Differences in Mechanical, Electrical and Calcium Transient Performance of the Isolated Right Atrial and Ventricular Myocardium of Guinea Pigs at Different Preloads (Lengths).

There are only a few studies devoted to the comparative and simultaneous study of the mechanisms of the length-dependent regulation of atrial and ventricular contractility. Therefore, an isometric force-length protocol was applied to isolated guinea pig right atrial (RA) strips and ventricular (RV) trabeculae, with a simultaneous measurement of force (Frank-Starling mechanism) and Ca2+ transients (CaT) or transmembrane action potentials (AP). Over the entire length-range studied, the duration of isometric contraction, CaT and AP, were shorter in the RA myocardium than in the RV myocardium. The RA myocardium was stiffer than the RV myocardium. With the increasing length of the RA and RV myocardium, the amplitude and duration of isometric contraction and CaT increased, as well as the amplitude and area of the "CaT difference curves" (shown for the first time). However, the rates of the tension development and relaxation decreased. No contribution of AP duration to the heterometric regulation of isometric tension was found in either the RA or RV myocardium of the guinea pig. Changes in the degree of overlap of the contractile proteins of the guinea pig RA and RV myocardium mainly affect CaT kinetics but not AP duration.

In Vitro Anticancer Activity of the Light Stable Zinc Isotope (64Zn) Compounds.

BACKGROUND/AIM: Today, stable isotopes of zinc are actively used for diagnostic purposes in oncology. However, there is extremely limited data on the attempts to apply stable zinc isotopes in cancer therapy or about the molecular mechanisms of their effects on the biology of tumor cells. Therefore, in this in vitro research, we evaluated the cytotoxic activity of stable zinc isotope (64Zn) enriched compounds against malignant cells and determined the mechanisms of their action. MATERIALS AND METHODS: Malignant and non-malignant cells of different histogenesis were used as objects of the study. The effect of the Zn64aspartate, Zn64glutamate, and Zn64sulfate on cell viability in a comparative aspect was evaluated. Compounds containing 64Zn stable isotope enriched to 99.2%. Western blot analysis was used to determine the expression level of apoptosis regulatory proteins. RESULTS: Salts of 64Zn with amino acids had the most significant cytotoxic effect on malignant cells. The studied tumor cells, and especially MB16 melanoma cells were the most sensitive to the cytotoxic effects of Zn64aspartate. Zn64aspartate showed more significant cytotoxic activity than Zn aspartate (with natural isotope distribution) in the studied cell models. Zn64aspartate induced caspase-dependent cell death in A-549 cells and the p53-mediated apoptosis in melanoma cells. CONCLUSION: Malignant cells were more sensitive to the cytotoxic effect of the Zn64aspartate than normal cells. An increase in the intracellular concentration of 64Zn, and hence isotope mass balance changes, may lead to the suppression of the viability and proliferation of malignant cells. These results can become the basis for developing a new generation of anticancer drugs.

Inhibition of AT1 receptors by losartan affects myocardial slow force response in healthy but not in monocrotaline-treated young rats.

The slow force response (SFR) of a cardiac muscle to a sudden stretch is thought to be important in the regulatory adaptation of myocardial contraction. Autocrine-paracrine regulation pathways which involve angiotensin II are participating in this mechanism. On the other hand, renin-angiotensin-aldosterone system (RAS) is altered in hypertrophic or failing myocardium. We compared the effects of sudden stretch to SFR as well as to twitch and Ca2+ transient characteristics in rat myocardium with monocrotaline-induced heart failure with those in normal rat myocardium without and with inhibition of angiotensin II type-1 (AT1) receptors. Our findings indicate that the myocardium of rats with monocrotaline-induced right ventricular failure is deficient with activation of local RAS and therefore expresses blunted SFR, very similar to the depression of SFR observed in normal myocardium under inhibition of AT1 receptors. The "failing" myocardium does not further respond to the "putative" inhibition of AT1 receptors by losartan. In conclusion, SFR is related to autocrine-paracrine regulation of myocardial contraction in normal rat myocardium and that the involvement of RAS into stretch-induced modulation of contractility may be significantly altered in failing heart.