Perioperative Strategien zur Regulierung des Sympathikotonus

Zusammenfassung: Obwohl für verschiedene therapeutische Konzepte zur Verminderung der kardialen perioperativen Morbidität und Mortalität zunehmend Evidenz vorliegt, bleibt die tatsächliche Umsetzung solcher Konzepte im klinischen Alltag oft aus. Zwar ist einem großen Teil der klinisch tätigen Ärzte die wachsende Literatur bekannt; dieses Wissen wird aber nur in einem Teil der Fälle angewendet, selbst wenn allgemein akzeptierte Indikationen bestehen. Die vorliegende Übersichtsarbeit hat deshalb zum Ziel, die Gründe für die mangelnde Umsetzung aufzuzeigen und nochmals die wesentlichen Grundlagen sowie die klinische Bedeutung einzelner Strategien einschließlich des α2-Agonismus, der β-adrenergen Blockade und der Regionalanästhesien zusammenzufassen. Dies insbesondere im Hinblick auf die klinische Anwendung dieser Konzepte in einem allgemeinanästhesiologischen Umfeld. Zudem wird ein Ausblick in die auf "gene profiling" basierende individualisierte Pharmakotherapie der perioperativen Medizin von morgen gegebe

Anaesthetics and cardiac preconditioning. Part II. Clinical implications

There is compelling evidence that preconditioning occurs in humans. Experimental studies with potential clinical implications as well as clinical studies evaluating ischaemic, pharmacological and anaesthetic cardiac preconditioning in the perioperative setting are reviewed. These studies reveal promising results. However, there are conflicting reports on the efficacy of preconditioning in the diseased and aged myocardium. In addition, many anaesthetics and a significant number of perioperatively administered drugs affect the activity of cardiac sarcolemmal and mitochondrial KATP channels, the end‐effectors of cardiac preconditioning, and thereby markedly modulate preconditioning effects in myocardial tissue. Although these modulatory effects on KATP channels have been investigated almost exclusively in laboratory investigations, they may have potential implications in clinical medicine. Important questions regarding the clinical utility and applicability of perioperative cardiac preconditioning remain unresolved and need more experimental work and randomized controlled clinical trials. Br J Anaesth 2003; 91: 566-7

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists

Objectives: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. Methods: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. Results: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. Conclusions: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulu

Suppression of the 1 MHz beam current modulation in the LEDA/CRITS proton source

Earlier operation of a microwave proton source exhibited an approximate 1-MHz modulation in the beam current. This oscillation could cause instabilities at higher energies in the linac, as the low-level RF control for linac operation rolls off at 200 kHz. Tests on a dummy load show the modulation is created by the magnetron itself: at a typical power level required for the source operation (680W), the 1-MHz sideband level was as high as {minus}4 dB from carrier. Since the magnetron exhibited better behavior at higher levels, a RF power attenuator is inserted to force the magnetron to run at a 50% higher power level for the same final power in the load. This attenuator is made of two antennas plunged in the waveguide and connected to dummy loads by a coaxial line. As the antenna are separated by a quarter of the guided wavelength, mismatching effects approximately cancel each other. The antenna length is experimentally adjusted to obtain the {minus}1.8 dB attenuation required. Magnetron operation at the higher power level gives a beam current spectrum free of the 1-MHz modulation, showing the coherent beam noise is not generated by plasma chamber phenomena

Persistence of pharmaceutical compounds and other organic wastewater contaminants in a conventional drinking-water-treatment plant

In a study conducted by the US Geological Survey and the Centers for Disease Control and Prevention, 24 water samples were collected at selected locations within a drinking-water-treatment (DWT) facility and from the two streams that serve the facility to evaluate the potential for wastewater-related organic contaminants to survive a conventional treatment process and persist in potable-water supplies. Stream-water samples as well as samples of raw, settled, filtered, and finished water were collected during low-flow conditions, when the discharge of effluent from upstream municipal sewage-treatment plants accounted for 37–67% of flow in stream 1 and 10–20% of flow in stream 2. Each sample was analyzed for 106 organic wastewater-related contaminants (OWCs) that represent a diverse group of extensively used chemicals.Forty OWCs were detected in one or more samples of stream water or raw-water supplies in the treatment plant; 34 were detected in more than 10% of these samples. Several of these compounds also were frequently detected in samples of finished water; these compounds include selected prescription and non-prescription drugs and their metabolites, fragrance compounds, flame retardants and plasticizers, cosmetic compounds, and a solvent. The detection of these compounds suggests that they resist removal through conventional water-treatment processes. Other compounds that also were frequently detected in samples of stream water and rawwater supplies were not detected in samples of finished water; these include selected prescription and non-prescription drugs and their metabolites, disinfectants, detergent metabolites, and plant and animal steroids. The non-detection of these compounds indicates that their concentrations are reduced to levels less than analytical detection limits or that they are transformed to degradates through conventional DWT processes. Concentrations of OWCs detected in finished water generally were low and did not exceed Federal drinking-water standards or lifetime health advisories, although such standards or advisories have not been established for most of these compounds. Also, at least 11 and as many as 17 OWCs were detected in samples of finished water. Drinking-water criteria currently are based on the toxicity of individual compounds and not combinations of compounds. Little is known about potential human-health effects associated with chronic exposure to trace levels of multiple OWCs through routes such as drinking water. The occurrence in drinking-water supplies of many of the OWCs analyzed for during this study is unregulated and most of these compounds have not been routinely monitored for in the Nation’s source- or potable-water supplies. This study provides the first documentation that many of these compounds can survive conventional water-treatment processes and occur in potable-water supplies. It thereby provides information that can be used in setting research and regulatory priorities and in designing future monitoring programs. The results of this study also indicate that improvements in water-treatment processes may benefit from consideration of the response of OWCs and other trace organic contaminants to specific physical and chemical treatments

Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway

OBJECTIVE: We tested whether ischemic postconditioning (IPostC) is protective in remodeled myocardium. METHODS: Post-myocardial infarct (MI)-remodeled hearts after permanent coronary artery ligation and one kidney one clip (1K1C) hypertensive hearts of male Wistar rats were exposed to 40 min of ischemia followed by 90 min of reperfusion. IPostC was induced by six cycles of 10 s reperfusion interspersed by 10 s of no-flow ischemia. Activation of reperfusion injury salvage kinases was measured using Western blotting and in vitro kinase activity assays. RESULTS: IPostC prevented myocardial damage in both MI-remodeled and 1K1C hearts, as measured by decreased infarct size and lactate dehydrogenase release, and improved function. The reduction in infarct size and the recovery of left ventricular contractility achieved by IPostC was less in 1K1C hearts, but was unchanged in MI-remodeled hearts when compared to healthy hearts. In contrast, the recovery of inotropy was unaffected in 1K1C hearts, but was less in MI-remodeled hearts. Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway with LY294002 abolished the protective effects of IPostC on both disease models and healthy hearts. Western blot analysis in conjunction with in vitro kinase activity assays identified protein kinase B (PKB)/Akt but not p42/p44 extracellular-signal regulated kinase 1/2 (ERK1/2) as the predominant kinase in IPostC-mediated cardioprotection in remodeled hearts. IPostC increased phosphorylation of the PKB/Akt downstream targets eNOS, GSK3beta, and p70S6K in remodeled hearts. CONCLUSION: Our results offer evidence that IPostC mediates cardioprotection in the remodeled rat myocardium primarily via activation of the PI3K-PKB/Akt reperfusion injury salvage kinase pathwa

Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery

Background. Cardiac preconditioning is thought to be involved in the observed decreased coronary artery reocclusion rate in patients with angina preceding myocardial infarction. We prospectively examined whether preconditioning by sevoflurane would decrease late cardiac events in patients undergoing coronary artery bypass graft (CABG) surgery. Methods. Seventy-two patients scheduled for elective CABG surgery were randomized to preconditioning by sevoflurane (10 min at 4 vol%) or placebo. For all patients, follow-up of adverse cardiac events was obtained 6 and 12 months after surgery. Transcript levels for platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31), catalase and heat shock protein 70 (Hsp70) were determined in atrial biopsies after sevoflurane preconditioning. Results. Pharmacological preconditioning by sevoflurane reduced the incidence of late cardiac events during the first year after CABG surgery (sevoflurane 3% vs 17% in the placebo group, log-rank test, P=0.038). One patient in the sevoflurane group and three patients in the placebo group experienced new episodes of congestive heart failure and three additional patients had coronary artery reocclusion. Perioperative peak concentrations for myocardial injury markers were higher in patients with subsequent late cardiac events [NTproBNP, 9031 (4125) vs 3049 (1906) ng litre−1, P<0.001; cTnT, 1.31 (0.88) vs 0.46 (0.29) µg litre−1, P<0.001]. Transcript levels were reduced for PECAM-1 and increased for catalase but unchanged for Hsp70 in atrial biopsies after sevoflurane preconditioning. Conclusions. This prospective randomized clinical study provides evidence of a protective role for pharmacological preconditioning by sevoflurane in late cardiac events in CABG patients, which may be related to favourable transcriptional changes in pro- and antiprotective protein