Recovery Of Electrical Activity Research Articles

A system for automated analysis of conductance correlations involved in recovery of electrical activity after neuromodulator deprivation in stomatogastric neuron models

Coregulation of ionic current levels, and specifically the changes that appear to take place in such relationships in response to deafferentation (i.e., neuromodulator deprivation), is thought to be one of the main explanations behind the phenomenon of recovery of electrical activity exhibited by stomatogastric (STG) neurons subjected to deafferentation [3]. Here, we are proposing an automated software system that allows for analysis of conductance correlations involved in recovery of electrical activity after deafferentation in STG neuron models. The system utilizes multi-objective evolutionary algorithms (MOEA) to explore the parameter space of conductance-based neuronal models in search of those models that exhibit activity resembling that of neurons in presence of neuromodulation, despite being simulated without it [1]. The system considers such models to represent “recovered” neurons, and compares the correlations discovered in a population of those models to relationships exhibited by “control” model neurons (i.e., those simulated with neuromodulators present). After the MOEA-based model construction is finished, the system automatically generates appropriate scatter plots, quantifies the relationships, finds differences between the two populations of models, and calculates the statistical significance of those differences. As a case study, we apply our system to the analyses of models of two very important STG neurons: the anterior burster (AB) and pyloric dilator (PD), proposed in [2]. In addition to demonstrating the applicability of this approach, we discuss interesting insights into the phenomenon of function recovery that all seem to involve the delayed rectifier (Kd) current.

Arousal-Related Reticular Neurons during Reduced Oxygen Tension: Resilience and Recovery of Electrical Activity

Whole-cell patch clamp recordings of the electrical activity of large medullary reticular formation neurons, in nucleus gigantocellularis, were performed under control conditions and under conditions of hypoxia or anoxia. Neurons were discovered whose activity was remarkably resilient during and after the reduction or loss of oxygen. Such cells may relate to the ability of the newborn brain to survive hypoxia/anoxia, and also may demonstrate the preservation of neurons involved in generalized CNS arousal, as would be appropriate for activating behavioral responses to the reduction or loss of oxygen.

Role of activation of cholinergic influences in recovery of electrical activity of the stomach and small intestine during the early postoperative period in rats

The effects of neostigmine and calcium pantothenate on electrical activity of the stomach and small intestine were studied in chronic experiments on rats after laparotomy with implantation of a probe into the jejunum and electrodes into different portions of the gastrointestinal tract. At the early terms after surgery, stimulation of endogenous acetylcholine release intensified electrical activity of the stomach, duodenum, and jejunum. Treatment with neostigmine and calcium pantothenate did not accelerate the recovery of the migrating myoelectrical complex, but promoted the recovery of the general intensity of action potential generation in the stomach and small intestine.

Role of Serotonin in the Recovery of Electrical Activity in the Stomach and Small Intestine of Rats during the Early Postsurgery Period

The effects of serotonin and 5-HT4 receptor agonist cisapride on electrical activity of the stomach and small intestine were studied in rats with postoperative ileus. Postoperative ileus was accompanied by the absence of the migrating myoelectric complex in the stomach and small intestine. All phases of the migrating myoelectric complex were successively recovered in the jejunum, duodenum, and stomach. Administration of serotonin and 5-HT4 receptor agonist cisapride into the jejunum was followed by the appearance of spike activity, which spread from the stomach to the jejunum. Intraintestinal treatment with cisapride and serotonin shortened the period to recovery of the migrating myoelectric complex to 3 and 4 days, respectively. Our results suggest that serotonin plays a role in the regulation of the migrating myoelectric complex at the early postoperation period.

Blockade of NMDA-receptors or calcium-channels attenuates the ischaemia-evoked efflux of glutamate and phosphoethanolamine and depression of neuronal activity in rat organotypic hippocampal slice cultures

We have investigated the effects of various insults on extracellular glutamate and phosphoethanolamine levels as well as electrical activity alterations in the early period following these insults in organotypic hippocampal slice cultures. Cultures prepared from 7-day-old rats were maintained in vitro for 7–14 days and then metabolic inhibition was induced: cultures were briefly exposed to potassium cyanide to induce chemical anoxia, 2-deoxyglucose with glucose removal to produce hypoglycaemia, or a combination of both to simulate ischaemia. Chemical anoxia induced a small increase in glutamate and a reversible decrease in evoked field potentials and these were greatly potentiated following simulated ischaemia: high, biphasic glutamate efflux and irreversible field potential abolition as well as increase in phosphoethanolamine levels were observed. We have characterised the effects of treatments using NMDA-receptor antagonists and the L-type calcium channel blocker diltiazem. Anoxia-induced glutamate accumulation was prevented by MK-801 and diltiazem D-AP5. Following simulated ischaemia, diltiazem totally prevented glutamate and phosphoethanolamine accumulations, whereas MK-801 did not block the first phase of glutamate accumulation and D-AP5 prevented none. We demonstrated that glutamate and phosphoethanolamine ischaemic-evoked efflux as well as the recovery of electrical activity in organotypic hippocampal slice cultures are sensitive to both NMDA-receptor and calcium-channel blockade. This model thus represents a useful in vitro system for the study of ischaemic neurodegeneration paralleling results reported using in vivo models.

The elusive extracellular AV nodal potential: studies from the canine heart, ex vivo.

Various forms of extracellular recordings from the AV node (AVN) have been reported. However, lack of consistent validation have precluded the use of such recordings in experimental and clinical studies. In 14 Langendorff perfused dog hearts, the triangle of Koch (TOK) was exposed and an octapolar electrode catheter (2 mm rings, 2 mm spacing) was inserted under the endocardium so that the bipolar pairs recorded electrograms from the apex to the base of the TOK. All recording were filtered between 0.05 and 250 Hz, except for a His bundle (Hb) recording (30-250 Hz) made from another bipolar electrode catheter placed in the aortic root. Transmembrane action potentials (AP) were recorded close to the sites of extracellular electrograms. Pin electrodes at the periphery of the bath were arranged to register two ECG leads from the volume conductor. During recovery of electrical activity 11 of 14 preparations developed a junctional rhythm that initially manifested only an AV nodal extracellular and corresponding intracellular AV nodal potentials followed gradually by conduction to the Hb and ventricles but no retrograde atrial activation; 3 preparations initially produced Hb rhythms based on extracellular and transmembrane AP recordings from the AVN and Hb. The amplitude and duration of the AVN extracellular potentials (average: 97 +/- 26 microV and 92 +/- 25 msec, respectively) during AVN rhythms, significantly differed from those during atrial pacing (262 +/- 185 microV and 78 +/- 26 msec, p < 0.05). Histologic sections of the sites underlying the electrodes recording AVN potentials showed AVN tissue throughout. We conclude that extracellular AV nodal potentials are independent waveforms with specific qualitative and quantitative characteristics that distinguish them from adjacent atrial, transitional, Hb or ventricular potentials.

Improvement of Spinal Cord Electrical Activity with Lazaroid (U74006F) During Operations on the Thoracic Aorta: Evaluation of a Novel Lipid Peroxidation Inhibitor

Reperfusion injury may contribute to spinal cord damage after cross-clamping of the thoracic aorta (AXC). Tirilazad (U74006F), a potent free radical scavenger and lipid peroxidation inhibitor, has proven to be beneficial in ischemia/reperfusion models. The authors investigated the efficacy of U74006F in preventing paraplegia following forty-five minutes of normothermic AXC distal to the origin of the left subclavian artery. Thirty-two mongrel dogs were assigned to receiving either vehicle as pretreatment (control, n = 7) or 1.5 mg/kg U74006F (group II, n=7) or 3 mg/kg U74006F (group III, n = 10) infused into the descending aorta distal to the clamp for twenty minutes during reperfusion, or 3 mg/kg U74006F IV as pretreatment twenty-five minutes before the onset of ischemia (group IV, n = 8). Mean proximal (BPpr) and distal (BPdx) aortic pressures and somatosensory evoked potentials (SEP) were measured at baseline and at minutes 2, 5, 7, 10, 15, 30, and 45 after AXC. SEP and neurologic outcome (Tarlov criteria) were assessed twenty-four hours postprocedure. There was no difference between BPpx or BP dx and their counterparts in the U74006F-treated animals and the control. SEP returned faster in all treatment groups when compared with controls. However, the neurologic outcome did not differ among groups. The authors conclude that although U74006F did not improve the neurologic outcome, it had a positive effect on the recovery of electrical activity of the spinal cord following transient ischemia. This suggests that the injury to the spinal cord induced by AXC is caused, in part, during reperfusion.

Dose-dependent cardiotoxic effect of amiodarone in cardioplegic solutions correlates with loss of dihydropyridine binding sites: in vitro evidence for a potentially lethal interaction with procaine.

Increasing evidence suggests that amiodarone treatment may represent a potential risk in patients exposed to cardiac surgery. Conversely, amiodarone has been suggested to be beneficial as an additive to cardioplegic solutions, but its use has not been tried in vivo. We evaluated hemodynamic, ECG, and possible toxicologic effects of amiodarone when added to the cardioplegic solution. Pigs weighing (70 +/- 2 kg, n = 24) were exposed to cardiopulmonary bypass (CPB) and hypothermic cardiac arrest for 1 h with Bretschneider's (BS) or St. Thomas' Hospital (St. Th.) cardioplegic solution. Amiodarone or the solvent was added to the solutions. Only pigs receiving the lowest dose of amiodarone (0.028 mg/g tissue) could be weaned from bypass. Higher doses resulted in graded myocardial contractures without recovery of electrical activity. Electron microscopy showed severely disintegrated myocytes and swollen mitochondria in amiodarone-exposed hearts. No changes in equilibrium binding characteristics were observed for beta-adrenoceptors, whereas maximum binding capacity (MBC) and receptor affinity for voltage-operated Ca2+ channels were dose-dependently decreased (mean 73%, p < 0.0005; 105%; p < 0.05). Ca2+ paradoxlike findings similar to those in pigs were inducible in isolated, in vitro perfused rat heart exposed to normothermic or hypothermic chemical arrest with BS and amiodarone. This model was therefore used to evaluate whether the observed myocardial damage was associated with excessive tissue Ca2+ accumulation. Addition of amiodarone to BS was associated with a significant increase in 45Ca2+ content in the heart, irrespective of temperature. Only 2 of 13 hearts recovered some degree of mechanical activity during reperfusion. When procaine (an antiarrhythmic drug with membrane-stabilizing properties, an effect that is potentiated by amiodarone) was removed from BS, 45Ca2+ accumulation did not differ from that in controls and mechanical activity recovered fully in 7 of 8 hearts. In conclusion, amiodarone added to Ca(2+)-free as well as Ca(2+)-containing cardioplegic solutions led to dose-dependent myocardial damage at reperfusion, irrespective of temperature. In parallel with clinical features was a reduction in maximum binding capacity and a decrease in affinity for the Ca2+ channel antagonist. Removal of procaine from BS prevented excessive Ca2+ accumulation and mechanical deterioration in isolated heart. We hypothesize that amiodarone administered under the conditions described may change the configuration of the Ca2+ channel, rendering it more permeable to Ca2+. Pharmacologic interaction between amiodarone and procaine apparently is at least partly responsible for the increased Ca2+ uptake and the stone-heart phenomenon during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Protective effect of phenytoin and its enhanced action by combined administration with mannitol and vitamin E in cerebral ischaemia.

To study the therapeutic effect of phenytoin on cerebral ischaemia and confirm whether or not the effectiveness of phenytoin could be enhanced by combined administration with free radical scavengers, twenty-five dogs were subjected to ischaemia, using the "canine model of the completely ischaemic brain regulated with a perfusion method". Five animals served as untreated controls, fifteen received treatment with several doses of phenytoin and five were treated with 10 mg/kg phenytoin, 2 g/kg mannitol and 30 mg/kg vitamin E. These drugs were administered prior to the production of ischaemia. After one hour ischaemia, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of the EEG, the higher the administered dosage, the better was the degree of recovery of the EEG. And the group which was treated with a combination of phenytoin, mannitol and vitamin E exhibited remarkable recovery of the EEG. With regard to the degree of brain swelling, a similar dose-related suppressive effect was seen in the phenytoin-treated groups. Furthermore, in the combination therapy group, brain swelling was attenuated significantly. Based on these results, it is concluded that phenytoin has a protective effect in cerebral ischaemia and it shows its most remarkable effect when given together with radical scavengers, such as mannitol and vitamin E.

Calcium Antagonists and Myocardial Protection: A Comparative Study of the Functional, Metabolie and Electrical Consequences of Verapamil and Nifedipine as Additives to the St. Thomas' Cardioplegic Solution*

Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, a comparative study has been undertaken in order to characterize the functional, metabolic and electrophysiological consequences resulting from the addition of dl-verapamil or nifedipine to the St. Thomas' Hospital cardioplegic solution. Hearts (n = 6 in each group) were subjected to cardioplegic infusion with the St. Thomas' solution with or without added verapamil (1.1 micromoles/liter) or nifedipine (0.075 micromoles/liter). After 35 minutes of normothermic (37 degrees C) ischemic arrest, reperfusion was initiated and functional recovery was measured and expressed as a percent of its pre-ischemic control value. Inclusion of nifedipine in the cardioplegic solution improved the post-ischemic recovery of cardiac output from its control value of 59.8 +/- 3.0% to 80.0 +/- 2.5%. The temporal characteristics for the post-ischemic recovery of electrical activity and contractile performance were uncomplicated and similar to control hearts. Inclusion of verapamil also improved the protective properties of the St. Thomas' solution with cardiac output recovering to 76.8% +/- 2.8%. However, in contrast to the control and nifedipine groups, the profile for functional recovery was complex. After an early initial recovery, pressure development declined for 0.5 to 6.0 minutes. This occurred despite the recovery of electrical activity. Hearts then exhibited a second phase of recovery where pressure development returned to normal and this was sustained for the duration of the experiment. Analysis of electrocardiographic characteristics revealed a significant prolongation of the P-P and P-Q interval during the first 10 minutes of reperfusion in the verapamil group.(ABSTRACT TRUNCATED AT 250 WORDS)

The protective effect of vitamin E on cerebral ischemia

Using the “canine model of the completely ischemic brain regulated with a perfusion method” the effects on cerebral ischemia of vitamin E, which is known to act as an antioxidant, were investigated. After pretreatment with vitamin E by oral or intravenous administration, cerebral blood flow was reduced to 1/10th the normal state and, 1 hour later, allowed to return to normal. Subsequent changes in electrical activity were observed, and the effects of vitamin E were evaluated. In the control group, no recovery of electrical activity was seen. In the groups given vitamin E, the recovery time was significantly shortened in the dogs given 30 mg/kg of vitamin E intravenously. Furthermore, in the groups treated with vitamin E, distinct recovery of electroencephalographic potentials at 3 hours after recirculation was apparent. These effects were more favorable in the case of intravenous administration than in the case of oral administration. These experimental results indicate that the administration of vitamin E is effective in protecting the brain from cerebral ischemia.

Experimental study of new cerebral protective substances - functional recovery of severe, incomplete ischaemic brain lesions pretreated with mannitol an fluorocarbon emulsion.

Using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the effects of mannitol (which acts as a free radical scavenger) and fluorocarbon emulsion (FC) (which has 0.1 micron of average particle size and a high oxygen-carrying capacity) on cerebral ischaemia were investigated. After pretreatment with the drugs, blood flow was reduced via the pump to 1/10 the normal state and 1 hour later, return to a normal state allowed. Subsequent changes in electrical activity were observed and the effectors of the drugs evaluated. In the control group, no recovery of electrical activity was seen, but in the animals treated with either mannitol or FC, incomplete, yet distinct recovery was apparent. In the animals administered mannitol together with FC, however, marked recovery was evident. These experimental results indicate that the combined administration of mannitol and FC is effective in protecting the brain from cerebral ischaemia.

Recovery of electrical activity of anterior abdominal wall muscles after prolonged atrophy

In experiments on anesthetised and awake cats the dynamics of the cerebral blood flow was studied by the thermoelectric method in one hemisphere in experimental lesion of the somatosensory zone of the opposite one. Temporary exclusion of the cortical area by cold produced evident hemodynamic changes, i. e. a two-phase vasoreaction and an initial blood flow decrease followed by a prolonged increase of blood supply, in the other hemisphere. Analogous vasoreactions were seen on unilateral extirpation of the cortical layer of the somatosensory zone, as well. Such vasoreactions indicate enhanced activity of the cortical structures in the intact hemisphere and may be considered as a compensatory reaction to the local lesion of certain cortical areas.

Potassium permeability activated by intracellular calcium ion concentration in the pancreatic beta-cell.

1. Membrane potentials and input resistance were measured in beta-cells from mouse pancreatic islets of Langerhans in a study designed to assess the role of a K permeability specifically blocked by quinine or quinidine and activated by intracellular calcium ion concentration ([Ca2+])i-activated PK). 2. Addition of 100 microM-quinine to the perifusion medium resulted in a 10--30 mV depolarization of the membrane and an increase in the input resistance of ca. 4.10(7) omega. 3. In the absence of glucose, 100 microM-quinine induced electrical activity. 4. In the presence of glucose, 100 microM-quinine abolished the burst pattern of electrical activity and very much reduced the graded response of spike frequency normally seen with different concentrations of glucose. 5. Addition of mitochondrial inhibitors, KCN, NaN3, DNP, CCCP, FCCP, to the perifusion medium containing glucose rapidly hyperpolarized the beta-cell membrane, inducing a concomitant decrease in input resistance. 6. In the presence of glucose, these mitochondrial inhibitors reversibly blocked electrical activity; upon removal of the inhibitor, recovery of electrical activity followed a biphasic pattern. 7. The effects of mitochondrial inhibitors were partially reversed by 100 microM-quinine. 8. It is proposed that the membrane potential of the beta-cell in the absence of glucose is predominantly controlled by the [Ca2+]i-activated PK. It is further suggested that this permeability to K controls the level for glucose stimulation and leads to the generation of the burst pattern.

INFLUENCE OF HORMONES ON RECOVERY OF ELECTRICAL ACTIVITY OF CRUSHED SCIATIC NERVES IN HYPOPHYSECTOMIZED RATS.

SummaryHypophysectomy delayed the recovery of electrical activity of crushed sciatic nerves in adult female rats. Administration of somatotrophic hormones, thyroxine, or testosterone propionate resulted in significant improvement in rate of recovery and accelerated it beyond that seen in the intact controls. When combination of hormones were given, a further acceleration of this effect was observed. The influence of cortisone acetate was equivocal.