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Biomedical subjects

Samuel Sideman

Publications and source records attributed to Samuel Sideman.

5 recordsLinked to original sources

Preface: the cellular communications maze.

Inter- and intracellular ionic and molecular communications are indispensable to the preservation of life and all organic functions. The cell constantly responds to a myriad of extracellular ionic and molecular signals, and cell behavior in single-cell or multicellular organisms is coordinated by these signals moving into, inside, or between the cells. The signals pass through the cell's phospholipidic plasma membrane by diffusion and, mostly, via protein transporters: gates, receptors, and/or ion pumps imbedded in the membrane. Each signaling pathway is a complex cause and effect chain of events involving intricate networks of interactions. For example, the extracellular signals, which are monitored by the cell's membrane cognate receptors, form ligand-receptor complexes. These are typically amplified by interaction with a coupling protein, mostly a G protein, and are diversified via intracellular signal transductions, either directly or via the activation of intracellular second messengers. The present volume focuses on signal-induced interactions that trigger specific responses of the effector system. Highlighting the cellular communication framework and the major parameters encountered in these complex interactive phenomena may help to familiarize the uninitiated with the complex phenomena involved in sustaining life.

Biological Transport↗

The adaptive intracellular control of cardiac muscle function.

This study explores the mechanisms dominating the regulation of the biochemical energy consumption and the mechanical output of the actin-myosin motor units, the crossbridges (Xbs), in the cardiac sarcomere. Our analytical model, which couples Xbs cycling dynamics with the kinetics of the free Ca(2+) binding to troponin-C (Tn-C), includes two feedback mechanisms: (1) a cooperativity mechanism, whereby the amount of force generating Xbs determines the affinity of calcium binding to the regulatory protein and the force-length relationship (FLR); and (2) a mechanical (negative) feedback, whereby the filament shortening velocity affects the rate of Xb turnover from the force- to the nonforce-generating state, allows the analytical solution for the muscle force-velocity relationship (FVR), and the linear relation between energy consumption and the generated mechanical energy. Our experimental and analytical studies of the force response to large-amplitude sarcomere length (SL) oscillations at various frequencies and constant [Ca(2+)] in the isolated tetanized rat trabeculae reveal that the generated force depends on the history of contraction and establishes the validity of these two feedbacks. The cooperativity mechanism generates counterclockwise (CCW) hystereses, where the muscle generates external work; while at higher frequencies the mechanical feedback produces clockwise (CW) hystereses, where the muscle behaves as a damper. The cooperativity provides the adaptive control of the cardiac response to short-term changes in the load by modulating Xb recruitment. The cardiac efficiency, defined as the ratio of the generated mechanical energy (i.e., external work and pseudo-potential energy) to the sarcomere energy consumption, is determined by the mechanical feedback, reflecting an inherent property of the single Xb. The efficiency is thus independent of the number of strong Xbs and is constant and load independent.

Adaptation, Physiological↗

Augmentation of dilated failing left ventricular stroke work by a physiological cardiac assist device.

A novel physiological cardiac assist device (PCAD), otherwise known as the LEVRAM assist device, which is synchronized with the heartbeat, was developed to assist the left ventricle (LV) in chronic heart failure (CHF). The PCAD utilizes a single cannula, which is inserted in less than 15 s through the apex of the beating LV by means of a specially designed device. Blood is withdrawn from the LV into the PCAD in diastole and is injected back to the LV, through the same cannula, during the systolic ejection phase, thereby augmenting stroke volume (SV) and stroke work (SW). CHF with dilated LV was induced in sheep by successive intracoronary injections of 100-microm beads. The sheep (92.2 +/- 25.9 kg, n = 5) developed stable CHF with increased LV end-diastolic diameter (69.4 +/- 3.3 mm) and end-diastolic volume (LVEDV = 239 +/- 32 mL), with severely reduced ejection fraction (23.8 +/- 7.6%), as well as mild-to-moderate mitral regurgitation. The sheep were anesthetized, and the heart was exposed by left thoracotomy. Pressure was measured in the LV and aorta (Millar). The SV was measured by flow meters and the LV volume by sonocrystals. Assist was provided every 10 regular beats, and the assisted beats were compared with the preceding unassisted beats, at the same LVEDV. The PCAD displaced 13.6 +/- 3.4 mL, less than 8% of LVEDV. Added SW was calculated from the assisted and control pressure-volume loops. The efficiency, defined as an increase in SW divided by the mechanical work of the PCAD, was 85.4 +/- 16.9%. We conclude that the PCAD, working with a small displaced blood volume in synchrony with the heartbeat, efficiently augments the SW of the dilated failing LV. The PCAD is suggested for use as a permanent implantable device in CHF.

Animals↗

Cardiac engineering--deciphering the cardiome.

Two monumental phenomena have shaped science and medicine in the last century and practically changed the world we live in. The first relates to the intimate interaction between engineering science and medicine-for example, technology and cardiology. The second relates to the globalization of science, the proliferation of the internet, and the unprecedented international interaction and scientific cooperation in facing difficult multidisciplinary challenges. The beneficial combination of these two megaphenomena, accompanied by significant environmental and sanitary changes, has greatly improved the quality of life and increased longevity around the globe. This conference, and the volume issuing from it, aims to explore the application of new developments in the microworld of cells and genes to gain better insight into the structure and function of the cardiac system, and hence to lead to better therapeutic modalities This multinational gathering of outstanding scientists from the various fields of the cardiac sciences is a living testimonial to human ingenuity and the spirit of international cooperation.

Cardiology↗

Molecular motion and cardiac muscle motor dynamics.

This paper reports on the kinetics of molecular motion in cardiac (and skeletal) muscles, studied by image analysis of the motility assay of an isolated actin filament sliding over isolated myosin heads that perform as linear motors. Image analysis allows us to study the dynamics of the crossbridges (Xbs) formed by the interactions between the actin molecule and the myosin heads, and to explore the rate kinetics of the interactions between the two. A most significant result pertains to the identification and characterization of two kinds of kinetics involved in Xb dynamics. The analysis of the acquired images suggests that Xb dynamics is determined by two distinctive kinetic mechanisms: fast physical kinetics that relates to the actin-myosin Xb attachment and detachment cycle and a process that is orders of magnitude slower in biochemical kinetics that relates to the reactions of nucleotide binding and dissociation.

Actins↗