Pacemaker model

B. The pacemakers might last about ten years until the primary battery wears down (or until a rechargeable pacemaker has outlasted its patient), but in two to three years all pacemaker models always become obsolete with regard to new sales, and we need to make better, smaller, reliable, and more functional pacemakers to stay ahead of our competitors. 

McHale I would suggest that waves are more important in pacemaker cells than in smooth muscle cells. Our model for the way the urethra works is that the smooth muscle cells don t have waves but the pacemaker cells do. The oscillations of the pacemaker cells can then drive the smooth muscle cells. 

In spite of its usefulness, the pacemaker concept is oversimplified. It is often impossible to identify a specific pacemaker enzyme. When both catabolism and biosynthesis occur (e.g., as in the scheme in Fig. 11-2) it may be more useful to model the entire system with a computer than to try to identify pacemakers.7 8 It is also important to realize that reaction rates may be... 

Blockade of the 5-HT7 receptor has been shown to reduce epileptic activity in animal models. Audiogenic seizures induced in DBA/2J mice could be prevented by drugs in a rank order of potency corresponding to their affinity for the 5-HT7 receptor (95). The selective 5-HT7 receptor antagonist SB-258719 has been shown to reduce epileptic activity in an animal model for absence epilepsy, the WAG/Rij rat (65). It is believed to do so by modulating the pacemaker current Ih within the thalamus (96,97). The 5-HT7 receptor has been demonstrated to mediate depolarization within the anterodorsal thalamus by increasing lh through a cAMP-dependent, PKA-independent mechanism (96,97). 

The complete system responses are determined by the interactions, i.e. resonances, between the subthreshold and event-generating mechanisms. Again, in the HPA axis model, these interactions, so far, are rather simple and unidirectional. The circadian pacemaker modulates the H PA feedback loops in a nonlinear multiplicative way but is itself not influenced by the dynamics of the cortisol releasing processes. In contrast, in the neuronal and psychiatric models, the two subsystems are interlinked by a common control variable, the membrane voltage and the disease variable, respectively. These interlinks are a major source of very complex, inclusively chaotic dynamics [96, 111, 112]. 

Current models of pacemakers monitor the heart to determine the heart rate and do not interfere with the... 

Nonthermal effects may result from the possible interactions between RF fields and the various components of the biological material. Established effects include (1) The interference of radio frequencies with cardiac pacemakers is possible, however, new models of pacemakers are currently equipped with electronic filters making them immune to fields from... 

To demonstrate the ability of these hES cell-derived cardiomyocytes to survive, function and integrate in an in vivo heart. Professor Gepstein and colleagues assessed the ability to function as a biological pacemaker in an animal model of a slow heart rate and successfully paced its heart to normal rates. The animal model of... 

Heart Valves and Pacemakers. Pacemakers, which regulate the heart beat by electrical stimulation, have been used on humans since 1952, and implantable models have been used since 1958. The wires and electrodes are usually plastic coated for purposes of insulation, and the entire device is usually embedded in a plastic for protection from the body fluids. Over 60,000 of these pacemakers are placed in people each year. 

Fig. 5.46. Spatial patterns obtained in the three-variable model for cAMP signalling governed by eqns (5.12) supplemented with a term for the diffusion of extracellular cAMP. (a) Concentric (target) patterns, (b) Spiral patterns. The square area of 1 cm is represented by a mesh of 160 x 160 points in (a) and 100 X 100 points in (b). In (a) a pacemaker, represented by four points at the...

The waveform of the oscillations predicted by the model for cytosolic Ca (fig. 9.7) resembles that of the spikes observed for a number of cells stimulated by external signals. In particular, the rise in cytosolic Ca is preceded by a rapid acceleration that starts from the basal level although it originates from a different, nonelectrical mechanism, this pattern, which is reminiscent of the pacemaker potential that triggers autonomous spiking in nerve and cardiac cells (DiFrancesco, 1993), has been observed (Jacob et al, 1988) in epithelial cells stimulated by histamine (see fig. 9.3). As in the model by Meyer Stryer (1988), the oscillations of Ca " in the intracellular store have a saw-tooth appearance (see the dashed ctirve in fig. 9.7). Here, however, the phenomenon does... 

Block Wallace, 1982). An important study (Michel et al, 1993) recently showed that circadian rhythmicity occurs at the level of a single neuron in Bulla. This study indicated that the circadian variation of electrical activity involves the periodic variation of potassium conductance. Thanks to these advances, the Bulla circadian pacemaker has become a most promising experimental model for unravelling the molecular bases of circadian rhythmicity. Circadian pacemakers have also been identified in insects such as the cockroach (Page, 1982). 

Among circadian rhythms, one of the most studied by means of theoretical models is the sleep-wake cycle (Winfree, 1982 Daan, Beersma Borbely, 1984 Moore-Ede Czeisler, 1984 Strogatz, 1986,1987). A related topic of current interest in view of its therapeutical applications, which has also been approached theoretically (Kronauer, 1990 Kronauer Czeisler, 1993), pertains to the use of light to control the circadian pacemaker in humans. The property of temperature compensation, so characteristic of circadian rhythms, has also been the subject of theoretical investigations (Pavlidis Kauzmann, 1969 Lakin-Thomas, Brody Cote, 1991). 

Both, R., W. Finger R.A. Chaplain. 1976. Model predictions of the ionic mechanisms underlying the beating and bursting pacemaker characteristics of molluscan neurons. Biol. Cybern 23 1-11. 

Kawato, M. R. Suzuki. 1980. Two coupled neural oscillators as a model of the circadian pacemaker. J. Theor. Biol. 86 547-75. 

Kronauer, R.E. 1990. A quantitative model for the effects of light on the amplitude and phase of the deep circadian pacemaker, based on human data. In Sleep 90 (Proceedings of the Tenth European Congress on Sleep Research, Strasbourg), J. Home, ed. Pontenagel Press, Bochum, pp. 306-9. 

Wilders, R., H.J. Jongsma A.C.G. van Girmeken. 1991. Pacemaker activity of the rabbit sinoatrial node. A comparison of mathematical models. Biophys. J. 60 1202-16. 

Demir, S. S Clark, J. W., and Giles, W. R. (1999). Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart A unifying model Am. J. Physiol. 276, H2221-H2244. 

Besides protonation, electrophilic substitution at the 1- and 3-positions is another typical feature of azulene reactivity (55FCF(3)334, p. 367 59MI2, p. 310 61FOR(19)32 66MI1 84MI1 85HOU(5/2c)127, p. 249). Assisted by their polarity (see structures 232), azulenes have been even described as "pacemakers" (typical model compounds) of new electrophilic reactions (66CZ691) since they are colored, substitution can easily be observed and optimal conditions can be worked out. Examples mentioned earlier in the synthetic Section 2 are those of thiocyanation (Scheme 32) and alkylation (Scheme 38). In the case of occupied 1- and 3-positions reactions at C-5 and C-7 can be observed. 

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