Preload-induced changes in isometric tension and [Ca2+](i) in rat myocardium

Abstract Preload-induced changes of active tension and [Ca2+]i are “dissociated” in mammalian myocardium. This study aimed to describe the distinct effects of preload at low and physiological [Ca2+]o. Rat RV papillary muscles were studied in isometric conditions at 25‡C and 0.33 Hz at 1 mM (hypo-Ca group) and 2.5 mM [Ca2+]o (normal-Ca group). [Ca2+]i was monitored with fura-2/AM. Increase of preload caused a rise of active tension in hypo-Ca and normal-Ca groups whereas peak fluorescence rose significantly only at low [Ca2+]o. End-diastolic tension, end-diastolic level of fluorescence, time-to-peak tension, but not time-to-peak of Ca2+ transient, progressively increased with preload. Mechanical relaxation decelerated with preload while Ca2+ transient decay time decreased in the initial phase and increased in the late phase, resulting in a prominent “bump” configuration. The “bump” was assessed as a ratio of its area to the fluorescence trace area. It was a new finding that the preload-induced rise of this ratio was twice as large in hypo-Ca. Our results indicate that preload-induced changes in active tension and [Ca2+]i are “dissociated” in rat myocardium, with relatively higher expression at low [Ca2+]o. Ca-dependence of Ca-TnC association/dissociation kinetics is thought to be a main contributor to these preload-induced effects.</jats:p

Clinical, Neurophysiological and Immunological Peculiarities of Myasthenia Gravis in Patients with Different Histologic Types of Thymoma

Thymoma is characterized by various clinical manifestations. About half of them are manifested as an asymptomatic course, others occur in a combination with different syndromes. 25% of patients develop compression of tumor blood vessels, nerves and organs of the mediastinum or clinical signs of germination of thymic tumor in other organs. 40% of patients are diagnosed with autoimmune diseases due to dysfunction of the thymus. Generalized myasthenia gravis (75%) is most frequently observed.The objective of the research was to study clinical and immunological peculiarities of myasthenia gravis depending on the size and histological type of thymoma.Materials and methods. The results of clinical and immunological, instrumental and histological examination of 30 patients with myasthenia on the background of thymoma were analyzed. The severity of the disease was assessed using clinical classification of the Myasthenia Gravis Foundation of America (MGFA, 2001).To determine the barrier function of phagocytic cells, phagocytosis activity of neutrophils was evaluated using the light microscope. The phagocytic index, the phagocytic number and the index of phagocytosis completion were determined. The suspension culture of Saccharomyces cerevisiae was used as a microbial agent. Preparations were stained using the Romanovsky-Himze methods. Neutrophilic leukocytes were separated from leukocyte suspension of peripheral blood. The expression of differentiation clusters CD3+, CD4+ and CD8+ on subpopulation of T- and B-cells were evaluated by indirect ELISA using monoclonal antibodies labeled with FITC-dye. To diagnose thymoma, we used spiral CT “Marconi” SeleCT/SP. For histologic study thymoma samples were fixed in 10% neutral formalin for 24 hours. The material was embedded in paraffin after posting through the chloroform in the usual way; then, sections with the thickness of 5-7 μm were prepared. Preparations were stained with hematoxylin and eosin.Results and conclusions. The severity of the clinical course of myasthenic syndrome on the background of thymoma does not depend on tumor size; it depends on the histologic type and immunological imbalance. The severest clinical picture was observed in patients with type AB thymoma and the least severe course of myasthenic symptoms was found in patients with lymphoid thymoma (type B1). Lymphoepithelial and epithelial thymomas were accompanied by similar immunological disorders. The reduction in the levels of CD3+ and CD4+ lymphocyte subpopulations can be used as a reliable diagnostic criterion. Lymphoid thymomas are characterized by a significant reduction in the indicators of the phagocytic index, the phagocytic number, and the level of CD8+ lymphocyte subpopulations as well as an increase in the level of CD4+ subpopulations. Surgical treatment as a method of choice in case of radical immunosuppression is indicated for all patients with confirmed thymoma regardless of its size and histological characteristics

Contractile Behavior of Right Atrial Myocardium of Healthy Rats and Rats with the Experimental Model of Pulmonary Hypertension

There is a lack of data about the contractile behavior of the right atrial myocardium in chronic pulmonary heart disease. We thoroughly characterized the contractility and Ca transient of isolated right atrial strips of healthy rats (CONT) and rats with the experimental model of monocrotaline-induced pulmonary hypertension (MCT) in steady state at different preloads (isometric force-length), during slow force response to stretch (SFR), and during post-rest potentiation after a period of absence of electrical stimulation (PRP). The preload-dependent changes in the isometric twitch and Ca transient did not differ between CONT and MCT rats while the kinetics of the twitch and Ca transient were noticeably slowed down in the MCT rats. The magnitude of SFR was significantly elevated in the MCT right atrial strips and this was accompanied by the significantly higher elevation of the Ca transient relative amplitude at the end of SFR. The slow changes in the contractility and Ca transient in the PRP protocol did not differ between CONT and MCT. In conclusion, the alterations in the contractility and Ca transient of the right atrial myocardium of monocrotaline-treated rats with pulmonary hypertension mostly concern the elevation in SFR. We hypothesize that this positive inotropic effect in the atrial myocardium may (partly) compensate the systolic deficiency of the right ventricular failing myocardium

From laser-induced line narrowing to electromagnetically induced transparency in a Doppler-broadened system

The laser-induced line narrowing effect in Doppler broadened systems was discovered thirty years ago. We have revisited this effect to determine its role for dense gases where recent experimental studies have found many intriguing atomic coherence effects. Using the density matrix approach, we study the width of electromagnetically induced transparency under different regimes of broadening

Slow force response and auto-regulation of contractility in heterogeneous myocardium

Classically, the slow force response (SFR) of myocardium refers to slowly developing changes in cardiac muscle contractility induced by external mechanical stimuli, e.g. sustained stretch. We present evidence for an intra-myocardial SFR (SFRIM), caused by the internal mechanical interactions of muscle segments in heterogeneous myocardium. Here we study isometric contractions of a pair of end-to-end connected functionally heterogeneous cardiac muscles (an in-series muscle duplex). Duplex elements can be either biological muscles (BM), virtual muscles (VM), or a hybrid combination of BM and VM. The VM implements an Ekaterinburg-Oxford mathematical model accounting for the ionic and myofilament mechanisms of excitation-contraction coupling in cardiomyocytes. SFRIM is expressed in gradual changes in the overall duplex force and in the individual contractility of each muscle, induced by cyclic auxotonic deformations of coupled muscles. The muscle that undergoes predominant cyclic shortening shows force enhancement upon return to its isometric state in isolation, whereas average cyclic lengthening may decrease the individual muscle contractility. The mechanical responses are accompanied with slow and opposite changes in the shape and duration of both the action potential and Ca2+ transient in the cardiomyocytes of interacting muscles. Using the mathematical model we found that the contractility changes in interacting muscles follow the alterations in the sarcoplasmic reticulum loading in cardiomyocytes which result from the length-dependent Ca2+ activation of myofilaments and intracellular mechano-electrical feedback. The SFRIM phenomena unravel an important mechanism of cardiac functional auto-regulation applicable to the heart in norm and pathology, especially to hearts with severe electrical and/or mechanical dyssynchrony. © 2012 Elsevier Ltd