms of hypokinesia. Occlusion of the veins is less effective than local thermotherapy in normalization of subjective assessment of general condition, activity, mood and reactive-situational anxiety.

Vascular gene discovery using laser capture microdissection of human blood vessels and quantitative PCR.

Recent approaches to candidate gene identification and cellular localization have included RNA derived from complex whole tissue profiling on cDNA microarrays followed by in situ hybridization with riboprobes. In this study, the Arcturus PixCell II laser capture microdissection (LCM) system, an argon-based laser-assisted method for the isolation of specific cell types from heterogeneous tissue samples, was used to microdissect the tunica media from normal human arteries and veins (n = 5 in each group). Total RNA was extracted from the sum of 10,000 shots for each blood vessel using the Strataprep MicroKit. RNA was reverse-transcribed, and the resulting cDNA was analyzed using the Applied Biosystems 7700 quantitative PCR system (Q-PCR). Control genes, such as the L-type calcium channel, PECAM (CD-31), and beta-2 microglobulin, were used to assess sample quality and purity. Of 10 laser-captured media samples, five (50%) showed a gene profile that indicated high-quality RNA (abundance of housekeeping genes) and smooth muscle cell enrichment (low levels of PECAM and high levels of the L-type calcium channel). We conclude that the application of the LCM technique to collect smooth muscle cell RNA from the tunica media of human blood vessels can assist in the validation of gene expression and potentially expedite the identification of novel, regulated genes present within vascular smooth muscle.

[Effect of various modes of electric stimulation of lower extremity skeletal muscles on indicators of peripheral blood flow]. / Vliianie razlichnykh rezhimov élektrostimuliatsii skeletnykh myshts nizhnikh konechnostei na pokazateli perificheskogo krovotoka.

Various modes of electrostimulation of the musculus gastrocnemius (MG) were examined for effect on doppler parameters of blood flow in the popliteal artery and vein of 15 healthy subjects at the age 30.6 +/- 1.5 years. The strongest effect on the circulation in the popliteal artery was observed at the stimulation with 16-second stimulus alternating with 16-second pause. Such mode led to dilation of the artery diameter by 16.2%, maximal blood flow speed increased by 50.6%, time-averaged circulation was by 60.4% faster. Electrostimulation of the crural muscles also induced dilation of the popliteal vein and accelerated relevant circulation. These changes were also most evident in the stimulation mode 16-second stimulation intermittent with a pause.

A flexible algorithm for construction of 3-D vessel networks for use in thermal modeling.

A new algorithm for the construction of artificial blood vessel networks is presented. The algorithm produces three-dimensional (3-D) geometrical representations of both arterial and venous networks. The key ingredient of the algorithm is a 3-D potential function defined in the tissue volume. This potential function controls the paths by which points are connected to existing vessels, thereby producing new vessel segments. The potential function has no physiological interpretation, but, by adjustment of parameters governing the potential, it is possible to produce networks that have physiologically meaningful geometrical properties. If desired, the veins can be generated counter current to the arteries. Furthermore, the potential function allows fashioning of the networks to the presence of bone or air cavities. The resulting networks can be used for thermal simulations of hyperthermia treatment.

Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo.

BACKGROUND: Endothelial dysfunction occurs in many diseases associated with increased cardiovascular risk. We examined the effects of pro-inflammatory cytokines on endothelial function. METHODS AND RESULTS: Subjects lay with one hand placed on an angled support. The diameter of a vein was recorded by measuring the linear displacement of a probe placed on the skin overlying the vein when the pressure in a congesting cuff placed around the upper arm was deflated from 40 to 0 mm Hg. A length of the vein was isolated by two wedges. TNF-alpha (1 ng), IL-1beta (1 ng), or IL-6 (100 pg) were instilled for 1 hour, either individually or together. At the end of the hour, the wedges were removed and the vein reconnected with the circulation. Dose-response curves (bradykinin: 2, 4, and 8 pmol/min; arachidonic acid: 0.2, 2, and 20 nmol/min; and glyceryl trinitrate 1, 2, and 4 pmol/min) were constructed before and 1, 6, 24, and 48 hours after instillation. In another study, hydrocortisone (100 mg) was given 2 hours before the study. In a different study, subjects were given oral aspirin (75 mg or 1 g) 2 hours before the study. TNF-alpha and IL-1beta alone but not IL-6 attenuated the dilatation to bradykinin and arachidonic acid; the response was greatest at 1 hour with recovery occurring by 6 hours. Combination of IL-1beta and TNF-alpha prolonged the endothelial dysfunction, resulting in recovery at 24 hours. Hydrocortisone and high-dose aspirin prevented endothelial dysfunction. CONCLUSIONS: The results demonstrate that pro-inflammatory cytokines induce transient and reversible endothelial dysfunction and indicate that cyclooxygenase activity may contribute to the genesis of the effect. If other vessels behave similarly, this may provide further insight into the mechanisms precipitating acute cardiovascular events after inflammatory disorders.