Effects of Ranolazine and Ivabradine on Pulmonary Microhemodynamics in Experimental Model of Pulmonary Thromboembolism.

We studied changes of pulmonary microhemodynamics when modeling pulmonary artery thromboembolism on perfused isolated rabbit lungs after pretreatment with ranolazine and ivabradine. The increase in pulmonary artery pressure, pulmonary vascular resistance, and pre- and postcapillary resistance was less pronounced than in control animals, but was close to that in case of pulmonary thromboembolism after pretreatment with voltage-gated Na+ channel blockers lidocaine and ropivacaine. The increase of capillary filtration coefficient inversely correlated with values of capillary hydrostatic pressure. Thus, ranolazine and ivabradine exhibit the properties of voltage-gated Na+ channel blockers mainly in smooth muscles of pulmonary arterial vessels and promote the decrease in endothelial permeability.

Role of Na+,K+-ATPase in Bone Remodeling.

The effects of cardiotonic steroids (ouabain and digoxin) on the bone formation were studied using the organotypic tissue culture in combination with confocal microscopy. The expression of α1- and α3-isoforms of Na+,K+-ATPase was detected in cells of the bone tissue of 12-day-old chicken embryos. Ouabain in a concentrations 10-10 M (comparable with its endogenous concentration) can modulate transducer function of Na+,K+-ATPase and control the growth and proliferation bone tissue cells. Unlike ouabain, digoxin is not involved in the regulation of bone tissue growth in a 12-day-old chicken embryo.

[THE USING OF THE METHOD OF RECONSTRUCTION OF OPTICAL CROSS SECTIONS FOR INVESTIGATION OF THE TROPHOTROPIC EFFECTS OF ADRENALINE AND ATENOLOL].

The trophotropic effects of epinephrine and atenolol were investigated by using the organotypic culture method combined with the method of the reconstruction of optical cross sections. For the best possible image contrast was experimentally established the correction for Petri dish bottom thickness equal to 1 mm (objective lens Carl Zeiss). It was shown by method of the reconstruction of optical cross sections that growth zone in organotypic culture forms a multidimensional structure. In the presence of atenolol (10(-4) M) the thickness of the growth zone of the cardiac tissue explants was above the reference value 212%. The thickness of the growth zone in the presence of epinephrine (10(-9)-10(-13) M) did not differ from the control values. Experimentally was proved that atenolol mimics the trophotropic effects of epinephrine and these effects of epinephrine is realized primarily through ß1-adrenergic receptors.

Organotypic tissue culture investigation of homocysteine thiolactone cardiotoxic effect.

Homocysteine thiolactone was demonstrated to inhibit the growth of 10-12-day-old chicken embryo cardiac tissue explants at 7 × 10⁻9 -1 × 10⁻³ M concentrations in a dose-dependent manner. The maximal cardiotoxic effect of homocysteine thiolactone was detected at 1 × 10⁻³ M, which corresponds to severe hyperhomocysteinemia. The results of experiments on culturing of cardiac tissue explants in the medium containing homocysteine thiolactone (1 × 10⁻³ M) and ouabain at concentrations regulating the signal-transducing (1 × 10⁻¹° M) and pumping (1 × 10⁻8 M) functions of Na⁺,K⁺ -ATPase indicate that the cardiotoxic effect of homocysteine thiolactone is supposed to result from inhibition of the Na⁺,K⁺ -ATPase pumping function.