Electrically based therapies for terminating atrial fibrillation (AF) currently fall into 2 categories: antitachycardia pacing and cardioversion. Antitachycardia pacing uses low-intensity pacing ...stimuli delivered via a single electrode and is effective for terminating slower tachycardias but is less effective for treating AF. In contrast, cardioversion uses a single high-voltage shock to terminate AF reliably, but the voltages required produce undesirable side effects, including tissue damage and pain. We propose a new method to terminate AF called far-field antifibrillation pacing, which delivers a short train of low-intensity electric pulses at the frequency of antitachycardia pacing but from field electrodes. Prior theoretical work has suggested that this approach can create a large number of activation sites ("virtual" electrodes) that emit propagating waves within the tissue without implanting physical electrodes and thereby may be more effective than point-source stimulation.
Using optical mapping in isolated perfused canine atrial preparations, we show that a series of pulses at low field strength (0.9 to 1.4 V/cm) is sufficient to entrain and subsequently extinguish AF with a success rate of 93% (69 of 74 trials in 8 preparations). We further demonstrate that the mechanism behind far-field antifibrillation pacing success is the generation of wave emission sites within the tissue by the applied electric field, which entrains the tissue as the field is pulsed.
AF in our model can be terminated by far-field antifibrillation pacing with only 13% of the energy required for cardioversion. Further studies are needed to determine whether this marked reduction in energy can increase the effectiveness and safety of terminating atrial tachyarrhythmias clinically.
Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves ...in a heterogeneous anatomical substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E) and a characteristic time, τ, for tissue depolarization that obeys the power law τ ∝ E(α). These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.
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Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known ...about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events.
We report on radio-controlled insect biobots by directing the flight of Manduca sexta through neuromuscular activation. Early metamorphosis insertion technology was used to implant metal wire probes ...into the insect brain and thorax tissue. Inserted probes were adopted by the developing tissue as a result of the metamorphic growth. A mechanically and electrically reliable interface with the insect tissue was realized with respect to the insect's behavioral and anatomical adoption. Helium balloons were used to increase the payload capacity and flight duration of the insect biobots enabling a large number of applications. A super-regenerative receiver with a weight of 650 mg and 750 muW of power consumption was built to control the insect flight path through remotely transmitted electrical stimulation pulses. Initiation and cessation of flight, as well as yaw actuation, were obtained on freely flying balloon-assisted moths through joystick manipulation on a conventional model airplane remote controller.
Ionic mechanism of electrical alternans Fox, Jeffrey J; McHarg, Jennifer L; Gilmour, Robert F., Jr
American journal of physiology. Heart and circulatory physiology,
02/2002, Volume:
282, Issue:
2
Journal Article
Peer reviewed
Open access
1 Department of Biomedical Sciences and 2 Department
of Physics, Cornell University, Ithaca, New York 14853-6401
Although alternans of
action potential duration (APD) is a robust feature of the ...rapidly
paced canine ventricle, currently available ionic models of cardiac
myocytes do not recreate this phenomenon. To address this problem, we
developed a new ionic model using formulations of currents based on
previous models and recent experimental data. Compared with existing
models, the inward rectifier K + current
( I K1 ) was decreased at depolarized potentials,
the maximum conductance and rectification of the rapid component of the
delayed rectifier K + current ( I Kr )
were increased, and I Kr activation kinetics were slowed. The slow component of the delayed rectifier K +
current ( I Ks ) was increased in magnitude and
activation shifted to less positive voltages, and the L-type
Ca 2+ current ( I Ca ) was modified to
produce a smaller, more rapidly inactivating current. Finally, a
simplified form of intracellular calcium dynamics was adopted. In this
model, APD alternans occurred at cycle lengths = 150-210 ms,
with a maximum alternans amplitude of 39 ms. APD alternans was
suppressed by decreasing I Ca magnitude or
calcium-induced inactivation and by increasing the magnitude of
I K1 , I Kr , or
I Ks . These results establish an ionic basis for APD alternans, which should facilitate the development of
pharmacological approaches to eliminating alternans.
action potential duration restitution; calcium current; potassium
currents
Low-energy anti-fibrillation pacing (LEAP) has been suggested as an alternative treatment in symptomatic fibrillation patients. It significantly lowers the energy required compared with standard ...1-shock defibrillation.
In this study, we investigated the mechanism of arrhythmia termination by LEAP and systematically analyzed the influence of shock period and timing on the success rate of LEAP.
We induced atrial and ventricular fibrillation in isolated canine hearts and applied LEAP and standard 1-shock defibrillation to terminate the arrhythmia. We simulated the arrhythmia and LEAP using a 2-dimensional bidomain human atrial model.
The ex vivo experiments showed successful termination of atrial fibrillation and ventricular fibrillation using LEAP, with an average 88% and 81% energy reduction, respectively, and both experiments and simulations verified that synchronization from virtual electrodes is the key mechanism for termination of arrhythmia by LEAP using modified Kuramoto phase plots and fraction of tissue excited (FTE) plots. We also observed in simulations that LEAP is more effective when the shock period is close to the dominant period and the first shock is delivered when FTE is decreasing.
Our results support synchronization as the mechanism for arrhythmia termination by LEAP, and its effectiveness can be improved by adjusting shock period and timing.
Despite recent advances in our understanding of the mechanism for ventricular fibrillation (VF), important electrophysiological aspects of the development of VF still are poorly defined. It has been ...suggested that the onset of VF involves the disintegration of a single spiral wave into many self-perpetuating waves. It has been further suggested that such a process requires that the slope of the electrical restitution relation be >or=to1. The same theory anticipates that a single spiral wave will be stable (not disintegrate) if the maximum slope of the restitution relation is <1. We have shown previously that the slope of the restitution relation during rapid pacing and during VF is >or=to 1 in canine ventricle. We now show that drugs that reduce the slope of the restitution relation (diacetyl monoxime and verapamil) prevent the induction of VF and convert existing VF into a periodic rhythm. In contrast, a drug that does not reduce the slope of the restitution relation (procainamide) does not prevent the induction of VF, nor does it regularize VF. These results indicate that the kinetics of electrical restitution is a key determinant of VF. Moreover, they suggest novel approaches to preventing the induction or maintenance of VF. (Circ Res. 1999;84:955-963.)
Insect-Machine Interface Based Neurocybernetics Bozkurt, Alper; Gilmour, Robert F.; Sinha, Ayesa ...
IEEE transactions on biomedical engineering,
2009-June, 2009-Jun, 2009-6-00, 20090601, Volume:
56, Issue:
6
Journal Article
Peer reviewed
We present details of a novel bioelectric interface formed by placing microfabricated probes into insect during metamorphic growth cycles. The inserted microprobes emerge with the insect where the ...development of tissue around the electronics during the pupal development allows mechanically stable and electrically reliable structures coupled to the insect. Remarkably, the insects do not react adversely or otherwise to the inserted electronics in the pupae stage, as is true when the electrodes are inserted in adult stages. We report on the electrical and mechanical characteristics of this novel bioelectronic interface, which we believe would be adopted by many investigators trying to investigate biological behavior in insects with negligible or minimal traumatic effect encountered when probes are inserted in adult stages. This novel insect-machine interface also allows for hybrid insect-machine platforms for further studies. As an application, we demonstrate our first results toward navigation of flight in moths. When instrumented with equipment to gather information for environmental sensing, such insects potentially can assist man to monitor the ecosystems that we share with them for sustainability. The simplicity of the optimized surgical procedure we invented allows for batch insertions to the insect for automatic and mass production of such hybrid insect-machine platforms. Therefore, our bioelectronic interface and hybrid insect-machine platform enables multidisciplinary scientific and engineering studies not only to investigate the details of insect behavioral physiology but also to control it.
Defining the cellular electrophysiological mechanisms for ventricular tachyarrhythmias is difficult, given the wide array of potential mechanisms, ranging from abnormal automaticity to various types ...of reentry and kk activity. The degree of difficulty is increased further by the fact that any particular mechanism may be influenced by the evolving ionic and anatomic environments associated with many forms of heart disease. Consequently, static measures of a single electrophysiological characteristic are unlikely to be useful in establishing mechanisms. Rather, the dynamics of the electrophysiological triggers and substrates that predispose to arrhythmia development need to be considered. Moreover, the dynamics need to be considered in the context of a system, one that displays certain predictable behaviors, but also one that may contain seemingly stochastic elements. It also is essential to recognize that even the predictable behaviors of this complex nonlinear system are subject to small changes in the state of the system at any given time. Here we briefly review some of the short-, medium-, and long-term alterations of the electrophysiological substrate that accompany myocardial disease and their potential impact on the initiation and maintenance of ventricular arrhythmias. We also provide examples of cases in which small changes in the electrophysiological substrate can result in rather large differences in arrhythmia outcome. These results suggest that an interrogation of cardiac electrical dynamics is required to provide a meaningful assessment of the immediate risk for arrhythmia development and for evaluating the effects of putative antiarrhythmic interventions.
Extravasation injury in a paediatric population Murphy, Adrian D.; Gilmour, Robert F.; Coombs, Chris J.
ANZ journal of surgery,
April 2019, 2019-04-00, 20190401, Volume:
89, Issue:
4
Journal Article
Peer reviewed
Open access
Background
Extravasation occurs when a drug is inadvertently administered outside of the vein. Depending on the substance involved, this may lead to tissue necrosis with significant long‐term ...morbidity. Children, particularly neonates, are particularly susceptible to extravasation with up to 70% of children in neonatal intensive care unit having some form of extravasation injury. These injuries are commonly referred to plastic surgeons for ongoing management.
Methods
We prospectively collected information on all extravasation injuries referred to the plastic surgery department in a children's hospital over an 18‐month period. Data collected included the agent involved in the extravasation, treatment and outcomes.
Results
In total, there were 43 extravasation injuries recorded on the hospital risk management system during the period of this study. All of these were referred to the plastic surgery team for ongoing management. Five patients (11%) underwent washout of their injuries. Three patients (7%) suffered injuries, which led to significant tissue necrosis, delayed healing and prolonged morbidity.
Conclusion
Smaller infants, particularly those being cared for in an intensive care setting, are at increased risk for extravasation injury. Early referral and treatment of high‐risk extravasation injuries may reduce the incidence of tissue loss and morbidity.
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