Peter Musil

Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function

The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol‐induced HF.

Circulating MicroRNAs as Potential Biomarkers of Exercise Response

Systematic physical activity increases physical fitness and exercise capacity that lead to the improvement of health status and athletic performance. Considerable effort is devoted to identifying new biomarkers capable of evaluating exercise performance capacity and progress in training, early detection of overtraining, and monitoring health-related adaptation changes. Recent advances in OMICS technologies have opened new opportunities in the detection of genetic, epigenetic and transcriptomic biomarkers. Very promising are mainly small non-coding microRNAs (miRNAs). miRNAs post-transcriptionally regulate gene expression by binding to mRNA and causing its degradation or inhibiting translation. A growing body of evidence suggests that miRNAs affect many processes and play a crucial role not only in cell differentiation, proliferation and apoptosis, but also affect extracellular matrix composition and maintaining processes of homeostasis. A number of studies have shown changes in distribution profiles of circulating miRNAs (c-miRNAs) associated with various diseases and disorders as well as in samples taken under physiological conditions such as pregnancy or physical exercise. This overview aims to summarize the current knowledge related to the response of blood c-miRNAs profiles to different modes of exercise and to highlight their potential application as a novel class of biomarkers of physical performance capacity and training adaptation.

Pycnogenol® improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats

We studied whether Pycnogenol® (PYC) may attenuate the development of experimental streptozotocin‐induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)‐producing molecules (gp91phox‐containing NADPH oxidase and NO‐signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha‐tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS‐producing enzymes and cytoskeletal components. Copyright

Glucose and blood pressure lowering effects of Pycnogenol ® are inefficient to prevent prolongation of QT interval in experimental diabetic cardiomyopathy

Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark - Pycnogenol(®) (PYC) with hypoglycaemic and antioxidant properties in 8-9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50 mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p<0.05) and significantly increased mean arterial blood pressure (by 19%; p<0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p<0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p<0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p<0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.

Assembly of a polymer lab-on-chip device for impedimetric measurements of D-dimers in whole blood

This paper reports the development and characterisation of an assembly technology for a polymer lab-on-chip. The system consists of a 150 μm deep hot embossed microfluidic channel in polycarbonate and Au electrodes fabricated separately by photolithography on polyethylenenaphthalate. The system is designed for impedimetric immunoassay detection in whole blood. Electrode layer and microfluidic substrate are joined by means of a 50 μm thick double-sided medical grade adhesive tape, adjusted with an optical alignment system. The bond proved to be liquid tight at room temperature. An alignment accuracy of 34 μm (+/- 19 μm) evaluated over a set of 23 samples, was achieved. The effect of alignment accuracy of the intermediate adhesive film on whole blood flow properties in the device is studied. Already an alignment error of 70 μm increases the flushing out time of whole blood by approximately 20%.