Carbon monoxide affects electrical and contractile activity of rat myocardium

<p>Abstract</p> <p>Background</p> <p>Carbon monoxide (CO) is a toxic gas, which also acts in the organism as a neurotransmitter. It is generated as a by-product of heme breakdown catalyzed by heme oxygenase. We have investigated changes in electrical and contractile activity of isolated rat atrial and ventricular myocardium preparations under the influence of CO.</p> <p>Methods</p> <p>Standard microelectrode technique was used for intracellular registration of electrical activity in isolated preparations of atrial and ventricular myocardium. Contractions of atrial myocardial stripes were registered via force transducer.</p> <p>Results</p> <p>CO (10^-4- 10^-3M) caused prominent decrease of action potential duration (APD) in working atrial myocardium as well as significant acceleration of sinus rhythm. In addition CO reduced force of contractions and other parameters of contractile activity. Inhibitor of heme oxygenase zinc protoporphyrin IX exerts opposite effects: prolongation of action potential, reduction of sinus rhythm rate and enhancement of contractile function. Therefore, endogenous CO, which may be generated in the heart due to the presence of active heme oxygenase, is likely to exert the same effects as exogenous CO applied to the perfusing medium. In ventricular myocardium preparations exogenous CO also induced shortening of action potential, while zinc protoporphyrin IX produced the opposite effect.</p> <p>Conclusions</p> <p>Thus, endogenous or exogenous carbon monoxide may act as an important regulator of electrical and contractile cardiac activity.</p

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/

Thermal acclimation and seasonal acclimatization: a comparative study of cardiac response to prolonged temperature change in shorthorn sculpin

Seasonal thermal remodelling (acclimatization) and laboratory thermal remodelling (acclimation) can induce different physiological changes in ectothermic animals. As global temperatures are changing at an increasing rate, there is urgency to understand the compensatory abilities of key organs such as the heart to adjust under natural conditions. Thus, the aim of the present study was to directly compare the acclimatization and acclimatory response within a single eurythermal fish species, the European shorthorn sculpin (Myoxocephalus scorpio). We used current- and voltage-clamp to measure ionic current densities in both isolated atrial and ventricular myocytes from three groups of fish: (1) summer-caught fish kept at 12°C (‘summer-acclimated’); (2) summer-caught fish kept at 3°C (‘cold acclimated’); and (3) fish caught in March (‘winter-acclimatized’). At a common test temperature of 7.5°C, action potential (AP) was shortened by both winter acclimatization and cold acclimation compared with summer acclimation; however, winter acclimatization caused a greater shortening than did cold acclimation. Shortening of AP was achieved mostly by a significant increase in repolarizing current density (IKr and IK1) following winter acclimatization, with cold acclimation having only minor effects. Compared with summer acclimation, the depolarizing L-type calcium current (ICa) was larger following winter acclimatization, but again, there was no effect of cold acclimation on ICa. Interestingly, the other depolarizing current, INa, was downregulated at low temperatures. Our further analysis shows that ionic current remodelling is primarily due to changes in ion channel density rather than current kinetics. In summary, acclimatization profoundly modified the electrical activity of the sculpin heart while acclimation to the same temperature for &gt;1.5 months produced very limited remodelling effects. © 2019. Published by The Company of Biologists Ltd.Russian Foundation for Basic Research, RFBR: 18-315-20049The study was supported by the Russian Foundation for Basic Research (18-315-20049 to D.V.A.)

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