Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA-supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase- and CYP-dependent pathways. Raising the Omega-3 Index from about 4 to 8 primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived lipoxygenase-dependent monohydroxy-metabolites including the precursors of resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA-supplementation

Cardiac magnetic field mapping quantified by Kullback-Leibler entropy detects patients with coronary artery disease

Cardiac magnetic field mapping (CMFM) is a noninvasive method to determine cardiac electrical activity. We analysed the utility of CMFM for the detection of patients with coronary artery disease (CAD) without subjecting them to stress. We studied 59 healthy control subjects and 101 patients with CAD without previous myocardial infarction (MI). The heart's magnetic field was recorded over the anterior chest wall using a multichannel magnetic measurement system with axial second-order gradiometers. The evaluation of CMFM was based on comparison of the 'ideal' group mean maps of young healthy subjects and maps of examined individuals. Three measures of similarity were considered: Kullback-Leibler (KL) entropy, normalized residual magnetic field strength and deviations in the magnetic field map orientation. The mean values of these parameters during the depolarization and repolarization were used for further classification with the help of logistic regression. The feature set based on the KL-entropy demonstrated the best classification results (sensitivity/specificity of 85/80%), followed by the residual feature (85/75%) and the magnetic field orientation feature (80/73%) sets. The forward stepwise technique was applied to select the best set of features from the combined feature set. Two parameters were selected, namely the KL-entropy for the repolarization period and the residual parameter for the depolarization period. The classification based on these parameters demonstrated a sensitivity of 88% and a specificity of 88% for the distinction of CAD patients from the control subjects. The area under the receiver operator curve was 94%. Hence, we suggest that CMFM evaluation based on KL-entropy is a promising technique to identify patients with CAD

Operation of high-temperature superconductor magnetometer with submicrometer bicrystal junctions

We investigated the noise properties of dc superconducting quantum interference device flip-chip magnetometers with submicrometer-wide bicrystal junctions operating at 77.4 K. The noise of the magnetometers with electronics was about 6 fT/rootHz at frequencies above 100 Hz increasing up to about 20 fT/rootHz at 1 Hz. The operation of the magnetometers was characterized in an electronic axial first order gradiometer system, which was employed for biomagnetic measurements. The system demonstrated a gradient resolution of about 1 fT/cmrootHz at 77.4 K and stable operation in a standard magnetically shielded room under clinical conditions. (C) 2002 American Institute of Physics

Cardiac magnetic resonance and cardiac magnetic field mapping in a patient with stress-induced cardiomyopathy (tako-tsubo)

We encountered a 65-year-old woman with typical electrocardiogram (ECG) changes and new-onset left ventricular dysfunction with apical ballooning that exhibited typical changes of tako-tsubo-like cardiomyopathy. We used cardiac magnetic resonance (CMR) and cardiac magnetic field mapping (CMFM) to detect changes in structural, mechanical, and electrophysiological myocardial properties during follow-up. CMR displayed an acute myocardial injury, but neither fibrosis nor necrosis. CMFM exhibited severely disturbed repolarization with an inhomogeneous magnetic field. These pathological findings persisted much longer than the abnormalities detected by CMR and the ECG

Time course of changes in cardiac magnetic field mapping after myocardial infarction in rats

Noninvasive electrophysiological phenotyping in small rodents is usually done by ECG studies. However information content from few ECG leads is limited. We investigated how Cardiac Magnetic Field Mapping (CMFM) parameters change at different time points after myocardial infarction in rats. Therefore, myocardial infarction was induced by ligation of the anterior descending artery in male Sprague Dawley (SD) rats. CMFM recordings were done using a 7 channel SQUID system during a follow up of 4 weeks after myocardial infarction. Rats with myocardial infarction were compared with sham operated animals. Anterior myocardial infarction resulted in a significant reduction in left ventricular function and initiation of structural remodeling process. Acute myocardial infarction was associated with pronounced changes in STT segment, including elevation of magnetic field strengths and a rotation of the magnetic field orientation. CMFMs obtained within the chronic phase of myocardial infarction revealed signs of electrical remodeling by prolongation of repolarization parameters and increase in inhomogeneity of repolarization. Another characteristic finding was a progressive loss in MCG RPeak values. CMFM noninvasively detects electrophysiological changes in rats with myocardial infarction. Different alterations characterized acute ischemia and electrical remodeling, which accompanied structural remodeling in the chronic state of the disease

Investigation of an automatic sleep stage classification by means of multiscorer hypnogram

OBJECTIVES: Scoring sleep visually based on polysomnography is an important but time-consuming element of sleep medicine. Whereas computer software assists human experts in the assignment of sleep stages to polysomnogram epochs, their performance is usually insufficient. This study evaluates the possibility to fully automatize sleep staging considering the reliability of the sleep stages available from human expert sleep scorers. METHODS: We obtain features from EEG, ECG and respiratory signals of polysomnograms from ten healthy subjects. Using the sleep stages provided by three human experts, we evaluate the performance of linear discriminant analysis on the entire polysomnogram and only on epochs where the three experts agree in their sleep stage scoring. RESULTS: We show that in polysomnogram intervals, to which all three scorers assign the same sleep stage, our algorithm achieves 90% accuracy. This high rate of agreement with the human experts is accomplished with only a small set of three frequency features from the EEG. We increase the performance to 93% by including ECG and respiration features. In contrast, on intervals of ambiguous sleep stage, the sleep stage classification obtained from our algorithm, agrees with the human consensus scorer in approximately 61%. CONCLUSIONS: These findings suggest that machine classification is highly consistent with human sleep staging and that error in the algorithm's assignments is rather a problem of lack of well-defined criteria for human experts to judge certain polysomnogram epochs than an insufficiency of computational procedures