Biomedical subjects

Joachim Winter

Publications and source records attributed to Joachim Winter.

3 recordsLinked to original sources

PubMed2003

Long-term follow-up of sudden cardiac arrest survivors and electrophysiologically guided antiarrhythmic therapy.

Sudden cardiac arrest survivors have a high risk of suffering from recurrent arrhythmic events. Recent studies have shown that these patients have a significantly decreased mortality rate, if they are supplied with an implantable cardioverter/defibrillator (ICD). The aim of this study was to evaluate the long-term prognosis of patients with electrophysiologically guided antiarrhythmic drug therapy in comparison to patients with ICD. 204 consecutive survivors of sudden cardiac arrest were enrolled in this study. All patients were examined with an initial electrophysiologic study (EPS) with programmed ventricular stimulation. Patients were treated with antiarrhythmic drugs (if the inducible tachycardia was suppressed) or with the implantation of an ICD. The maximal follow-up period was 120 months, the mean period was 53.3 +/- 31.4 months (ICD) versus 60.3 +/- 35.5 months (EPS, nonsignificant). Patients with ICD showed an overall mortality rate of 14.6%, whereas EPS-guided patients had a mortality rate of 43.2% (p < 0.001). The cardiac and arrhythmogenic mortality rates were significantly lower in the ICD group (12 vs. 43%, p < 0.01, and 1 vs. 16%, p < 0.001, respectively). A reduction of the mortality risk was observed in the ICD group by up to 61% (all-cause mortality), 52% (cardiac mortality) and 97.2% (arrhythmogenic mortality). In arrhythmic event survivors with ICD, arrhythmic and overall mortality rates are significantly lower compared to patients with an EPS-guided drug therapy. In the secondary prevention of sudden cardiac death, ICD should be the first choice of antiarrhythmic therapy.

Adult↗

PubMed2002

Rotation of the exo-methylene group of (R)-3-methylitaconate catalyzed by coenzyme B(12)-dependent 2-methyleneglutarate mutase from Eubacterium barkeri.

2-Methyleneglutarate mutase from the anaerobe Eubacterium (Clostridium) barkeri is an adenosylcobalamin (coenzyme B(12))-dependent enzyme that catalyzes the equilibration of 2-methyleneglutarate with (R)-3-methylitaconate. Two possibilities for the mechanism of the carbon skeleton rearrangement of the substrate-derived radical to the product-related radical are considered. In both mechanisms an acrylate group migrates from C-3 of 2-methyleneglutarate to C-4. In the "addition-elimination" mechanism this 1,2-shift occurs via an intermediate, a 1-methylenecyclopropane-1,2-dicarboxylate radical, in which the migrating acrylate is simultaneously attached to both C-3 and C-4. In the "fragmentation-recombination" mechanism the migrating group, a 2-acrylyl radical, becomes detached from C-3 before it starts bonding to C-4. In an attempt to distinguish between these two possibilities we have investigated the action of 2-methyleneglutarate mutase on the stereospecifically deuterated substrates (Z)-3-methyl[2'-(2)H(1)]itaconate and (Z)-3-[2'-(2)H(1),methyl-(2)H(3)]methylitaconate. The enzyme catalyzes the equilibration of both compounds with their corresponding E-isomers and with a 1:1 mixture of the corresponding (E)- and (Z)-2-methylene[2'-(2)H(1)]glutarates, as shown by monitoring of the reactions with (1)H and (2)H NMR. In the initial phase of the enzyme-catalyzed equilibration a significant excess (8-11%) of (E)-3-methyl[2'-(2)H(1)]itaconate over its equilibrium value was observed ("E-overshoot"). The E-overshoot was only 3-4% with (Z)-3-[2'-(2)H(1),methyl-(2)H(3)]methylitaconate because the presence of the deuterated methyl group raises the energy barrier from 3-methylitaconate to the corresponding radical. The overshoot is explained by postulating that the migrating acrylate group has to overcome an additional energy barrier from the state leading back to the substrate-derived radical to the state leading forward to the product-related radical. It is concluded that the fragmentation-recombination mechanism can provide an explanation for the results in terms of an additional energy barrier, despite the higher calculated activation energy for this pathway.

Catalysis↗

PubMed2002

[The isolated rabbit heart: comparison between five different modifications].

BACKGROUND: The isolated heart as an experimental model has been firmly established for more than 100 years. MATERIAL AND METHODS: In this study, five modifications are compared: 1. modified Langendorff apparatus (LA) with modified Krebs-Henseleit (KH) solution a) not containing bovine serum albumin (BSA; n = 13) and b) containing BSA (n = 16), 2. LA with KH solution containing BSH and bovine erythrocytes (n = 14), 3. LA with support rabbit (n = 6), and 4. "working heart" preparation with KH solution, BSA and bovine erythrocytes (n = 16). In the latter modification, no balloon was inserted into the left ventricular cavity, i. e., systemic and coronary circuits were not separated from each other. After completion of the preparation and 20-min stabilization, hemodynamic and metabolic data were assessed while the hearts were contracting in the ejecting mode. Thereafter, protocols for different studies were performed that are not presented here. However, the stability of the modifications within their individual protocols is reported. RESULTS: The results suggest that hearts perfused with KH solution are well suited for short protocols. In spite of the additional costs and time, blood perfusion is required for long-lasting protocols or if changes in coronary flow are to be investigated. CONCLUSIONS: The working heart exhibits both the best function and stability at a relatively low experimental expenditure. Yet, it is not suited for studies where perfusion pressure needs to be changed independent of arterial pressure.

Animals↗