Biomedical subjects

J Weckmüller

Publications and source records attributed to J Weckmüller.

4 recordsLinked to original sources

PubMed2002

[Rate-responsive pacemaker concept: parametric system identification].

The focus of this paper is the design of a rate-responsive pacemaker which uses the atrio-ventricular conduction time (AVCT) as an exertion related sensor signal. AVCT can be easily obtained from an intracardial electrogram. During atrial pacing AVCT shortens with exercise but increases with the stimulation rate. Hence, an AVCT based pacemaker always establishes a closed-loop system. General design rules for an AVCT pacemaker have been developed from our experimental results and a system-theoretical treatment. Topics addressed were the controller gain, uncertainties concerning the dynamics of the AVCT, the attenuation of disturbances, the closed-loop bandwidth and stability.

Algorithms↗

PubMed2001

Oxidative stress increases endothelin-1 synthesis in human coronary artery smooth muscle cells.

Endothelins, nitric oxide, and oxygen-derived free radicals decisively regulate vascular tone. An imbalance in the biosynthesis of these substances in pathophysiologic conditions may trigger vasospasm and promote the development of atherosclerosis. Previous studies have shown that oxygen-derived free radicals can increase the synthesis of endothelin-1 in cultured endothelial cells. Interestingly, conditions of increased oxidative stress within smooth muscle cells as induced by angiotensin II infusion or hypercholesterolemia have been shown to be associated with increased autocrine synthesis of endothelin-1. Because endothelin-1 formed in smooth muscle cells can trigger hypersensitivity to vasoconstrictors, we tested whether oxidative stress per se may affect endothelin expression in vascular smooth muscle cells. Cultured human coronary artery smooth muscle cells were exposed to oxidative stress generated by the xanthine/xanthine oxidase reaction or by hydrogen peroxide. Preproendothelin-1 mRNA content was quantitated by means of quantitative polymerase chain reaction and endothelin-1 protein was measured by radioimmunoassay. Incubation with xanthine/xanthine oxidase significantly increased preproendothelin-1 mRNA synthesis, whereas GAPDH remained unchanged. Likewise, xanthine/xanthine oxidase also led to a dose-dependent increase of intracellular endothelin-1. The increase in ET-1 expression induced by xanthine/xanthine oxidase was significantly inhibited by superoxide dismutase but not by catalase. We conclude that oxygen-derived free radicals can stimulate the synthesis of endothelin-1 in endothelial and vascular smooth muscle cells by increasing preproendothelin-1 mRNA content and that this effect is mediated predominantly by superoxide anions. We therefore have identified a new mechanism in the interaction of oxidative stress and endothelin-1 expression in smooth muscle cells that may have important implications in diseases such as atherosclerosis and hypertension.

Cells, Cultured↗

PubMed2000

Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter.

Modulation of the biosynthesis of the vasoconstrictor peptide endothelin-1 by oxygen-derived free radicals generated by xanthine oxidase or hydrogen peroxide was studied in cultured endothelial cells. Endothelin-1 metabolism was investigated at the level of endothelin-1 promoter, preproendothelin-1 mRNA and intracellular big endothelin-1. Endothelin-1 mRNA, as characterized by Northern blotting, was increased both time- and dose-dependently by xanthine oxidase to up to 500% above baseline. Analysis of endothelin-1 promoter activity using a construct containing 1329 bp of the endothelin-1 promoter revealed that promoter activity was increased up to eight-fold by incubation with xanthine oxidase. Specificity was ascertained by co-incubation with superoxide dismutase and catalase leading to inhibition of the effect of xanthine oxidase. A significant contribution of nitric oxide was ruled out, since NOS III-mRNA transcription remained unchanged and l -NAME did not significantly alter endothelin-1 promoter activity. Synthesis of intracellular big endothelin-1 protein was increased dose-dependently by xanthine oxidase. Our results indicate that oxidative stress leads to increased endothelial synthesis of big endothelin-1, which is a previously unknown mechanism and may help to understand the detrimental association of increased oxidative stress and elevated endothelin-1 levels in pathophysiological conditions promoting atherosclerosis.

Animals↗

PubMed1999

Coronary angioplasty in octogenarians. Quality of life and costs.

BACKGROUND: Improvement in quality of life is the major motivation for angioplasty in very elderly patients. The alleviation of symptoms with this method is therefore of particular interest. However, little is known about the impact of angioplasty in terms of quality of life in octogenarian patients and what the treatment costs are. METHODS AND RESULTS: We prospectively compared patients aged 80 years or above (n=34, 83+/-3 years) with younger patients (n=34, 62+/-8 years) regarding their quality of life following coronary angioplasty. Patients were interviewed immediately following angioplasty and 6 months later using the SF-36 health survey. Key determinants of costs and follow-up for 6 months were documented. The number of diseased vessels, interventions performed and number of lesions treated were comparable in both groups. Success rates were lower in the octogenarian than in the control group (88 vs 97%). In both groups angioplasty significantly improved the ability to fulfil physical role expectations and decreased bodily pain. Both the effects on Role Physical and on Bodily Pain were more pronounced in the octogenarian patients. Determinants of costs did not differ significantly between the two groups. CONCLUSIONS: Our data demonstrate that in octogenarians with symptomatic coronary heart disease, coronary angioplasty significantly increases physical abilities and decreases pain. Further, these effects were more pronounced in octogenarian patients than in younger patients.

Aged↗