3-methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene, has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atria and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current IKr (EC50=0.25 μM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca2+ current (ICa) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (EC50=4.7 μM) of the sodium current (INa), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atria measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.<br/

Cardinality of the Ryser Classes and the Motzkin Paths with Weights

Рассматривается задача о вычислении мощности классов квадратных матриц, состоящих из ну- лей и единиц, с фиксированным значением строчных и столбцевых сумм. Получено рекуррентное соотношение, позволяющее вычислить мощность данных классов и устанавливающее связь этой задачи с вопросами о перечислении взвешенных путей Моцкина. Приведены примеры использова- ния найденного соотношения.We consider the problem of computation of the cardinality of matrix classes with fixed row and column sums. We obtain a new recurrence formula for the cardinality of these classes which gives a connection between this problem and the Motzkin paths. Examples of using the obtained recurrence relation are furnished

Cardinality of the Ryser Classes and the Motzkin Paths with Weights

Рассматривается задача о вычислении мощности классов квадратных матриц, состоящих из ну- лей и единиц, с фиксированным значением строчных и столбцевых сумм. Получено рекуррентное соотношение, позволяющее вычислить мощность данных классов и устанавливающее связь этой задачи с вопросами о перечислении взвешенных путей Моцкина. Приведены примеры использова- ния найденного соотношения.We consider the problem of computation of the cardinality of matrix classes with fixed row and column sums. We obtain a new recurrence formula for the cardinality of these classes which gives a connection between this problem and the Motzkin paths. Examples of using the obtained recurrence relation are furnished

Effects of new antiarrhythmic agent SS-68 on excitation conduction, electrical activity in Purkinje fibers and pulmonary veins: Assessment of safety and side effects risk

The compound SS-68 has been selected among numerous new derivatives of indole and demonstrated antiarrhythmic effects in animal models. The present study concerns several aspects of SS-68 safety and efficacy as a potential antiarrhythmic drug. The first estimation of atrioventricular conduction in mammalian heart under SS-68 has been carried out; effects of SS-68 in Purkinje fibers and myocardium of pulmonary veins have been investigated. The drug weakly affects cardiac atrioventricular conduction: only high concentrations of SS-68 (≥10 μmol/L) significantly decrease this parameter. Also, the drug weakly affects Purkinje fibers automaticity, but effectively alters action potential waveform in Purkinje fibers in a concentration-dependent manner. SS-68 (0.1–100 μmol/L) failed to induce any early or delayed afterdepolarizations in Purkinje fibers both in basal conditions and under provocation of proarrhythmic activity by norepinephrine (NE). Moreover, 10 μmol/L SS-68 suppressed NE-induced extra-beats and rapid firing in Purkinje fibers. In pulmonary veins only high concentrations of SS-68 significantly increased action potential duration, while lower concentrations (0.1–1 μmol/L) were ineffective. Also, 0.1–100 μmol/L SS-68 was unable to elicit arrhythmogenic alternations of action potential waveform in pulmonary veins. In conclusion, SS-68 has no proarrhythmic effects, such as afterdepolarizations or abnormal automaticity in used experimental models