Endogenous driving and synchronization in cardiac and uterine virtual tissues: bifurcations and local coupling

Cardiac and uterine muscle cells and tissue can be either autorhythmic or excitable. These behaviours exchange stability at bifurcations produced by changes in parameters, which if spatially localized can produce an ectopic pacemaking focus. The effects of these parameters on cell dynamics have been identified and quantified using continuation algorithms and by numerical solutions of virtual cells. The ability of a compact pacemaker to drive the surrounding excitable tissues depends on both the size of the pacemaker and the strength of electrotonic coupling between cells within, between, and outside the pacemaking region. We investigate an ectopic pacemaker surrounded by normal excitable tissue. Cell–cell coupling is simulated by the diffusion coefficient for voltage. For uniformly coupled tissues, the behaviour of the hybrid tissue can take one of the three forms: (i) the surrounding tissue electrotonically suppresses the pacemaker; (ii) depressed rate oscillatory activity in the pacemaker but no propagation; and (iii) pacemaker driving propagations into the excitable region. However, real tissues are heterogeneous with spatial changes in cell–cell coupling. In the gravid uterus during early pregnancy, cells are weakly coupled, with the cell–cell coupling increasing during late pregnancy, allowing synchronous contractions during labour. These effects are investigated for a caricature uterine tissue by allowing both excitability and diffusion coefficient to vary stochastically with space, and for cardiac tissues by spatial gradients in the diffusion coefficient

‘Twiddling’ of the pacemaker resulting in lead dislodgement

Twiddler’s syndrome is a rare condition in which patient manipulation of the pulse generator within its pocket may result in coiling of the lead and lead dislodgement, thereby causing pacemaker malfunction. Retraction of the electrode may cause phrenic nerve stimulation resulting in diaphragmatic stimulation and a sensation of abdominal pulsations. As the leads are further wrapped around the generator, rhythmic arm twitching may occur as a result of pacing of the brachial plexus.1 Twiddler’s syndrome was first described by Bayliss et al in 1968 as a complication of pacemaker implantation.2 It has also been reported with implantable cardioverter-defibrillators (ICDs)3 and cardiac resynchronisation therapy (CRT).4 This is a case report of an elderly lady with Twiddler’s syndrome resulting in pacemaker malfunction secondary to lead retraction, who emphatically denied any manipulation of her device. She subsequently underwent lead repositioning and appropriate counselling.peer-reviewe

Trends in Cardiac Pacemaker Batteries

Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future

Refurbishing Pacemakers: A Viable Approach

Cardiologists implant permanent pacemakers widely for indications like sick sinus syndrome and complete heart block. The guidelines for such implantations are well established1. However, in developing countries like India, all patients who need pacemakers do not receive them because of financial constraints. Even when such patients get a pacemaker, it is often a more affordable VVI pacemaker rather than the costly DDD pacemaker. The lack of a health insurance scheme and improper social support programs prevent the more widespread implantation of appropriate pacemakers. However, in the developed countries and in affluent pockets of developing countries like India, the pacemaker implantation rates are quite high. Often permanent pacemakers are implanted in the very old and people with predicted brief longevities, due to medico-legal and other social reasons. There are quite a few instances when pacemakers are explanted within a year or even within a few months. This is often due to the unfortunate death of the patient due to unrelated causes. Such pacemakers have battery lives, which are near normal. These can be explanted from the dead patient after taking consent from the relatives and “refurbished” for use in another needy patient. Refurbishing involves proper re-sterilization, checking of battery life, pacing mode and other parameters and re-labelling with the current parameters including predicted battery life. These refurbished pacemakers are a suitable alternative for the financially ‘no option’ group of patients who otherwise would not afford a pacemaker. These can last nearly as long as the original pacemakers. Even pulse generators whose shelf lives have expired can also be resterilised and used gainfully for the economically deprived

Stable Atrial Sensing on Long-Term Follow Up of VDD Pacemakers

Background: The hemodynamic advantages of maintaining AV synchrony through AV synchronous pacing are widely known as compared to single chamber pacing. DDD pacemaker implantation entails higher cost and is technically more challenging than the VDD pacemaker. Methods: Seventy one patients underwent VDD lead (Biotronik GmbH, St. Jude Medical and Medtronic Inc.) implantation at KEM hospital, Mumbai during a period of 3 years through subclavian, axillary and cephalic routes for degenerative, post-surgical or congenital high grade atrioventricular or complete heart block. They were followed up regularly for ventricular threshold and P wave amplitude of the floating atrial dipole. Results: Follow up data of almost 95% of patients is available for a period of 15.8 ± 6.7 months. P wave amplitude at implant was 2.1 ± 0.7mV and at follow up 1.1 ± 0.6mV with mean ventricular threshold of <0.5V at implant and <1V at follow-up. Conclusion: Implantation of a single lead VDD pacemaker is possible in all patients with symptomatic AV block and intact sinus node function without any technical complications. P wave sensing is reliable and consistent with floating atrial lead at an average follow up of 15.8 months, providing an excellent alternative to DDD pacemaker implantation

The neurochemical basis of photic entrainment of the circadian pacemaker

Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues

Modeling circadian and sleep-homeostatic effects on short-term interval timing

Short-term interval timing i.e., perception and action relating to durations in the seconds range, has been suggested to display time-of-day as well as wake dependent fluctuations due to circadian and sleep-homeostatic changes to the rate at which an underlying pacemaker emits pulses; pertinent human data being relatively sparse and lacking in consistency however, the phenomenon remains elusive and its mechanism poorly understood. To better characterize the putative circadian and sleep-homeostatic effects on interval timing and to assess the ability of a pacemaker-based mechanism to account for the data, we measured timing performance in eighteen young healthy male subjects across two epochs of sustained wakefulness of 38.67 h each, conducted prior to (under entrained conditions) and following (under free-running conditions) a 28 h sleep-wake schedule, using the methods of duration estimation and duration production on target intervals of 10 and 40 s. Our findings of opposing oscillatory time courses across both epochs of sustained wakefulness that combine with increasing and, respectively, decreasing, saturating exponential change for the tasks of estimation and production are consistent with the hypothesis that a pacemaker emitting pulses at a rate controlled by the circadian oscillator and increasing with time awake determines human short-term interval timing; the duration-specificity of this pattern is interpreted as reflecting challenges to maintaining stable attention to the task that progressively increase with stimulus magnitude and thereby moderate the effects of pacemaker-rate changes on overt behavior

Experimental analysis and computational modeling of interburst intervals in spontaneous activity of cortical neuronal culture

Rhythmic bursting is the most striking behavior of cultured cortical networks and may start in the second week after plating. In this study, we focus on the intervals between spontaneously occurring bursts, and compare experimentally recorded values with model simulations. In the models, we use standard neurons and synapses, with physiologically plausible parameters taken from literature. All networks had a random recurrent architecture with sparsely connected neurons. The number of neurons varied between 500 and 5,000. We find that network models with homogeneous synaptic strengths produce asynchronous spiking or stable regular bursts. The latter, however, are in a range not seen in recordings. By increasing the synaptic strength in a (randomly chosen) subset of neurons, our simulations show interburst intervals (IBIs) that agree better with in vitro experiments. In this regime, called weakly synchronized, the models produce irregular network bursts, which are initiated by neurons with relatively stronger synapses. In some noise-driven networks, a subthreshold, deterministic, input is applied to neurons with strong synapses, to mimic pacemaker network drive. We show that models with such “intrinsically active neurons” (pacemaker-driven models) tend to generate IBIs that are determined by the frequency of the fastest pacemaker and do not resemble experimental data. Alternatively, noise-driven models yield realistic IBIs. Generally, we found that large-scale noise-driven neuronal network models required synaptic strengths with a bimodal distribution to reproduce the experimentally observed IBI range. Our results imply that the results obtained from small network models cannot simply be extrapolated to models of more realistic size. Synaptic strengths in large-scale neuronal network simulations need readjustment to a bimodal distribution, whereas small networks do not require such change