Biomedical subjects

M Schmitt

Publications and source records attributed to M Schmitt.

At least 55 records · Page 3Linked to original sources

PubMed2003

TRAIL-beta and TRAIL-gamma: two novel splice variants of the human TNF-related apoptosis-inducing ligand (TRAIL) without apoptotic potential.

Tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a recently identified member of the TNF family, which induces programmed cell death in a variety of neoplastic cell types, but not in most nonneoplastic cells. In this study, we report on the identification of two novel alternative splice variants of TRAIL in neoplastic and non-neoplastic human cells lacking either exon 3 (TRAIL-beta) or exons 2 and 3 (TRAIL-gamma). In both splice variants, loss of exon 3 resulted in a frame shift generating a stop codon with consecutive extensive truncation in the extracellular domain. Ectopic expression revealed a loss of proapoptotic potential for both alternative splice variants. In contrast to the predominantly cytoplasmatic localisation of GFP-tagged TRAIL-alpha and TRAIL-beta, TRAIL-gamma showed an additional association with the cell surface and nuclear membrane. In conclusion, alternative splicing might be involved in fine tuning of TRAIL-induced apoptosis and underlines the complexity of the TRAIL system.

Alternative Splicing↗

PubMed2003

Predialing the number of cinegraphic frames enables an effective patient dose due to coronary angiography of 0.8 mSv.

PURPOSE: To investigate the effect of a new device for predialing the number of cinegraphic frames before each coronary angiogaphy, with the objective of reducing the patient dose area product (DAP) from coronary angiography, which typically requires 1000 to 2350 cinegraphic frames. That DAP is high and stated to be between 15.6 to 106.3 Gy x cm (2). Applying the accepted DAP-to-ED conversion factors, for the thoracic region of approximately 0.20 mSv/Gy x cm (2), this corresponds to a mean effective dose (ED) in the range of 3.1 to 21.3 mSv. MATERIAL AND METHODS: For patients undergoing elective coronary angiography, we compared various parameters of radiation exposure obtained with judicious radiation reducing standard techniques (n = 106) and with an additional new rotary switch for predialing the number of cinegraphic frames (n = 106). RESULTS: The patient radiation dose was significantly lower with the new device, with the mean DAP reduced to 5.5 from 9.1 Gy x cm (2). The corresponding reducation of the mean DAP for left ventriculography and coronary angiography was 1.3 from 1.7, and 4.2 from 7.4 Gy x cm (2), respectively. The number of cinegraphic frames was 98 vs. 184, whereas the number of cinegraphic runs and the fluoroscopy time were comparable. CONCLUSION: Predialing the cinegraphic frame number before each cinegraphic run enables a reduction of the patients effective dose from coronary angiography to 0.8 mSv, i. e. to 57 % of the baseline value and far below typically reported values.

Aged↗

PubMed2003

Late improvement of regional wall motion after the subacute phase of myocardial infarction treated by acute PTCA in a 6-month follow-up.

BACKGROUND: The aim of this follow-up study was to investigate the late effects of acute coronary angioplasty (PTCA) on regional wall motion after the subacute phase of myocardial infarction (MI). METHODS AND RESULTS: Seventeen patients were investigated initially at a median of 11 days and again at 6 months after acute PTCA for myocardial infarction (< 8 hours after onset of symptoms) by cardiac magnetic resonance imaging. Corresponding short-axis slices encompassing the left ventricle (LV) were acquired using a standard cine MR for regional wall motion analysis and using delayed contrast enhanced magnetic resonance imaging (ceMRI) for infarct size quantification. The infarct size was similar in the subacute phase and the 6 month follow-up (20.8 and 21.9%, respectively; n.s.). Regional wall motion improved significantly in the area of hyperenhancement [percentage wall thickening (PWT) 21.9% and 37.9%, p < 0.05] in contrast to remote normal myocardium (46.4% and 38.4%; n.s.). Regional wall motion was significantly poorer in transmural compared with nontransmural MI in the subacute stage, and a late improvement could only be observed in transmural MI. CONCLUSION: Transmural areas of hyperenhancement displayed significant late long-term improvement of regional wall motion after acute PTCA, possibly related to prolonged stunning compared with nontransmural areas.

Adult↗

PubMed2003

Radiation exposure benefit of a lead cap in invasive cardiology.

BACKGROUND: Occupational head exposure to radiation in cardiologists may cause radiation induced cataracts and an increased risk of brain cancer. OBJECTIVE: To determine the effectiveness of 0.5 mm lead equivalent caps, not previously used in invasive cardiology, in comparison with a 1.0 mm lead equivalent ceiling mounted lead glass screen. DESIGN: An anthropomorphic Alderson-Rando phantom was used to represent the patient. Scatter entrance skin air kerma to the operator position (S-ESAK-O) was measured during fluoroscopy for all standard angulations and the S-ESAK-O per dose-area product (DAP) calculated, as applied to the phantom. RESULTS: Measured mean (SD) left/right anterior oblique angulation ratios of S-ESAK-O without lead devices were 23.1 (10.1), and varied as a function of tube angulation, body height, and angle of incidence. S-ESAK-O/DAP decreased with incremental operator body height by 10 (3)% per 10 cm. A 1.0 mm lead glass shield reduced mean S-ESAK-O/DAP originating from coronary angiography from 1089 (764) to 54 (29) nSv/Gy x cm2. A 0.5 mm lead cap was effective in lowering measured levels to 1.8 (1.1) nSv/Gy x cm2. Both devices together enabled attenuation to 0.5 (0.1) nSv/Gy x cm2. The most advantageous line of vision for protection of the operator's eyes was > or = 60 degrees rightward. CONCLUSIONS: Use of 0.5 mm lead caps proved highly effective, attenuating S-ESAK-O to 2.7 (2.0) x 10(-3) of baseline, and to 1.2 (1.4) x 10(-3) of baseline where there was an additional 1.0 mm lead glass shield. These results could vary according to the x ray systems used, catheterisation protocols, and correct use of radiation protection devices.

Cardiology↗

PubMed2003

Is a combination of Tc-SPECT or perfusion weighted magnetic resonance imaging with spinal tap test helpful in the diagnosis of normal pressure hydrocephalus?

OBJECTIVE: The aim of this study was to evaluate the combination of spinal tap test (STT) with cerebral perfusion measurement assessed either by Tc-bicisate-SPECT (Tc-SPECT) or perfusion weighted MRI (pwMRI), or both, for a better preoperative selection of promising candidates for shunt operations in suspected idiopathic normal pressure hydrocephalus. METHODS: 27 consecutive patients were examined with a standard clinical protocol (assessed by the Homburg Hydrocephalus Scale (HHS)) as well as with 99m Tc-bicisate-SPECT (n=27) or additionally by pwMRI (n=12) before and after STT. The results of these examinations were compared preoperatively for each patient and correlated with postoperative clinical outcome after shunt surgery. RESULTS: Nine patients showed both, a clinical improvement, and increased cerebral perfusion after STT. They underwent shunt surgery with good to excellent results. In another nine patients increasing cerebral perfusion was detected although they did not show a clear clinical improvement after STT. Six of them also received a shunt operation with good to excellent outcome. Three patients of the last group could have an operation. Nine patients did not show any clinical improvement or any kind of increasing cerebral perfusion after STT. Therefore, they did not undergo surgery. The results of SPECT and pwMRI correlated in 92 % of the patients (11 of 12). CONCLUSION: It is concluded that a combination of clinical assessment with SPECT or pwMRI is helpful in the preoperative selection of patients for shunting procedures with suspected NPH syndrome. This combination is a minimal invasive and objective test modality that is superior to STT alone. Further studies are necessary for a comparison of the described imaging techniques with different diagnostic tests in this difficult field of cerebral disease.

Adult↗

PubMed2003

Short communication: time of day influences patient radiation exposure from percutaneous cardiac interventions.

The objective of this study was to investigate the influence of time of day on patient radiation exposure due to cardiac interventions. The elective interventional workload of one experienced cardiologist documented over the course of 4 months amounted to 325 diagnostic catheterizations and 145 percutaneous coronary interventions (PCI). All radiation parameters documented during diagnostic coronary angiography remained constant throughout the entire day. In contrast, for PCI measurements made from 7:00 a.m. to 1:00 p.m., our study revealed a mean overall dose-area product (DAP) of 11.8+/-6.8 Gy cm(2) (n=115). These radiation exposure levels increased significantly later in the afternoon (n=30) by 28% to a level of 15.0+/-11.1 Gy cm(2) (p<0.045). Cinegraphic DAP increased from 3.7+/-2.7 Gy cm(2) to 5.0+/-3.2 Gy cm(2) (p<0.033). The number of cinegraphic runs and frames rose from 7.9+/-2.9 to 9.1+/-3.1 (p<0.025), and from 136+/-63 to 164+/-70 (p<0.014), respectively. The following conclusion is warranted by our data and should now be confirmed in a wider multicentre study: radiation protection of the patients could be influenced by the fatigue of the cardiologist conducting the procedure. To enhance patient radiation safety, elective percutaneous angioplasty should be scheduled for the first 6 h of the interventionalist's occupational workload. Diagnostic interventions may be safely scheduled later.

Angioplasty, Balloon, Coronary↗

PubMed2002

Initiation of HAART in drug-naive HIV type 1 patients prevents viral breakthrough for a median period of 35.5 months in 60% of the patients.

The introduction of potent combinations of antiviral drugs is a major breakthrough in the treatment of HIV. We investigated the long-term virologic outcome and the development of resistance after initiating highly active antiretroviral therapy (HAART) in drug-naive patients in daily clinical practice. Twenty-five treatment-naive HIV-1 patients were started on HAART. Fifteen patients responded with a drop in viral load below the limit of detection during 35.5 (interquartile range: 7) months of therapy. In 6 of 10 patients with virologic failure, virus with resistance-related mutations against the received drugs emerged. Compared with responders (R), nonresponding (NR) patients were in a later disease stage at therapy start (p = 0.0089) with lower CD4 cell counts at baseline (p = 0.040), and a lower proportion of nonresponders showed protease inhibitor (PI) levels above C(min) (p = 0.049). More NR patients showed secondary PI mutations at baseline (p = 0.079), and the CCR2-64I coreceptor polymorphism was absent among NR patients, compared with 38.5% of R patients displaying CCR2-64I (p = 0.053), although the differences were not significant. In conclusion, starting HAART in antiretroviral drug-naive HIV-infected patients followed in daily clinical practice prevented viral breakthrough for up to 44 months in 60% of the patients. Virologic failure was associated with the development of resistance-related mutations, a later stage of disease at start of therapy and lower PI drug levels.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Femtosecond coherent Raman spectroscopy and its application to porphyrins.

The results on femtosecond time-resolved coherent anti-Stokes Raman scattering (CARS) experiments for the analysis and control of ground state vibrational dynamics of porphyrin systems are briefly reviewed. By detecting the spectrum of the transient CARS signal, a detailed mapping of the dynamics initiated by the stimulated Raman pump process is achieved. The method yields the dephasing behavior and spectral information of the investigated system at the same time. The different contributions to the ground state vibrational dynamics are selected by changing the direction of the CARS signal analyzer in the polarization arrangement used.

Binding Sites↗

PubMed2002

Crystallization at the polymer/calcium-phosphate interface in a sterilized injectable bone substitute IBS.

Calcium phosphate (CaP) ceramics are the main raw materials used to elaborate blocks or granules for bone substitutes. In this study, injectable bone substitutes (IBS) were developed for applications in orthopedic or dental surgery. Sterile, ready-to-use composite containing CaP granules (biphasic calcium phosphate, BCP) and polymer (hydroxypropylmethylcellulose, HPMC) was prepared. Steam sterilization produced new phenomena at the CaP/polymer interface, resulting in crystal growth. These phenomena may constitute a model for the biomineralization study. Scanning electron microscopy showed that the formed crystallites organize themselves into a three-dimensional structure. Currently, the mechanisms of crystal growth are unknown and have been observed with only one combination of polymer/BCP ceramics after steam sterilization.

Biocompatible Materials↗

PubMed2002

Differential subcellular localization of functionally divergent survivin splice variants.

Survivin is an inhibitor of apoptosis protein (IAP) that is markedly overexpressed in most cancers. We identified two novel functionally divergent splice variants, i.e. non-antiapoptotic survivin-2B and antiapoptotic survivin-deltaEx3. Because survivin-2B might be a naturally occurring antagonist of antiapoptotic survivin variants, we analyzed the subcellular distribution of these proteins. PSORT II analysis predicted a preferential cytoplasmic localization of survivin and survivin-2B, but a preferential nuclear localization of survivin-deltaEx3. GFP-tagged survivin variants confirmed the predicted subcellular localization and additionally revealed a cell cycle-dependent nuclear accumulation of survivin-deltaEx3. Moreover, a bipartite nuclear localization signal found exclusively in survivin-deltaEx3 may support cytoplasmic clearance of survivin-deltaEx3. In contrast to the known association between survivin and microtubules or centromeres during mitosis, no corresponding co-localization became evident for survivin-deltaEx3 or survivin-2B. In conclusion, our study provided data on a differential subcellular localization of functionally divergent survivin variants, suggesting that survivin isoforms may perform different functions in distinct subcellular compartments and distinct phases of the cell cycle.

Alternative Splicing↗

PubMed2002

[Evaluation of myocardial perfusion reserve in patients with CAD using contrast-enhanced MRI: a comparison between semiquantitative and quantitative methods].

OBJECTIVE: Comparison between two semiquantitative methods and a quantitative evaluation of myocardial blood flow (MBF) for assessment of myocardial perfusion reserve (MPR) in patients with CAD. MATERIAL AND METHODS: 9 patients with coronary stenoses > 50 % were examined with an ECG-gated Saturation Recovery Turbo FLASH sequence by using Gd-DTPA as contrast agent (CA). The entive measurements were performed both during rest and hyperemia induced by adenosine. The up-slopes of the signal-time S(t) curves in the myocardium and left ventricular (LV) cavity were evaluated by a linear fit. MPR was calculated from the original up-slopes of the myocardial S(t) curves and from the up-slopes, which were normalized to the up-slopes of the LV S(t) curves, respectively. For quantification of MBF values, the mathematical model MMID 4 was used and MPR was evaluated from the MBF values. RESULTS: With all tested methods, MPR was reduced in myocardial regions subtended by arteries with stenoses >/= 70 % compared with remote regions. With MMID 4 and the normalized up-slope method, differences between severe ischemic and remote regions were statistically significant. CONCLUSION: The up-slope method with normalization and quantification with MMID 4 are more sensitive methods to differentiate between remote and ischemic myocardium than the up-slope method without normalization.

Adult↗

PubMed2002

Large cerebral vessel occlusive disease in Lyme neuroborreliosis.

We report on a 12-year-old, previously healthy girl with an acute hemiparesis as the predominant clinical manifestation of Lyme neuroborreliosis (LNB). The diagnosis of LNB was based on cerebrospinal fluid (CSF) studies, laboratory findings and the clinical course whereas the patient's history and the lack of characteristic skin lesions obscured the diagnosis in the beginning. After four weeks of antibiotic and physiotherapeutic treatment, the hemiparetic symptoms had completely resolved. Although evidence of vasculitic and perivascular inflammation in LNB has been described in the literature, large cerebral vessel occlusive disease represents a rare finding. Appropriate treatment strategies can lead to good clinical rehabilitation, as shown in this case, making the timely diagnosis a crucial issue. We conclude that LNB should be considered in every stroke-like episode of unknown origin in children, even in the absence of a history of a tick bite or typical skin lesions.

Arterial Occlusive Diseases↗

PubMed2002

Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist.

Ro 63-1908, 1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol, is a novel subtype-selective N-methyl-D-aspartate (NMDA) antagonist that has been characterized in vitro and in vivo. Ro 63-1908 inhibited [(3)H]dizocilpine ((3)H-MK-801) binding in a biphasic manner with IC(50) values of 0.002 and 97 microM for the high- and low-affinity sites, respectively. Ro 63-1908 selectively blocked recombinant receptors expressed in Xenopus oocytes containing NR1C + NR2B subunits with an IC(50) of 0.003 microM and those containing NR1C + NR2A subunits with an IC(50) of >100 microM, thus demonstrating greater than 20,000-fold selectivity for the recombinant receptors expressing NR1C + NR2B. Ro 63-1908 blocked these NMDA NR2B-subtype receptors in an activity-dependent manner. Ro 63-1908 was neuroprotective against glutamate-induced toxicity and against oxygen/glucose deprivation-induced toxicity in vitro with IC(50) values of 0.68 and 0.06 microM, respectively. Thus, the in vitro pharmacological characterization demonstrated that Ro 63-1908 was a potent and highly selective antagonist of the NR2B subtype of NMDA receptors. Ro 63-1908 was active against sound-induced seizures (ED(50) = 4.5 mg/kg i.p. when administered 30 min beforehand) in DBA/2 mice. The dose required to give a full anticonvulsant effect did not produce a deficit in the Rotarod test. NMDA-induced seizures were also inhibited by Ro 63-1908 with an ED(50) of 2.31 mg/kg i.v. when administered 15 min before testing. Ro 63-1908 gave a dose-related neuroprotective effect against cortical damage in a model of permanent focal ischemia. Maximum protection of 39% was seen at a plasma concentration of 450 ng/ml. There were, however, no adverse cardiovascular or CNS side-effects seen at this dosing level.

Acoustic Stimulation↗

PubMed2002

[Tumor biology of primary breast cancer and minimal residual disease].

The immunocytochemical detection of isolated disseminated tumor cells (ITC) in the bone marrow of breast cancer patients, what is called minimal residual disease (MRD), has been demonstrated to be of prognostic value in all stages of the disease. In order to definitely prove the origin of these cells from the primary tumor it is necessary to identify common factors on both tumor tissue and ITC, furthermore a more detailed characterization could help to improve their prognostic impact by defining certain subgroups and possibly establish new therapeutic strategies. We examined the expression/amplification of HER2neu, CD 44 adhesion molecule and CD 31 angiogenetic factor on more than 200 primary tumor tissues by immunohistochemistry or fluorescence in situ hybridisation, resp., and found no sign. correlation with the detection of ITC. After a median follow-up of 32 months only ITC in the bone marrow were of prognostic significance. In a small number of patients we examined the expression of topoisomerase II alpha, a key enzyme of DNA replication, and its predictive value of eliminating ITC by anthracyclin based chemotherapy. No correlation with the presence of ITC before or after chemotherapy could be found, yet pat. with topoisomerase II alpha neg. tumors showed a trend to reduced disease free survival. Because of the very low number of ITC per bone marrow sample, the direct characterization of these factors on ITC stays difficult without the possibility of tumor cell enrichment or cell culture. Preliminary results on multi colour stained samples indicate that a selection of certain biological factors takes place during tumor cell dissemination.

Bone Marrow↗

PubMed2001

Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements.

Intact actin microfilaments are required for insulin-regulated glucose transporter isoform 4 (GLUT4) translocation to the plasma membrane. Lipoxygenase (LO) metabolites have recently been shown to contribute to the regulation of actin cytoskeleton rearrangement. In the present investigation, ventricular cardiomyocytes were used to study the effects of two structurally different LO inhibitors (esculetin and nordihydroguaiaretic acid) on insulin signalling events, glucose uptake, GLUT4 translocation and the actin network organization. Insulin stimulation increased glucose uptake 3-fold in control cells, whereas LO inhibition completely blocked this effect. This was paralleled by a slight reduction in the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2. However, inhibition of 12-LO did not affect the association of phosphatidylinositol 3-kinase with IRS-1 and the phosphorylation of Akt/protein kinase B in response to insulin. Addition of 12(S)-hydroxyeicosatetraenoic acid almost completely restored the insulin action in cells exposed to nordihydroguaiaretic acid. Insulin stimulation increased cell surface GLUT4 2-fold in control cells, whereas LO inhibition abrogated the insulin-stimulated GLUT4 translocation. LO inhibition induced a prominent disassembly of actin fibres compared with control cells. In conclusion, we show here that 12(S)-hydroxyeicosatetraenoic acid plays a role in the organization of the actin network in cardiomyocytes. LO inhibition blocks GLUT4 translocation without affecting downstream insulin signalling. These data suggest that LO metabolites participate in the regulation of glucose transport by contributing to a rearrangement of actin cytoskeletal elements.

Actins↗

PubMed2001

Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1.

BACKGROUND: Most patients with lymph node-negative breast cancer are cured by locoregional treatment; however, about 30% relapse. Because traditional histomorphologic and clinical factors fail to identify the high-risk patients who may benefit from adjuvant chemotherapy, other prognostic factors are needed. In a unicenter study, we have found that levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in the primary tumor are predictive of disease recurrence. Thus, we designed the Chemo N(0) prospective randomized multicenter therapy trial to investigate further whether uPA and PAI-1 are such prognostic factors and whether high-risk patients identified by these factors benefit from adjuvant chemotherapy. After 4.5 years, we present results of the first interim analysis. METHODS: We studied 556 patients with lymph node-negative breast cancer. The median follow-up was 32 months. All patients with low tumor levels of uPA (< or = 3 ng/mg of protein) and of PAI-1 (< or = 14 ng/mg of protein) were observed. Patients with high tumor levels of uPA (> 3 ng/mg of protein) and/or of PAI-1 (> 14 ng/mg of protein) were randomly assigned to combination chemotherapy or subjected to observation only. All statistical tests were two-sided. RESULTS: A total of 241 patients had low levels of uPA and PAI-1, and 315 had elevated levels of uPA and/or PAI-1. The estimated 3-year recurrence rate for patients with low tumor levels of uPA and PAI-1 (low-risk group) was 6.7% (95% confidence interval [CI] = 2.5% to 10.8%). This rate for patients with high tumor levels of uPA and/or PAI-1 (high-risk group) was 14.7% (95% CI = 8.5% to 20.9%) (P = 0.006). First interim analysis suggests that high-risk patients in the chemotherapy group benefit, with a 43.8% lower estimated probability of disease recurrence at 3 years than high-risk patients in the observation group (intention-to-treat analysis: relative risk = 0.56; 95% CI = 0.25 to 1.28), but further follow-up is needed for confirmation. CONCLUSIONS: Using uPA and PAI-1, we have been able to classify about half of the patients with lymph node-negative breast cancer as low risk, for whom adjuvant chemotherapy may be avoided, and half as high risk, who appear to benefit from adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Integrin alpha(v)beta(3)/vitronectin interaction affects expression of the urokinase system in human ovarian cancer cells.

The urokinase type plasminogen activator (uPA), together with its receptor uPAR and the plasminogen activator inhibitor type-1 (PAI-1) plays a pivotal role during tumor invasion and metastasis. Integrins, via interaction with the extracellular matrix (ECM), control cell adhesion and motility. The two systems are functionally linked because uPAR and PAI-1 bind to the ECM component vitronectin (VN). Because integrin signaling alters gene expression patterns, we investigated whether the expression levels of uPA, uPAR, and PAI-1 are affected by ECM/integrin interactions. Expression of uPA, uPAR, and PAI-1 was significantly enhanced when human ovarian cancer cells (OV-MZ-6) were cultivated on fibronectin or collagen type IV. In contrast, VN induced down-regulation of uPA and uPAR while increasing PAI-1 by up to 4-fold. VN-dependent decrease of uPA protein was paralleled by a significant reduction of uPA promoter activity that was even more pronounced upon alpha(v)beta(3) overexpression and depended on the presence of intact Rel protein-binding sites. The activity of Rel transcription factors was also significantly reduced upon alpha(v)beta(3)-mediated cell adhesion to VN. The activity of the Rel-unresponsive PAI-1 promoter was up to 5-fold induced as a function of alpha(v)beta(3)/VN interaction. Thus, the balance between available concentrations of uPA, uPAR, PAI-1, and integrins in human ovarian cancer cells might provide a switch within the regulation of their invasive phenotype.

Female↗

PubMed2001

Preservation of venous endothelial function in the forearm venous capacitance bed of patients with chronic heart failure despite arterial endothelial dysfunction.

OBJECTIVES: The goal of this study was to assess whether endothelial dysfunction occurs in the forearm venous capacitance bed of patients with chronic heart failure (CHF) and to determine the role of nitric oxide (NO) in modulating venous tone. BACKGROUND: Control of venous tone is crucially important in CHF. More than 70% of blood volume lies in the venous capacitance beds. Therefore, small changes in venous tone may markedly affect cardiac filling pressures and cardiac output. METHODS: Venous tone was measured using radionuclide forearm venous plethysmography in 24 patients with CHF and 16 age-matched controls. The effect of basal NO activity on venous tone was assessed by infusing N-monomethyl-L-arginine 12 mg/min and stimulated NO using carbachol 15 microg/min. Brachial artery flow-mediated dilation was assessed by ultrasonic wall-tracking. RESULTS: Blockade of basal NO release caused a significant and similar venoconstriction in patients (9.6 +/- 1.8%, p < 0.01) and controls (6.6 +/- 1.7%, p < 0.01). Carbachol-induced venodilation was significant and similar in patients (36.8 +/- 3.9%, p < 0.001) and controls (40.7 +/- 3.9%, p < 0.001). Brachial artery flow-mediated dilation was impaired in patients compared with controls (2.0 +/- 0.6% vs. 7.5 +/- 2.5%, p < 0.01). CONCLUSIONS: Our data indicate that, despite marked impairment of the function of the arterial endothelium, there is preservation of both basal and stimulated NO release in the forearm venous capacitance bed. This may provide important insights into mechanisms of endothelial dysfunction in CHF and the potential for novel therapy.

Aged↗