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ABSTRACT: Herz-Kreislauf-Erkrankungen, wie z.B. die koronare
Herzkrankheit, gehören zu den führenden Ursachen
der Morbidität und Mortalität in den westlichen Industrienationen.
Dabei steht die kardiovaskuläre
Mortalität in enger Beziehung zu strukturellen und
funktionellen Veränderungen der arteriellen Gefäßwand.
Die wichtigste funktionelle Veränderung des
Gefäßbaums ist die Zunahme der arteriellen Gefäßsteifigkeit
oder auch reziprok die Abnahme der Gefäßelastizität.
Die Zunahme der arteriellen Gefäßsteifigkeit
ist aber nicht nur „Spiegel“ des „overall
atherosclerotic load“, sondern beeinflusst ihrerseits
die Herz-Kreislauf-Funktion negativ.
In dieser Übersicht werden die pathophysiologische
Grundlage der arteriellen Gefäßfunktion und
ihre Bedeutung für die kardiovaskuläre Mortalität
dargestellt. Nichtinvasive Verfahren zur Untersuchung
der arteriellen Gefäßfunktion werden erläutert
und der prädiktive Wert dieser Parameter für das
kardiovaskuläre Risiko diskutiert.
Cardiovascular diseases such as coronary heart disease
are the leading cause for morbidity and mortality in
industrial countries. Current evidence shows that stiffening
of the arterial wall is one major mechanism responsible
for this morbidity and mortality in cardiovascular
disease.
Various physiological and pathophysiological parameters
influence arterial stiffening including age,
gender, blood pressure, smoking, and diseases such as
hypertension, diabetes, renal failure, and hypercholesterolemia.
Thus, the assessment of arterial stiffness
has become a widely used tool to investigate the
function of the arteries in epidemiologic and clinical
studies. Traditionally, arterial stiffness has been assessed
by pulse wave velocity, a noninvasive parameter
which has been shown to predict cardiovascular
mortality. In addition, pulse wave analysis has been
increasingly used to determine the augmentation index,
a parameter that describes the effect of pulse
wave reflection on the central aortic pressure configuration.
In the present review, the pathophysiological
contribution of arterial stiffening for cardiovascular
morbidity and mortality is described. Details of models,
indices, and techniques used to evaluate stiffness
will be presented. Clinical studies investigating
the predictive value of stiffness markers in defining
future cardiovascular risk and survival are summarized.
Herz 04/2012; 32(5):379-386. · 0.92 Impact Factor
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ABSTRACT: Despite the introduction of arterial stiffness measurements in the European recommendation, pulse wave velocity (PWV) and augmentation index (AI) are still not used routinely in clinical practice. It would be of advantage if such measurements were done in the sitting position as is done for blood pressure. The aim of this study was to evaluate whether there is a difference in stiffness parameters in sitting vs. supine position. Arterial stiffness was measured in 24 healthy volunteers and 20 patients with cardiovascular disease using three different devices: SphygmoCor (Atcor Medical, Sydney, Australia), Arteriograph (TensioMed, Budapest, Hungary) and Vascular Explorer (Enverdis, Jena, Germany). Three measurements were performed in supine position followed by three measurements in sitting position. Methods were compared using correlation and Bland-Altman analysis. There was a significant correlation between PWV in supine and sitting position (Arteriograph: P<0.0001, r=0.93; Vascular Explorer; P<0.0001, r=0.87). There were significant correlations between AI sitting and AI supine using Arteriograph (P<0.0001, r=0.97), Vascular Explorer (P<0.0001, r=0.98) and SphygmoCor (P<0.0001, r=0.96). When analyzed by Bland-Altman, PWV and AI measurements in supine vs. sitting showed good agreement. There was no significant difference in PWV obtained with the three different devices (Arteriograph 7.5±1.6 m s(-1), Vascular Explorer 7.3±0.9 m s(-1), SphygmoCor 7.0±1.8 m s(-1)). AI was significantly higher using the Arteriograph (17.6±15.0%) than Vascular Explorer and SphygmoCor (10.2±15.1% and 10.3±18.1%, respectively). The close agreement between sitting and supine measurements suggests that both PWV and AI can be reliably measured in the sitting position.
Hypertension Research 10/2010; 34(2):202-8. · 2.58 Impact Factor
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ABSTRACT: measuring arterial stiffness using pulse wave velocity (PWV) has become an important tool to assess vascular function and cardiovascular mortality. For subject with hypertension, end-stage renal disease and diabetes, PWV has been shown to predict cardiovascular and all-cause mortality. We hypothesize that PWV would also predict mortality in subjects who have undergone kidney transplantation.
a cohort of 330 patients with renal transplantation was studied with a mean age at entry 51.4 ± 0.75 years. Mean follow-up was 3.8 years (± 0.7 years); 16 deaths occurred during follow-up. At entry, together with standard clinical and biochemical parameters, PWV was determined from pressure tracing over carotid and femoral arteries.
with increasing PWV, there was a significant increase in age, systolic blood pressure and pulse pressure. In addition, subjects with higher PWV also exhibited more frequently the presence of coronary heart disease. On the basis of Cox analyses, PWV and systolic blood pressure emerged as predictors of all-cause mortality.
these results provide evidence that PWV is a strong predictor of all-cause mortality in the population of renal transplant recipients.
European journal of medical research 10/2010; 15(10):452-5. · 1.13 Impact Factor
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ABSTRACT: Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and renal impairment. Often HUS is triggered by Shiga-like toxin- producing ESCHERICHIA COLI. Less common is atypical HUS (aHUS), which is caused by defective complement control. aHUS is associated with mutations in genes encoding complement regulatory proteins in ~50% of patients with this syndrome. Furthermore, autoantibodies that inactivate to factor H have also been linked to the disease. Initial triggers include infections, use of endothelial-affecting drugs, malignancies, transplantation, and pregnancy. Advances in our understanding of the pathogenesis of atypical HUS suggest that complement inhibition may be used as treatment for the disease. We discuss the potential benefit of the complement inhibitor eculizumab for the treatment of aHUS.
Seminars in Thrombosis and Hemostasis 09/2010; 36(6):669-72. · 4.52 Impact Factor
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Gerd Walz,
Klemens Budde,
Marwan Mannaa, Jens Nürnberger,
Christoph Wanner,
Claudia Sommerer,
Ulrich Kunzendorf,
Bernhard Banas,
Walter H Hörl,
Nicholas Obermüller,
Wolfgang Arns,
Hermann Pavenstädt,
Jens Gaedeke,
Martin Büchert,
Christoph May,
Harald Gschaidmeier,
Stefan Kramer,
Kai-Uwe Eckardt
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ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a slowly progressive hereditary disorder that usually leads to end-stage renal disease. Although the underlying gene mutations were identified several years ago, efficacious therapy to curtail cyst growth and prevent renal failure is not available. Experimental and observational studies suggest that the mammalian target of rapamycin (mTOR) pathway plays a critical role in cyst growth.
In this 2-year, double-blind trial, we randomly assigned 433 patients with ADPKD to receive either placebo or the mTOR inhibitor everolimus. The primary outcome was the change in total kidney volume, as measured on magnetic resonance imaging, at 12 and 24 months.
Total kidney volume increased between baseline and 1 year by 102 ml in the everolimus group, versus 157 ml in the placebo group (P=0.02) and between baseline and 2 years by 230 ml and 301 ml, respectively (P=0.06). Cyst volume increased by 76 ml in the everolimus group and 98 ml in the placebo group after 1 year (P=0.27) and by 181 ml and 215 ml, respectively, after 2 years (P=0.28). Parenchymal volume increased by 26 ml in the everolimus group and 62 ml in the placebo group after 1 year (P=0.003) and by 56 ml and 93 ml, respectively, after 2 years (P=0.11). The mean decrement in the estimated glomerular filtration rate after 24 months was 8.9 ml per minute per 1.73 m2 of body-surface area in the everolimus group versus 7.7 ml per minute in the placebo group (P=0.15). Drug-specific adverse events were more common in the everolimus group; the rate of infection was similar in the two groups.
Within the 2-year study period,as compared with placebo, everolimus slowed the increase in total kidney volume of patients with ADPKD but did not slow the progression of renal impairment [corrected]. (Funded by Novartis; EudraCT number, 2006-001485-16; ClinicalTrials.gov number, NCT00414440.)
New England Journal of Medicine 08/2010; 363(9):830-40. · 53.30 Impact Factor
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ABSTRACT: Ischemia remains the most common cause of acute kidney injury (AKI). Decreased intercellular adhesion and alterations in adhesion molecules may contribute to the loss of renal function observed in AKI. In the present study, we evaluated the distribution of adhesion molecules in the human kidney and analyzed their expression in human and experimental AKI. Specimens of human kidneys obtained from patients with and without AKI were stained for the cell adhesion molecules E-cadherin, N-cadherin and beta-catenin. Experimental AKI in rats was induced by renal artery clamping. Immunostaining and immunoblotting were carried out for E-cadherin, N-cadherin and beta-catenin. Proximal tubule cells from opossum kidneys (OKs) were used to analyze the effect of chemical hypoxia (ATP depletion) in vitro. In the adult human kidney, N-cadherin was expressed in proximal tubules, while E-cadherin was expressed in other nephron segments. beta-Catenin was expressed in both proximal and distal tubules. In human AKI and in ischemic rat kidneys, N-cadherin immunostaining was depleted from proximal tubules. There was no change in E-cadherin or beta-catenin. In vitro, OK cells expressed N-cadherin only in the presence of collagen, and ATP depletion led to a depletion of N-cadherin. Collagen IV staining was reduced in ischemic rat kidneys compared to controls. The results of the study suggest that N-cadherin may play a significant role in human and experimental AKI.
Histochemie 06/2010; 133(6):641-9. · 2.59 Impact Factor
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ABSTRACT: An inappropriate activation of the mTOR pathway was demonstrated in the autosomal dominant (AD) form of polycystic kidney disease (PKD). To date it is unclear whether the mTOR pathway is activated in autosomal-recessive (AR) PKD, a cystic disease which occurs in childhood. The purpose of the present study was to evaluate the mTOR pathway in AR PKD.
We evaluated the expression of mTOR pathway molecules in paraffin-embedded liver and kidney samples from patients with AR PKD and control specimens from animals as well as humans. Monoclonal antibodies, the phosphorylated proteins pmTOR, pS6-ribosomal-protein (pS6K), p4E-BP1, peIF4G, and phospho-tuberin/TSC2 were used.
mTOR was strongly expressed in renal cyst-lining cells and bile ducts from AR PKD specimen. S6K immunostaining was strong in smaller tubules and weak both in larger renal cysts and in the bile duct epithelium. In controls, mTOR and S6K were expressed in distal tubule segments. 4E-BP1-immunostaining was restricted to noncystic tubules in AR PKD. eIFG4-immunostaining was observed in bile duct epithelium in AR PKD, but not in control tissue. Tuberin/TSC2 immunostaining was negative in all specimens.
Our data suggest that the mTOR pathway may be activated in AR PKD, and mTOR molecules may represent a potential target to slow down cyst development in this disease.
Kidney and Blood Pressure Research 01/2010; 33(2):129-38. · 1.46 Impact Factor
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Jens Nürnberger,
Thomas Philipp,
Oliver Witzke,
Anabelle Opazo Saez,
Udo Vester,
Hideo Andreas Baba,
Andreas Kribben,
Lothar Bernd Zimmerhackl,
Andreas R Janecke,
Mato Nagel,
Michael Kirschfink
New England Journal of Medicine 02/2009; 360(5):542-4. · 53.30 Impact Factor
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ABSTRACT: Proximal tubules subjected to hypoxia in vitro under conditions relevant to ischaemia in vivo develop an energetic deficit that is not corrected even after full reoxygenation. We have provided evidence that accumulation of nonesterified fatty acids (NEFA) is the primary reason for this energetic deficit. In this study, we have further investigated the mechanism for the NEFA-induced energetic deficit.
Mitochondrial membrane potential (Deltapsi) was measured in digitonin-permeabilized, freshly isolated proximal tubules by safranin O uptake. Addition of the potassium/proton exchanger nigericin enables the determination of the mitochondrial proton motive force (Deltap) and the proton gradient (DeltapH). ATP was measured luminometrically and NEFA colorimetrically.
Tubule ATP content was depleted after hypoxia and recovered incompletely, even after full reoxygenation. Mitochondrial safranin O uptake was decreased in proximal tubules after hypoxia and reoxygenation (H/R). This decrease was attenuated by delipidated bovine serum albumin (dBSA) or citrate. Addition of nigericin increased safranin O uptake of mitochondria in normoxic proximal tubules, but not in proximal tubules after H/R. Addition of dBSA restored the effect of nigericin to increase mitochondrial safranin O uptake. Addition of the NEFA oleate had the same impact on mitochondrial safranin O uptake as subjecting proximal tubules to H/R.
The mechanism of the NEFA-induced energetic deficit in freshly isolated rat proximal tubules induced by H/R is characterized by impaired ATP production after full reoxygenation, impaired recovery of Deltapsi and Deltap, abrogation of DeltapH and sensitivity to citrate, consistent with involvement of the tricarboxylate carrier. The data support the concept that protonophoric uncoupling by NEFA movement on anion carriers plays a critical role in proximal tubule mitochochondrial dysfunction after H/R.
Nephrology Dialysis Transplantation 09/2008; 24(1):43-51. · 3.40 Impact Factor
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ABSTRACT: New onset diabetes (NODM) is a common and serious complication of kidney transplantation, and is associated with increased cardiovascular morbidity and mortality. Cardiovascular morbidity and mortality, in turn, are closely associated with arterial stiffening. We hypothesize that NODM may be associated with an increase in arterial stiffness in renal transplantation. We compared pulse wave velocity (PWV) and augmentation index in 318 renal transplant patients with (n = 57) and without NODM (n = 261). PWV was determined from pressure tracing over carotid and femoral arteries. Augmentation-index was derived by pulse-wave-analysis using radial applanation tonometry. PWV was significantly higher in transplant recipients with NODM (10.5 m/s) compared with transplant patients without NODM (8.7 m/s, P = 0.0002). There was no difference in augmentation index between patients with (27.7%) and without NODM (28.1%, P = 0.87). When analyzed by multiple regression analysis, PWV was only significantly correlated to age (P < 0.0001), NODM (P = 0.0325), and systolic blood pressure (P = 0.0081). NODM in renal transplant patients may accelerate arterial stiffening, thereby contributing to cardiovascular morbidity and mortality.
Transplant International 07/2008; 21(10):930-5. · 2.92 Impact Factor
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Journal of Hypertension 07/2008; 26(6):1267. · 4.02 Impact Factor
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Nephrology Dialysis Transplantation 06/2008; 23(9):3026-9. · 3.40 Impact Factor
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ABSTRACT: The ambulatory arterial stiffness index (AASI) is a new index that reflects the dynamic relation between diastolic and systolic blood pressure through the circadian blood pressure rhythm. It was the aim of this study to investigate the association between AASI, dipping status and pulse pressure as a classical indicator of arterial stiffness in normotensive and hypertensive subjects.
One hundred and twelve individuals were evaluated for a kidney donation to a relative at the University Hospital Essen, Germany. In this context routine 24-h ambulatory blood pressure measurements were performed. A nocturnal reduction in diastolic blood pressure of >10% was defined as 'dipping'. We determined the diurnal and nocturnal blood pressure and brachial pulse pressure values and computed AASI for each participant.
AASI was a strong predictor for diastolic and systolic nocturnal blood pressure fall (r = -0.55 and -0.48, respectively; P < 0.001). Additionally, AASI predicted the status of 'dipping/nondipping'. 'Dippers' showed significantly lower AASI than 'nondippers' in both normotensive and hypertensive subjects. Dippers, but not nondippers, demonstrated an association between AASI and brachial pulse pressure.
AASI is strongly correlated with nocturnal blood pressure fall and is increased in nondipping independent of blood pressure. The role of AASI as a potential marker for arterial stiffness depends, in this study, on the characterization of the dipping status.
Journal of Hypertension 02/2008; 26(2):210-4. · 4.02 Impact Factor
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ABSTRACT: Ezetimibe has shown efficacy in the therapy of hypercholesterolemia in renal transplant patients. This is the first study investigating the effect of ezetimibe on renal function in kidney transplant recipients.
Fifty-six patients with statin-resistant hypercholesterolemia (total cholesterol >200 mg/dl) after renal transplantation received additional ezetimibe therapy (10 mg/day) for 12 months. A group receiving statin therapy (n=28) served as controls in this prospective study.
Total cholesterol and LDL cholesterol concentrations decreased significantly in the ezetimibe-treated patients but remained stable in the control group (delta total cholesterol: -24+/-49 mg/dl vs 19+/-49 mg/dl, P<0.01; delta LDL: -30+/-39 mg/dl vs -3+/-31 mg/dl, P<0.01). Mean creatinine clearance remained stable in ezetimibe-treated patients but decreased significantly in control group (delta Cockcroft-Gault: 0.9+/-7.3 ml/min vs - 4.8+/-12.8 ml/min, P=0.025; delta Modification of Diet in Renal Disease: -0.4+/-6.2 ml/min/1.73 m(2) vs 4.7+/-8.8 ml/min/1.73 m(2), P=0.033).
The data of our prospective case-control study suggest that ezetimibe appears to ameliorate the decline of renal function after renal transplantation.
Nephrology Dialysis Transplantation 01/2008; 23(1):369-73. · 3.40 Impact Factor
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ABSTRACT: Cardiovascular diseases such as coronary heart disease are the leading cause for morbidity and mortality in industrial countries. Current evidence shows that stiffening of the arterial wall is one major mechanism responsible for this morbidity and mortality in cardiovascular disease. Various physiological and pathophysiological parameters influence arterial stiffening including age, gender, blood pressure, smoking, and diseases such as hypertension, diabetes, renal failure, and hypercholesterolemia. Thus, the assessment of arterial stiffness has become a widely used tool to investigate the function of the arteries in epidemiologic and clinical studies. Traditionally, arterial stiffness has been assessed by pulse wave velocity, a noninvasive parameter which has been shown to predict cardiovascular mortality. In addition, pulse wave analysis has been increasingly used to determine the augmentation index, a parameter that describes the effect of pulse wave reflection on the central aortic pressure configuration. In the present review, the pathophysiological contribution of arterial stiffening for cardiovascular morbidity and mortality is described. Details of models, indices, and techniques used to evaluate stiffness will be presented. Clinical studies investigating the predictive value of stiffness markers in defining future cardiovascular risk and survival are summarized.
Herz 09/2007; 32(5):379-86. · 0.92 Impact Factor
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ABSTRACT: The renin-angiotensin aldosterone system (RAAS) plays a key role in the regulation of blood pressure, acting via the effects of the hormone angiotensin (Ang) II. Ang II increases blood pressure and can exert growth-promoting effects leading to end-organ damage. Excess RAAS activity has been shown to be a major underlying cause of hypertension, heart failure, and related cardiovascular disorders. Inhibitors of renin block the RAAS at its first and rate-limiting step and thus appear to offer an excellent opportunity for blood pressure control. In the past two decades various potential renin inhibitors have been developed but have not been clinically useful. This review discusses a recent patent in the development of a novel class of non-peptide renin inhibitors: an alkanecarboxamide, aliskiren (SPP-100; Novartis). Aliskiren is effective in animal models, while recent results from studies in humans indicate that aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension.
Recent Patents on Cardiovascular Drug Discovery 12/2006; 1(3):233-40.
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ABSTRACT: Nephronophthisis is a common genetic cause of end-stage renal disease in childhood. Recently, Invs was identified as the gene mutated in the infantile form of nephronophthisis. Humans with nephronophthisis develop a large number of extrarenal manifestations, including situs variations, anomalies of the hepatobiliary system, retinal degeneration and cerebellar ataxia. Mice homozygous for a mutation in the Invs gene (inv mouse) die during the first week after birth as a result of renal and liver failure. Although organ anomalies have been characterized in human nephronophthisis and the inv mouse, little is known about the tissue expression of the Invs gene product, inversin. We have used laser confocal microscopy of paraffin-embedded murine tissue sections to provide the first detailed characterization of the distribution of inversin in various organs. Our results show that inversin is localized to distal tubules in the kidney, hepatic bile ducts, acinar and ductal pancreatic cells, epithelial intestinal cells, splenic germinal centres, bronchiolar epithelial cells, dendrites of cerebellar Purkinje cells, retinal neural cells and spermatocytes and spermatids in the testis. The localization of inversin in distal tubules in the kidney and in extrarenal tissues suggests that the expression of this protein has an important function in a variety of organs. Further studies are required to understand the way in which mutations in the Invs gene lead to the multi-organ pathology of inv mouse and human nephronophthisis.
Cell and Tissue Research 02/2006; 323(1):147-55. · 3.11 Impact Factor
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ABSTRACT: A C825T polymorphism has been identified for the gene encoding the G-protein beta 3 subunit ( GNB3 ). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T-786C polymorphism of the gene for endothelial nitric oxide synthase ( NOS3 ) on insulin-mediated venous responses.
We used the linear variable transducer technique to compare dorsal hand vein compliance in 31 young, healthy men ( GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T-786C: 14 TT, 13 TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2-10,000 ng/min) were established, and veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50-250,000 microU/min), and the changes in venous diameter were recorded.
Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T-786C-allele carrier status had no influence on insulin-induced vascular responses ( P = .60 for TC/CC versus TT).
This study is the first to show the influence of a genetic polymorphism on insulin-mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender-specific differences remain to be investigated.
Clinical Pharmacology & Therapeutics 07/2005; 77(6):495-502. · 6.04 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the repeatability of forearm skin blood flow responses to intradermal injections of acetylcholine (ACh) and endothelin-1 (ET-1) using a double injection technique (DIT) and a laser Doppler imager (LDI) scanner in the human skin microcirculation.
We used a laser Doppler imager (Moor LDI V3.01) to continuously monitor the change in skin blood flow during intradermal administration of physiological saline (0.9% NaCl), acetylcholine (ACh 10(-7), 10(-8), 10(-9) M) and endothelin-1 (ET-1 10(-14), 10(-16), 10(-18) M) in 10 healthy male subjects. Subjects were examined on 3 different days for assessment of interday and interobserver repeatability. Injections of either drug were randomly placed on different sites of the forearm. Laser Doppler images were collected before and after injection at 2.5 min intervals for 30 min. Data were analysed after the completion of each experiment using Moor Software V.3.01. Results are expressed as changes from baseline in arbitrary perfusion units (PU).
ACh caused a significant vasodilation (P < 0.0001 anova, mean +/- SE: 766 +/- 152 PU, ACh 10(-9) M; 1868 +/- 360 PU, ACh 10(-8) M; 4188 +/- 848 PU, ACh 10(-7) M; mean of days 1 and 2, n = 10), and ET-1 induced a significant vasoconstrictive response (P < 0.0001 anova, -421 +/- 83 PU, ET-1 10(-18) M; -553 +/- 66 PU, ET-1 10(-16) M; -936 +/- 90 PU, ET-1 10(-14) M; mean of days 1 and 2, n = 10). There was no difference on the response to either drug on repeated days. Bland-Altman analyses showed a close agreement of responses between days with repeatability coefficients of 1625.4 PU for ACh, and 386.0 PU for ET-1 (95% CI: ACh, -1438 to 1747 PU, ET-1, -399 to 358 PU) and between observers with repeatability coefficients of 1057.2 PU for ACh and 255.8 PU for ET-1 (95% CI: ACh, -1024 to 1048 PU, ET-1, -252 to 249 PU). The variability between these responses was independent of average flux values for both ACh and ET-1. There was a significant correlation between responses measured in the same site, in the same individual on two different days by the same observer (ACh, r = 0.94, P < 0.0001; ET-1, r = 0.90, P < 0.0006), and between responses measured by two different observers (ACh, r = 0.94, P < 0.0001; ET-1, r = 0.91, P < 0.0003).
We have shown that interday and intraobserver responses to intradermal injections of ET-1 and ACh, assessed using the DIT in combination with an LDI scanner, exhibited good reproducibility and may be a useful tool for studying the skin microcirculation in vivo.
British Journal of Clinical Pharmacology 05/2005; 59(5):511-9. · 2.96 Impact Factor
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ABSTRACT: Clonidine is a classical sympatholytic drug that is widely used for the treatment of hypertension. Experimental and clinical studies suggest that Clonidine may activate baroreflex. The aim of this study was to determine the hemodynamic response to Clonidine under physiological conditions and to test the hypothesis that Clonidine would reduce cardiac output and blood pressure resulting in an increase in total peripheral resistance.
Clonidine's hemodynamic effect was evaluated in 28 young, healthy subjects after a single i.v. dose of 1 microg x kg(- 1). Impedance cardiography, systolic time intervals and pulse wave analysis were used to characterize myocardial and vascular function.
Clonidine lowered blood pressure, heart rate, left ventricular ejection time, and pulse wave velocity and increased pre-ejection period. Stroke volume and cardiac output decreased gradually over the investigation time of 240 min. Central systolic blood pressure (SBP) was lowered to a larger extent than peripheral SBP. Total peripheral resistance was characterized by an immediate fall of short duration followed by a continuous rise above baseline after 120 min. Placebo did not have any significant effect on hemodynamic parameters.
Clonidine's blood pressure lowering effect is mediated by both an immediate decrease in vascular resistance and a prolonged decrease in cardiac output, and Clonidine lowers central SBP more than peripheral SBP.
Cardiovascular Drugs and Therapy 02/2005; 19(1):49-55. · 3.13 Impact Factor
