MRSA endocarditis--postcardiac surgery.
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Aged, 80 and over↗
Biomedical subjects
Matthias Schmitt
Publications and source records attributed to Matthias Schmitt.
Basal NO locally modulates human iliac artery function in vivo.
We demonstrated previously that endogenous NO influences large-artery distensibility in the ovine hindlimb. However, the role of basal NO in larger human conduit arteries is controversial. The aim of this study was to investigate whether basal production of NO, acting locally, influences iliac artery distensibility in humans. Distensibility was assessed by intra-arterial measurement of the pulse wave velocity. Eighteen subjects, free of significant coronary or iliac artery disease, were studied after diagnostic cardiac catheterization. Simultaneous pressure waveforms were recorded with a high-fidelity dual-pressure sensing catheter, placed in the common iliac artery during intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min), or NG-monomethyl-L-arginine (8 and 16 micromol/min). Drugs were infused proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath, to control for any reflex changes in flow or sympathetic activation. Velocity was calculated using the foot-to-foot methodology. Six subjects received glyceryl trinitrate and 12 NG-monomethyl-L-arginine. There was no change in velocity after infusion of glyceryl trinitrate or NG-monomethyl-L-arginine via the sheath. However, infusion of glyceryl trinitrate via the catheter significantly reduced velocity by 31.43+/-5.80% (mean+/-SEM; P<0.01; P=0.02 for comparison). Likewise, infusion of the highest dose of NG-monomethyl-L-arginine via the catheter significantly increased velocity by 27.25+/-8.20% (P=0.001; P=0.02 for comparison). Importantly, there was no change in mean arterial blood pressure throughout the studies. These data indicate that under resting conditions, local NO production modulates human iliac artery distensibility and that exogenous NO increases arterial distensibility.
Blood Flow Velocity↗
Effects of aldosterone on forearm vasculature in treated chronic heart failure.
The nongenomic effects of aldosterone in disease states associated with endothelial dysfunction may differ from those in healthy subjects. The effects of locally infused aldosterone on the forearm blood flow and volume were studied in optimally treated patients with chronic heart failure (CHF). At baseline and after incremental intrabrachial aldosterone, forearm blood flow was assessed using conventional strain gauge plethysmography, and forearm venous volume was assessed by radionuclide plethysmography. Constriction of the resistance vasculature of the forearm without significant effect on forearm venous capacitance was demonstrated in response to aldosterone in patients treated for CHF.
Aged↗
Nebivolol increases arterial distensibility in vivo.
Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. beta-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that beta-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of beta-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating beta-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6+/-3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of -1+/-3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of -5+/-3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of N(G)-monomethyl-L-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a beta2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.
Adrenergic beta-Antagonists↗
Effects of exogenous and endogenous natriuretic peptides on forearm vascular function in chronic heart failure.
OBJECTIVE: Natriuretic peptides (NPs) reduce central venous pressure in patients with chronic heart failure (cHF) despite attenuation of arterial, renal, and humoral effects. This suggests a preserved venodilator response. This study had 4 aims: to compare the venodilator effects of human NPs in patients with cHF; to assess the contribution of basal ANP and BNP levels to regulation of forearm vascular volume (FVV); to test the hypothesis that venous ANP responsiveness is preserved in cHF; and to assess the involvement of endothelial nitric oxide-synthase (eNOS) in NP-induced vascular effects. METHODS AND RESULTS: Venous and arterial forearm vascular responses to incremental intra-arterial doses of ANP, Urodilatin, BNP, CNP, or the ANP receptor antagonist A71915 were studied in 53 patients and 11 controls. ANP receptor antagonism reduced FVV by 4.4%+/-1.2% (P<0.05). The forearm blood flow (FBF) response to ANP was significantly blunted in patients versus controls (P<0.01), whereas FVV increased similarly in both groups (maximum 14.7% and 13.4%, both P<0.001). The eNOS blockade reduced ANP-induced FBF changes in controls but not in patients (P<0.05), whereas similar reductions in FVV changes were seen in groups (both P<0.001). CONCLUSIONS: In cHF venous, but not arterial, ANP responsiveness is preserved. Arterial endothelial dysfunction may contribute to NP resistance.
Adult↗
Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy men.
AIMS: Alpha-lipoic acid (ALA) is a thiol compound with antioxidant properties used in the treatment of diabetic polyneuropathy. ALA may also improve arterial function, but there have been scant human trials examining this notion. This project aimed to investigate the effects of oral and intra-arterial ALA on changes in systemic and regional haemodynamics, respectively. METHODS: In study 1, 16 healthy older men aged 58 +/- 7 years (mean +/- SD) received 600 mg of ALA or placebo, on two occasions 1 week apart, in a randomized cross-over design. Repeated measures of peripheral and central haemodynamics were then obtained for 90 min. Central blood pressure and indices of arterial stiffness [augmentation index (AIx) and estimated aortic pulse wave velocity] were recorded non-invasively using pulse wave analysis. Blood samples obtained pre- and post-treatments were analysed for erythrocyte antioxidant enzyme activity, plasma nitrite and malondialdehyde. In study 2 the effects of incremental cumulative doses (0.5, 1.0, 1.5 and 2.0 mg ml(-1) min(-1)) of intra-arterial ALA on forearm blood flow (FBF) were assessed in eight healthy subjects (aged 31 +/- 5 years) by conventional venous occlusion plethysmography. RESULTS: There were no significant changes on any of the central or peripheral haemodynamic measures after either oral or direct arterial administration of ALA. Plasma ALA was detected after oral supplementation (95% confidence intervals 463, 761 ng ml(-1)), but did not alter cellular or plasma measures of oxidative stress. CONCLUSIONS: Neither oral nor intra-arterial ALA had any effect on regional and systemic haemodynamics or measures of oxidative stress in healthy men.
Administration, Oral↗
Role of natriuretic peptides in regulation of conduit artery distensibility.
Arterial distensibility, assessed by the pulse-wave velocity (PWV), is an independent predictor of cardiovascular risk. We investigated whether natriuretic peptides, acting locally, modify conduit artery distensibility in vivo. All studies were conducted in anesthetized sheep (n = 18) by using a validated ovine hindlimb model. In brief, the PWV was calculated, with the use of the foot-to-foot methodology, from two pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Drugs were infused either proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath to control for any reflex changes in flow or sympathetic activation. First, the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were studied. Second, the role of endogenous ANP was investigated by infusing the natriuretic peptide receptor type A (NPRA)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPRC-selective agonist cANF was infused. Infusion of CNP or des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (cANF) had no effect on iliac PWV. However, infusion of ANP, and to a lesser degree BNP, resulted in a reduction in PWV (-9%; P < 0.01 and -6%; P < 0.05, respectively). A71915 increased iliac PWV from 2.97 +/- 0.13 to 3.06 +/- 0.13 m/s; P < 0.01. Coinfusion of A71915 with ANP completely abolished the effects of ANP (P < 0.01). Importantly, ANP-BNP infusion via the sheath did not alter PWV. In conclusion, ANP, and to a lesser extent BNP, modify large artery distensibility via the NPRA receptor. Neither CNP nor cANF altered PWV, suggesting that the NPRB and NPRC receptors do not acutely influence distensibility in vivo.
Animals↗
Rapid nongenomic aldosterone effects in the human forearm?
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Aldosterone↗
Vitamin C in heart failure: hype or hope?
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Antioxidants↗
Endothelin-1 regulates arterial pulse wave velocity in vivo.
OBJECTIVES: The aim of this study was to investigate whether endothelin-1, acting locally, regulates arterial distensibility, assessed by measuring pulse-wave velocity in vivo. BACKGROUND: Arterial stiffness is a key determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. However, the role of endothelin-1 (ET-1) in the regulation of arterial stiffness has not been investigated. METHODS: All studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated using the foot-to-foot methodology from two pressure waveforms simultaneously recorded with a high-fidelity, dual pressure-sensing catheter placed in the common iliac artery. RESULTS: Intra-arterial infusion of ET-1 significantly increased iliac PWV by 12 +/- 5% (mean +/- STD; p < 0.001), whereas infusion of the endothelin-A (ET(A)) receptor antagonist BQ-123 significantly reduced PWV by 12 +/- 4% (p < 0.001). After BQ-123 infusion, exogenously infused ET-1 did not significantly change PWV compared with infusion of saline (change of -0.08 +/- 0.11% vs. -0.01 +/- 0.07%; p = 0.53). Importantly, infusion of BQ-123 or ET-1 distal to the common iliac artery did not affect PWV. CONCLUSIONS: These results demonstrate, for the first time, that endogenous ET-1 production directly regulates large artery PWV in vivo. In addition, exogenous ET-1 increases PWV, and this can be blunted by ET(A) receptor blockade. These observations explain, in part, why conditions that exhibit up-regulation of ET-1 are also associated with arterial stiffening. Therefore, drugs that block ET(A) receptors may be effective in reducing large artery stiffness in humans, and thus cardiovascular risk.
Animals↗
Atrial natriuretic peptide regulates regional vascular volume and venous tone in humans.
OBJECTIVE: To date, the contribution of basal atrial natriuretic peptide (ANP) levels to resting vascular function in humans is unknown. In the present study we sought to investigate the role of ANP in regulating regional vascular volume and venous tone in healthy subjects. METHODS AND RESULTS: We used radionuclide plethysmography to examine the effects of ANP and the ANP-receptor antagonist A71915 on forearm vascular volume. Creating pressure/volume relations, we determined changes in vascular volume, compliance, and tone. Performing dose-ranging studies, we additionally assessed the potency and specificity of A71915 in the forearm resistance vasculature. Equilibrium blood pool scintigraphy was then used to assess the effects of systemic administration of A71915 on regional intestinal vascular volume. Infusion of ANP increased forearm vascular volume in a dose-dependent manner (maximum 20%; P<0.001), exerting a maximum venodilating effect at plasma levels similar to that seen in heart failure. A71915 increased venous tone, thereby decreasing vascular volume by 9.6+/-1.1%, P<0.001 (forearm), and 2.6+/-0.5%, P=0.01 (intestinal beds). At an infusion ratio of 50:1, A71915 almost completely abolished the effects of ANP on forearm blood flow. CONCLUSIONS: ANP locally regulates regional vascular volume and tone without affecting compliance.
Adult↗
Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure.
Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 +/- 3.1, 12.5 +/- 4.9 and 21.7 +/- 9.1 mmHg/ms respectively; P < 0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 +/- 4.1 mmHg/ms; P < 0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.
Administration, Oral↗
Modulation of the natriuretic peptide system in heart failure: from bench to bedside?
Since the discovery of atrial natriuretic peptide, the unravelling of the natriuretic peptide system has been a story of scientific success. However, bridging the gap between bench and bedside has proved difficult, and as yet has not provided any major clinical progress. In this review we will first give a detailed outline of the key elements constituting the natriuretic peptide system. Secondly, we will briefly explain the underlying rationale, basic concepts and evidence behind currently pursued strategies to potentiate the natriuretic peptide system. Thirdly, we will highlight some of the problems that have so far hindered successful translation of these theoretically viable treatment options into tangible clinical progress.
Animals↗
Supine rest reduces platelet activation and aggregation.
Platelet activation and aggregation are central processes in acute coronary syndromes and myocardial infarction, and are stimulated by physical and mental stress. However, it is not known if and to what extent the "ordinary" stress inherent in a person's daily routine contributes to platelet activation and aggregation. We measured platelet activation and aggregation in 12 healthy non-smokers, before and after 45 min supine rest in a calm environment. This simple manouver resulted in a highly significant fall in platelet aggregation (7.9-4.4 ohms, p<0.001) and in plasma epinephrine (35.6-22.5 ng/ml, p = 0.037), norepinephrine (392.8-202.7 ng/ml, p<0.001) and soluble P-selectin (51.9-44.7 ng/ml, p<0.001). Von Willebrand factor (86.2-80.9 IU/ml) and beta-thromboglobulin (279.1-262.4 IU/ml) did not change significantly. Our findings show that a person's ordinary daily routine contributes to platelet activation and aggregation, and that these can be reduced by supine rest. This has methodological implications for studies involving measures of platelet activation and aggregation, and also suggests a mechanism by which bed rest in a calm environment may contribute, however slightly, to the management of acute coronary syndromes.
Biomarkers↗
Inhibition of platelet aggregation by nitric oxide donors improves with rest.
It has been suggested that the platelets of patients with acute coronary syndromes (ACS) exist in a more activated state than those of patients with stable coronary heart disease (CHD) or healthy individuals. "Platelet nitrate responsiveness" (PNR) has been suggested as a measure of platelet activation, and has been shown to be reduced in both ACS and stable CHD. We examined the effect of a short period of undisturbed supine rest, an intervention aimed at reducing levels of "stress", on PNR. In 8 healthy subjects we found that 45 minutes of rest led to a highly significant reduction in platelet aggregation and increase in PNR. Our finding supports the hypothesis that stress contributes to platelet activation as reflected in reduced PNR, which may contribute to the link between acute stress and cardiovascular events. It also emphasises that standardisation of sampling conditions in vitally important in studies utilizing PNR.
Blood Platelets↗
No evidence for persistence of multidrug-resistant viral strains after a 7-month treatment interruption in an HIV-1-infected individual.
The number of HIV-1-infected patients harboring multidrug-resistant viruses is increasing. Since new antiretroviral drugs with favorable resistance profiles are limited, innovative strategies are urgently needed. Treatment interruptions can lead to a loss in HIV resistance followed by improved response to reinitiated therapy. The authors report the case of a patient with sustained antiretroviral response for 3.5 years after a 7-month treatment interruption. Concomitant with an increase in replication capacity, multidrug-resistant viruses gradually disappeared during treatment interruption. Resistance to protease inhibitors (PI) was completely lost, and resistance to reverse transcriptase inhibitors was still present when therapy was reinitiated. PI-resistant variants were not detected at four time points after treatment reinitiation. The alignment of the nucleic acid sequences from all different time points suggested that the viruses obtained after treatment reinitiation evolved from less-resistant variants prior to treatment interruption. This was supported by in vitro propagation of the viral plasma population and an individual clone derived from the time point of treatment interruption. This is consistent with a model favoring reversible binding of HIV-1 to reservoirs, as has recently been proposed for follicular dendritic cells. Understanding of this process could help to exploit the reduced fitness of drug-resistant viruses for treatment interruptions.
Adult↗
Assessment of venous capacitance. Radionuclide plethysmography: methodology and research applications.
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Arteries↗
Lack of rapid aldosterone effects on forearm resistance vasculature in health.
OBJECTIVES: Systemic infusions of aldosterone cause an acute increase in systemic vascular resistance (SVR) in healthy subjects. It is not clear whether this is due to a direct effect on the vasculature or the result of increased sympathetic tone. We investigated the short-term effects of locally infused aldosterone on the forearm resistance bed. METHODS: In this dose response study, we assessed the effects of incremental doses (10, 50, 100 ng/minute) of intrabrachial aldosterone on forearm blood flow (FBF), using conventional strain gauge plethysmography. Arterial blood pressure was monitored continuously, using finger photo- plethysmography. Forearm vascular resistance (FVR) was calculated. FBF and FVR were also measured in the non-infused arm. Changes in FBF and FVR in the infused arm were corrected for those occurring in the control arm. RESULTS: Plasma aldosterone levels in the venous effluent of the infused arm increased in a dose-dependent fashion, from 113.3+/-17.9 pg/ml at baseline to 297.8+/-51.8 pg/ml at 10 ng/minute (p=<0.01), 743.9+/-105.9 pg/ml at 50 ng/min (p=<0.001 vs. baseline) and 1230.6+/-73.7 pg/ml at 100 ng/min (p=<0.0005 vs. baseline). Plasma concentrations of aldosterone in the control arm did not change significantly vs. baseline. The corrected FBF (+4.1+/-10.3%) and corrected FVR (+4.3+/-11.3%) did not change significantly even at peak infusion rates. CONCLUSIONS: Local intra-arterial infusion of aldosterone had no acute effect on forearm resistance vessels in healthy male volunteers.
Adult↗