This study describes the regulation of mechanical activity in the intact cardiac muscle, the effects of the free calcium transients and the mechanical constraints, and emphasizes the central role of the troponin complex in regulating muscle activity. A "loose coupling" between calcium binding to troponin and cross-bridge cycling is stipulated, allowing the existence of cross bridges in the strong conformation without having bound calcium on the neighboring troponin. The model includes two feedback mechanisms: 1) a positive feedback, or cooperativity, in which the cycling cross bridges affect the affinity of troponin for calcium, and 2) a negative mechanical feedback, where the filament-sliding velocity affects cross-bridge cycling. The model simulates the reported experimental force-length and force-velocity relationships at different levels of activation. The dependence of the shortening velocity on calcium concentration, sarcomere length, internal load, and rate of cross-bridge cycling is described analytically in agreement with reported data. Furthermore, the model provides an analytic solution for Hill's equation of the force-velocity relationship and for the phenomena of unloaded shortening velocity and force deficit. The model-calculated changes in free calcium in various mechanical conditions are in good agreement with the available experimental results.

This study examines the coupling of calcium binding to troponin with the force developed by the cross bridges in the skinned cardiac muscle. It emphasizes the key role of the troponin complex in regulating cross-bridge cycling and defines four distinct states of the troponin complex in the single-overlap region. These include a "loose-coupling" state, wherein cross bridges can exist in the strong conformation without having calcium bound to the neighbor troponin C. Published simultaneous measurements of the force and the bound calcium are used to calculate the apparent calcium binding coefficients. The force-length relationships at different free calcium concentrations are used to evaluate the cooperative mechanism. The dependence of the affinity of troponin for calcium on the number of force-generating cross bridges is the dominant cooperative mechanism. The proposed loose-coupling model, with a positive feedback of force on calcium binding, describes the role of calcium in force regulation and the force-length relationship in skinned cardiac muscle. The ability to simulate the rate of force development is demonstrated.

Exercise has a noted effect on skin blood flow and temperature. We aimed to characterize the normal skin temperature response to exercise by thermographic imaging. A study was conducted on ten healthy and active subjects (age=25.8+/-0.7 years) who were exposed to graded exercise for determination of maximal oxygen consumption (VO2 max), and subsequently to constant loads corresponding to 50%, 70%, and 90% of VO2 max. The skin temperature response during 20 min of constant load exercise is characterized by an initial descending limb, an ascending limb and a quasi-steady-state period. For 50% VO2 max, the temperature decrease rate was - 0.0075+/-0.001 degrees C/s during a time interval of 390+/-47 s and the temperature increase rate was 0.0055+/-0.0031 degrees C/s during a time interval of 484+/-99 s. The level of load did not influence the temperature decrease and increase rates. In contrast, during graded load exercise, a continuous temperature decrease of -0.0049+/-0.0032 degrees C/s was observed throughout the test. In summary, the thermographic skin response to exercise is characterized by a specific pattern which reflects the dynamic balance between hemodynamic and thermoregulatory processes.

The intracellular control mechanism leading to the well-known linear relationship between energy consumption by the sarcomere and the generated mechanical energy is analyzed here by coupling calcium kinetics with cross-bridge cycling. A key element in the control of the biochemical-to-mechanical energy conversion is the effect of filament sliding velocity on cross-bridge cycling. Our earlier studies have established the existence of a negative mechanical feedback mechanism whereby the rate of cross-bridge turnover from the strong, force-generating conformation to the weak, non-force-generating conformation is a linear function of the filament sliding velocity. This feedback allows the analytic derivation of the experimentally established Hill's equation for the force-velocity relationship. Moreover, it allows us to derive the transient length response to load clamps and the transient force response to sarcomere shortening at constant velocity. The results are in agreement with experimental studies. The mechanical feedback regulates the generated power, maintains the linear relationship between energy liberated by the actomyosin-ATPase and the generated mechanical energy, and determines the efficiency of biochemical-to-mechanical energy conversion. The mechanical feedback defines three elements of the mechanical energy: 1) external work done; 2) pseudopotential energy, required for cross-bridge recruitment; and 3) energy dissipation caused by the viscoelastic property of the cross bridge. The last two elements dissipate as heat.

The kinetics and the equilibrium adsorption of phosphate by collodion-coated alumina granules were investigated. Collodion-coated alumina can serve as a sorbent for phosphates in the treatment of hyperphosphatemic patients by haemoperfusion. The collodion coating lowers the surface area available for adsorption. The kinetics of adsorption were investigated by experiments in which the initial phosphate concentration, the quantity of sorbent and the grain size of sorbent were varied. The rate of adsorption is proportional to ta-1 where t is time and a is around 0.7.