Cristian Sevcencu

Autonomic alterations and cardiac changes in epilepsy

Studies with heart rate variability have revealed interictal autonomic alterations in patients with epilepsy. In addition, epilepsy is frequently associated with ictal tachycardia or bradycardia, which sometimes precedes the onset of seizures. Ictal tachycardia is sometimes associated with electrocardiography (ECG) morphologic changes and ictal bradycardia often progresses to asystole. Such cardiac manifestations of seizures have been hypothesized as possible causes for sudden unexplained death in epilepsy (SUPEP). The present review relates to interictal and ictal cardiac manifestations of epilepsy with focus on heart rate, heart rate variability, and ECG changes. Aspects of the supporting mechanisms are discussed and attention is drawn to the interaction between central and peripheral effects, interictal autonomic conditions, ictal autonomic discharges, and administration of antiepileptic drugs in shaping the ictal cardiac changes. Because these interactions are complex and not totally understood, closer surveillance of patients and more experimental work is necessary to elucidate the mechanistic support of autonomic and cardiac changes in epilepsy, and to design better strategies to avoid their undesirable effects. It is also suggested that some of these changes could be used as predictors or markers for the onset of seizures.

Propulsive activity induced by sequential electrical stimulation in the descending colon of the pig.

Abstract  This work was performed to study electrically induced contractions in the descending colon of pigs. Contractions were monitored using impedance planimetry and manometry. The luminal pressure, cross‐sectional area (CSA), latency and velocity of CSA decrease were compared when using 3 ms, 9, 12, 15 or 30 mA pulses at 10 Hz for 10 s, and 15 mA, 0.03, 0.3 or 3 ms pulses at 10 Hz for 10 s. Stimulation was performed prior and after the application of N(G)‐nitro‐l‐arginine methyl ester (l‐NAME) and atropine. In the untreated colon, contraction was always of an ‘off’ type. A current increase from 9 to 30 mA increased the pressure. An increase of pulse duration from 0.03 to 3 ms shortened the latency, accelerated contraction and increased pressure. By sequential stimulation, contractions were coordinated to propel semi‐fluid and solid luminal contents. l‐NAME increased the magnitude of CSA decrease. Atropine induced inhibitory effects on contractions elicited by 3 ms pulses and abolished contractions induced by 0.03 and 0.3 ms pulses. In conclusion: (i) electrical stimulation evokes‘off’ colon contractions, which can be coordinated to result in propulsion; (ii) the best combination for current and pulse duration to induce propulsive contractions is 15 mA and 3 ms; (iii) nitrergic and cholinergic pathways mediate responses to electrical stimulation.

Viscoelastic properties of isolated rat colon smooth muscle cells.

The measurement of the biomechanical properties of gastrointestinal smooth muscle cells is important for the basic understanding of digestive function and the interaction of muscle cells with the matrix. Externally applied forces will deform the cells depending upon their mechanical properties. Hence, the evoked response mediated through stretch‐sensitive ion‐channels in the smooth muscle cell membrane will depend upon membrane properties and the magnitude of the external force. The aim of this study was to test the hypothesis that gastrointestinal smooth muscle cells behave in a viscoelastic manner. Smooth muscle cells were dissociated from the muscle layers of the descending colon. The viscoelastic properties of the isolated cells were characterized by measuring the mechanical deflection response of the cell membrane to a negative pressure of 1 cm H2O applied across the cell through a micropipette and fitting the response to a theoretical viscoelastic solid model. The viscoelastic mechanical constants of the isolated cells (N = 9) were found to be as follows: k1 = 19.99 ± 2.86 Pa, k2 = 7.19 ± 1.21 Pa, μ = 25.36 ± 6.14 Pa s and τ = 4.84 ± 0.95 s. This study represents, to the best of our knowledge, the first quantitative mechanical properties of isolated living smooth muscle cells from the gastrointestinal tract. The mechanical properties determined in this study will be of use in future analytical and numerical smooth muscle cell models to better predict the mechanism between the magnitude of mechanical stimuli, mechanosensitivity and the evoked afferent responses.

Electrical stimulation – an evolving concept in the treatment of colonic motor dysfunctions

Abstract  Electrical stimulation of digestive organs is a new approach for the treatment of dismotility‐based diseases affecting the gastrointestinal (GI) tract. The most significant advancement in this field has been obtained with stomach stimulation. As a result, a fully implantable stimulation system to treat gastroparesis – the ‘Enterra’ system – is now commercially available. Similarly, electrical stimulation of the colon may become a valuable alternative to drug therapy and surgical procedures in the treatment of colonic motor dysfunctions. Over the past decade, several stimulation patterns to modulate colon motility have been tested in animal and human models. The results of these studies are reviewed here in connection with aspects regarding physiological mechanisms activated by electrical stimulation of the colon.

The effect of spinal cord stimulation on seizure susceptibility in rats.

Objectives:  Spinal cord stimulation (SCS) activates the thalamus, which may be involved in generation of seizures. SCS may therefore influence seizure susceptibility. We investigated the effect of SCS on seizure susceptibility when performed at low frequency (4 Hz) and a frequency in the typical range of SCS treatment (54 Hz).

Muscular vs. neural activation in propulsion induced by electrical stimulation in the descending colon of rats

The present experiments were performed on rat colon to study neurogenic and myogenic elicited propulsion induced by 0.3 and 30 msec long current pulses. The colon segments were stimulated sequentially and randomly. The obtained contractions displaced the intraluminal content in individual propulsion steps. The propulsion steps differed in displacement onset latency, distance, and velocity; the latency decreased while the distance and velocity increased from the proximal to the distal colon segments when performing sequential stimulation; the propulsion steps differed in latency when stimulation was performed randomly; the latency in the first propulsion step was three times longer when using 0.3 vs. 30 msec long pulses. When inhibiting cholinergic transmission by atropine, the propulsion induced by 0.3 msec pulses was blocked, while partially inhibited when using 30 msec pulses. Inhibiting nitric oxide synthesis by NG‐nitro‐L‐arginine methyl ester (L‐NAME) blocked propulsion induced by both of the pulse durations. In conclusion, electrical stimulation induces propulsion when using both 0.3 and 30 msec long pulses; stimulation using 0.3 msec pulses activates neurons, whereas 30 msec pulses depolarize muscles; in the absence of nitrergic transmission, propulsion cannot be induced by electrical stimulation.

Colon emptying induced by sequential electrical stimulation in rats

Electrical stimulation could be used to induce colon emptying. The present experiments were performed to establish a stimulation pattern to optimize the stimulation parameters and to test neural involvement in propulsion induced by electrical stimulation. Colon segments were sequentially stimulated using rectangular pulses. The resulting propulsive activity displaced intraluminal content in consecutive propulsion steps. The propulsion steps differed in displacement latency, distance, and velocity along the stimulated colon. Increasing the pulse duration or amplitude resulted in a decrease of the latency. Increasing the stimulation amplitude doubled the displacement distance. The frequencies tested in the present study did not affect propulsion. Inhibition of cholinergic and nitrergic pathways inhibited propulsion. Electrical stimulation can induce colonic propulsion. Motor differences are present along the descending colon. The most suitable combination of pulse parameters regarding colon stimulation is 0.3 ms, 5 mA, 10 Hz. Neural circuits are involved in propulsion when using these values.

Fascicle-Selectivity of an Intraneural Stimulation Electrode in the Rabbit Sciatic Nerve

The current literature contains extensive research on peripheral nerve interfaces, including both extraneural and intrafascicular electrodes. Interfascicular electrodes, which are in-between these two with respect to nerve fiber proximity have, however, received little interest. In this proof-of-concept study, an interfascicular electrode was designed to be implanted in the sciatic nerve and activate the tibial and peroneal nerves selectively of each other, and it was tested in acute experiments on nine anaesthetized rabbits. The electrode was inserted without difficulty between the fascicles using blunt glass tools, which could easily penetrate the epineurium but not the perineurium. Selective activation of all tibial and peroneal nerves in the nine animals was achieved with high selectivity (Ŝ = 0.98 ± 0.02). Interfascicular electrodes could provide an interesting addition to the bulk of peripheral nerve interfaces available for neural prosthetic devices. Since interfascicular electrodes can be inserted without fully freeing the nerve and have the advantage of not confining the nerve to a limited space, they could, e.g., be an alternative to extraneural electrodes in locations where such surgery is complicated due to blood vessels or fatty tissue. Further studies are, however, necessary to develop biocompatible electrodes and test their stability and safety in chronic experiments.

Gastrointestinal mechanisms activated by electrical stimulation to treat motility dysfunctions in the digestive tract: a review.

Studies performed to date have shown that electrical stimulation of the stomach and intestines can create or modulate motility functions in the gastrointestinal (GI) tract. Therefore, electrical stimulation of GI organs may become a valuable alternative to medication and surgical approaches in the treatment of GI motor dysfunctions. However, the mechanisms underlying the effects induced by electrical stimulation of the gut wall are not totally understood, and such knowledge is important for further development of stimulation methods and devices. Presently, it is known that electrical stimulation of GI organs triggers complex reactions comprising excitatory and inhibitory responses of the excitable components performing or controlling motility in the GI tract. I present here a review of what is known of the mechanisms of GI organ stimulation.

A review of electrical stimulation to treat motility dysfunctions in the digestive tract: effects and stimulation patterns

Electrical stimulation of the digestive organs may become a valuable alternative to pharmaceutical and surgical approaches to the treatment of gastrointestinal motor dysfunctions. For more than 40 years, encouraging results with electrical stimulation to activate motility in gastrointestinal organs have been published. The most significant achievements with this work have been either stimulation to attenuate the symptoms of gastroparesis or stimulation to modify the feeding behavior in obese patients. In addition, animal studies have investigated the different stimulation systems and methods to activate or inhibit transit in the small and large intestines. This article presents a review of the published literature on electrical stimulation of the stomach and intestines.