Block Of Impulse Conduction Research Articles

Multifunctional biomimetic spinal cord: New approach to repair spinal cord injuries.

The incidence of spinal cord injury (SCI) has been gradually increasing, and the treatment has troubled the medical field all the time. Primary and secondary injuries ultimately lead to nerve impulse conduction block. Microglia and astrocytes excessively accumulate and proliferate to form the glial scar. At present, to reduce the effect of glial scar on nerve regeneration is a hot spot in the research on the treatment of SCI. According to the preliminary experiments, we would like to provide a new bionic spinal cord to reduce the negative effect of glial scar on nerve regeneration. In this hypothesis we designed a new scaffold that combine the common advantage of acellular scaffold of spinal cord and thermosensitive gel, which could continue to release exogenous basic fibroblast growth factor (BFGF) in the spinal lesion area on the basis of BFGF modified thermosensitive gel. Meanwhile, the porosity, pore size and material of the gray matter and white matter regions were distinguished by an isolation layer, so as to induce the directed differentiation of cells into the defect site and promote regeneration of spinal cord tissue.

Atrial Fibrillation and Fibrosis: Beyond the Cardiomyocyte Centric View

Atrial fibrillation (AF) associated with fibrosis is characterized by the appearance of interstitial myofibroblasts. These cells are responsible for the uncontrolled deposition of the extracellular matrix, which pathologically separate cardiomyocyte bundles. The enhanced fibrosis is thought to contribute to arrhythmias “indirectly” because a collagenous septum is a passive substrate for propagation, resulting in impulse conduction block and/or zigzag conduction. However, the emerging results demonstrate that myofibroblasts in vitro also promote arrhythmogenesis due to direct implications upon cardiomyocyte electrophysiology. This electrical interference may be considered beneficial as it resolves any conduction blocks; however, the passive properties of myofibroblasts might cause a delay in impulse propagation, thus promoting AF due to discontinuous slow conduction. Moreover, low-polarized myofibroblasts reduce, via cell-density dependence, the fast driving inward current for cardiac impulse conduction, therefore resulting in arrhythmogenic uniformly slow propagation. Critically, the subsequent reduction in cardiomyocytes resting membrane potential in vitro significantly increases the likelihood of ectopic activity. Myofibroblast densities and the degree of coupling at cellular border zones also impact upon this likelihood. By considering future in vivo studies, which identify myofibroblasts “per se” as a novel targets for cardiac arrhythmias, this review aims to describe the implications of noncardiomyocyte view in the context of AF.

Revisiting the reticulum: feedforward and feedback contributions to motor program parameters in the crab cardiac ganglion microcircuit.

The neurogenic heartbeat of crustaceans is controlled by the cardiac ganglion (CG), a central pattern generator (CPG) microcircuit composed of nine neurons. In most decapods, five "large" motor neurons (MNs) project from the CG to the myocardium, where their excitatory synaptic signals generate the rhythmic heartbeat. The processes of four "small" premotor neurons (PMNs) are confined to the CG, where they provide excitatory drive to the MNs via impulse-mediated chemical signals and electrotonic coupling. This study explored feedforward and feedback interactions between the PMNs and the MNs in the CG of the blue crab (Callinectes sapidus). Three methods were used to compare the activity of the MNs and the PMNs in the integrated CG to their autonomous firing patterns: 1) ligatures were tightened on the ganglion trunk that connects the PMNs and MNs; 2) TTX was applied focally to suppress selectively PMN or MN activity; and 3) sucrose pools were devised to block reversibly PMN or MN impulse conduction. With all treatments, the PMNs and MNs continued to produce autonomous rhythmic bursting following disengagement. Removal of PMN influence resulted in a significantly reduced MN duty cycle that was mainly attributable to a lower autonomous burst frequency. Conversely, after removal of MN feedback, the PMN duty cycle was increased, primarily due to a prolonged burst duration. Application of sucrose to block impulse conduction without eliminating PMN oscillations disclosed significant contributions of spike-mediated PMN-to-MN signals to the initiation and prolongation of the MN burst. Together, these observations support a view of the Callinectes CG composed of two classes of spontaneously bursting neurons with distinct endogenous rhythms. Compartmentalized feedforward and feedback signaling endow this microcircuit with syncytial properties such that the intrinsic attributes of the PMNs and MNs both contribute to shaping all parameters of the motor patterns transmitted to the myocardium.

Positively Active

The action of local anesthetics, containing a tertiary nitrogen, on mammalian nonmyelinated fibers of the rabbit's vagus nerve has been analyzed to determine whether the uncharged or the positively charged form of these compounds is responsible for their ability to block impulse conduction. The compounds studied were dibucaine, tetracaine, chlorpromazine, imipramine, and procaine. Impulse conduction was restored, in fibers in which it had been blocked by pretreatment with a local anesthetic, by increasing the pH of the perfusing solution from approximately 7.0 to 9.5; block was rapidly reestablished when the fibers were again perfused with the solution of pH approximately 7.0. From the way in which the size of the action potential varied with pH in nerve fibers pretreated with a local anesthetic. it has been concluded that the active form of the local anesthetic is the cation.

Cell swelling, impulse conduction, and cardiac arrhythmias in the failing heart. Opposite effects of angiotensin II and angiotensin (1–7) on cell volume regulation

The influence of hypotonic solution on cell volume and electrophysiology properties of the failing heart of cardiomyopathic hamsters (TO-2) was investigated. The results showed an increase in cell volume of quiescent isolated ventricular myocytes by 66% within 30 min. Angiotensin (1-7) [Ang (1-7)] (10(-8) M) administered to isotonic solution, elicited a gradual decline in cell volume and a significant decrease of the swelling-activated chloride current (I (Clswell)). The effect of Ang (1-7) on cell volume was inhibited by ouabain (10(-7) M). Angiotensin II (10(-8) M) caused cell swelling and increased I (Clswell). Experiments performed on isolated left ventricles of cardiomyopathic hamsters at an advanced stage of the disease, indicated that hypotonic solution prepared by diluting the normal Krebs solution by 25%, showed a gradual decrease of conduction velocity, generation of early after depolarizations and block of impulse conduction within 10 min. Implications to myocardial ischemia are discussed.

Lidocaine prevents referred hyperalgesia associated with cystitis

Lidocaine produces analgesia by inhibiting excitation of nerve endings or blocking impulse conduction in peripheral nerves. This study was performed to determine whether intrathecal or intravesical administration of lidocaine prior, or subsequent, to induction of chemical cystitis in rats would block referred mechanical hyperalgesia. Intrathecal or intravesical lidocaine was administered 15 (intrathecal) or 30 (intravesical) min before intravesical instillation of saline or 1 mM acrolein (400 microl) or 4 hr after saline or acrolein instillation in female Wistar rats. Mechanical sensitivity of hind paws was determined at 24 hr prior to any treatment (baseline) and, 4, 24, and 48 hr after intravesical instillation of acrolein or saline. Also, nerve growth factor (NGF) content was measured in bladder and dorsal root ganglia (DRG). Pre-treatment with intrathecal or intravesical lidocaine attenuated acrolein-induced referred mechanical hyperalgesia of the hind paws. Lidocaine administered after acrolein instillation did not alter referred hyperalgesia. Lidocaine treatment prior to or after induction of cystitis reduced NGF content in the bladder. These results indicate that pre-treatment with lidocaine attenuates referred hyperalgesia associated with cystitis. Lidocaine treatment 4 hr after induction of cystitis failed to prevent referred hyperalgesia despite a similar decrease in bladder NGF. Neurourol. Urodynam. (c) 2009 Wiley-Liss, Inc.

Effects of potassium ions on dentine sensitivity in man

Objective To determine the effect of applying 500 mmol/l KCl at a pressure of 150 mm Hg above atmospheric to exposed dentine on pain sensation evoked by probing and air blast stimuli in human subjects. Design The experiments were carried out on 14 pairs of premolars in 14 human subjects (aged 17–30 years). Dentine was exposed at the tip of the buccal cusp, etched with acid and covered with saline, then 500 mmol/l KCl in Ringer's was applied at a pressure of 150 mm Hg for 4 min. Mechanical probing and air-drying stimuli were performed before and 2, 10, 20, 30 min after applying the KCl solution. The subject indicated the intensity of any pain produced on a visual analogue scale (VAS). Pulpal blood flow was recorded with a laser Doppler flow meter. Exactly the same procedure was carried out on the contralateral tooth except that 500 mmol/l NaCl in Ringer's was used in place of the KCl solution. Results The pain responses to mechanical probing and air blast stimuli were significantly reduced during the first 10 min after applying the KCl but not the NaCl solution. Pulpal blood flow did not change significantly after either treatment. Conclusion Potassium ions, when applied to exposed dentine at a pressure of 150 mm Hg above atmospheric, produced temporary block of impulse conduction in sensory nerve endings in the dentine or pulp.

Mechanisms of the Preventive Effect of Pilsicainide on Atrial Fibrillation Originating From the Pulmonary Vein

It has been shown that pilsicainide terminates atrial fibrillation (AF) by pharmacologic pulmonary vein (PV) isolation. However, whether it can prevent AF induction originating from the PV by the same mechanism is still uncertain. Rapid pacing from the left superior PV (LSPV) and the right atrial free wall (RAF) was performed to induce AF during electrical stimulation of both cervical vagal nerves in 6 anesthetized dogs and during the infusion of acetylcholine (ACh) in 8 isolated atria. Rapid pacing induced AF in all dogs, regardless of the pacing site, before pilsicainide. Pilsicainide (1 mg/kg) prevented AF during rapid pacing from the LSPV, with an impulse conduction block between the LSPV and the left atrial free wall (LAF). However, the same dose of pilsicainide did not prevent AF when pacing was performed from the RAF. Pilsicainide partially restored the action potential duration shortened by ACh infusion and prevented AF with an impulse conduction block at the LSPV-left atrial junction in all isolated preparations tested. The results suggest that (1) impulse conduction block at the LSPV-LA junction is the underlying mechanism of pilsicainide-induced prevention of vagally-induced AF originating from the LSPV and (2) pilsicainide is more effective at preventing AF originating from the LSPV than that from the RA.

Nerve control of type 2A MHC isoform expression in regenerating slow skeletal muscle.

Bupivacaine-induced regeneration was studied in rat soleus muscle under several conditions, with the focus on type 2A and type 1 myosin heavy chain (MHC) isoform expression. In denervated muscles, type 1 was absent, whereas type 2A was widely expressed, a pattern of regeneration which appeared to be independent of fibrillation activity of the muscle. Both type 1 and type 2A isoforms were absent in muscles regenerated during tetrodotoxin (TTX) block of impulse conduction in the sciatic nerve, but type 2A was still present when the TTX block was associated with the vinblastine block of axoplasmic flow; vinblastine block alone caused the coexpression of type 1 and type 2A isoforms in the majority of fibers. These results suggest that axoplasmic flow carries some chemical factor that inhibits 2A MHC isoform expression. The results are also of clinical interest, contributing to the understanding of factors controlling muscle differentiation and adaptation.

Pediatric Regional Anesthesia: Beyond the Caudal

Pediatric Regional Anesthesia: Beyond the Caudal

Induction of Atrioventricular Node Reentrant Tachycardia With Adenosine: Differential Effect of Adenosine on Fast and Slow Atrioventricular Node Pathways

Objectives. This study sought to evaluate the sensitivity of fast and slow atrioventricular (AV) node pathways to incremental doses of adenosine in patients with typical AV node reentrant tachycardia.Background. Although adenosine is known to depress conduction through the AV node, the relative sensitivity to adenosine of the anterograde fast and slow pathways in patients with dual AV node pathways and typical AV node reentrant tachycardia has not previously been studied.Methods. Sixteen patients with dual AV node physiology and typical AV node reentrant tachycardia and 10 control patients were given incremental doses of adenosine during atrial pacing.Results. In 14 of 16 patients with dual-AV node physiology, administration of small doses of adenosine during atrial pacing led consistently to transient block of impulse conduction in the fast pathway before block in the slow pathway, resulting in abrupt prolongation of the AH interval with continued 1:1 AV conduction. The mean (±SD) doses of adenosine required to cause conduction block in the fast and slow pathways were 2.7 ± 3.0 and 7.2 ± 4.7 mg, respectively (p = 0.004). In 9 of 16 patients, administration of low dose adenosine led to initiation of AV node reentrant tachycardia. The control patients showed no abrupt increases in AH interval with administration of adenosine during atrial pacing.Conclusions. In most patients with dual AV node pathways and typical AV node reentrant tachycardia, the fast pathway is more sensitive than the slow pathway to the effects of adenosine.

Cutaneous field stimulation (CFS): a new powerful method to combat itch

Scratching the skin, while instantly relieving itch, often aggravates itch over time due to skin injury. To relieve itch, without damaging the skin, a new technique termed cutaneous field stimulation (CFS) was developed and tested on 21 subjects. CFS uses a flexible plate with needle-like electrodes ( n=16) to electrically stimulate nerve fibres in the superficial skin. The electrodes were stimulated consecutively (4 Hz per electrode, pulse duration 1 ms, intensity 0.4–0.8 mA, 25 min). CFS resulted in a pricking and burning sensation that usually faded rather quickly. The burning sensation was still present during a selective block of impulse conduction in myelinated fibres indicating that nociceptive C-fibres are activated by CFS. Furthermore, a flare reaction developed around the CFS electrodes indicating activation of axon reflexes in nociceptive C-fibres. Itch, elicited by transdermal iontophoresis of histamine, was abolished within the skin area pre-treated with CFS, and was reduced to 14% of control 10 cm distally. Contralateral effects were small or non-existent. After 4 h, itch was reduced ipsilaterally to 32% of control. In comparison, 2 h after transcutaneous electrical nerve stimulation (TENS; 10–20 mA, 100 Hz, 25 min) ipsilateral itch was reduced to 56% of control. In conclusion, CFS offers a powerful new method for combating itch. It is suggested that CFS acts through endogenous central inhibitory mechanisms that are normally activated by scratching the skin.

Central release of tracer after noxious stimulation of the skin suggests non-synaptic signaling by unmyelinated fibers.

Injury to a peripheral nerve causes central changes of various nature and complexity reflecting activation of multiple signaling mechanisms. In a previous study we reported that nerve lesion triggers central release of a tracer, wheatgerm-agglutinin conjugated to horse-radish peroxidase, by unmyelinated fibers in the spinal cord. The released tracer occupies the space between nerve terminals and dendrites without extending into the synaptic cleft. We interpreted this to suggest release of unidentified endogenous factor(s) at nonsynaptic sites, which may contribute to the signaling of peripheral injury to the central nervous system. For such signaling to occur, a message must first be communicated along the axon. This message may depend on axonal transport and/or altered electrical activity. In pilot experiments we observed that application of tetrodotoxin (to block impulse conduction) to the intact nerve did not result in tracer release. We hypothesized that the message might be the sustained discharge of C fibers that occurs after injury. We show here that selective activation of C fibers (by applying mustard oil to the hindlimb of anesthetized rats) causes central release of tracer previously transported from the sciatic nerve to superficial laminae of the dorsal horn.

Potentiation by capsaicin of lidocaine's tonic impulse block in isolated rat sciatic nerve.

Compound action potentials (CAPs) of A- and C-fibers were recorded from isolated sciatic nerves of the rat to determine whether tonic block of impulse conduction induced by lidocaine was affected by low doses of capsaicin. Capsaicin alone (50 microM) did not change the CAPs of either A- or C-fibers. Although the lower concentrations of capsaicin (5-30 microM) caused no change of the tonic blocking action of lidocaine, 30 min of 50 microM capsaicin administration did induce a significant potentiation of tonic block. Capsaicin's potentiating effects were partially reversed after 30 min of wash. These results suggest that capsaicin may be a useful agent for the potentiation of impulse blockade by lidocaine.

The Effect of Tetraethylammonium Chloride on the Impulse Conduction Block by bupivacaine

The Effect of Tetraethylammonium Chloride on the Impulse Conduction Block by bupivacaine

Primary afferent depolarization of muscle afferents elicited by stimulation of joint afferents in cats with intact neuraxis and during reversible spinalization.

1. In the anesthetized and artificially ventilated cat, stimulation of the posterior articular nerve (PAN) with low strengths (1.2-1.4 x T) produced a small negative response (N1) in the cord dorsum of the lumbosacral spinal cord with a mean onset latency of 5.2 ms. Stronger stimuli (> 1.4 x T) produced two additional components (N2 and N3) with longer latencies (mean latencies 7.5 and 15.7 ms, respectively), usually followed by a slow positivity lasting 100-150 ms. With stimulus strengths above 10 x T there was in some experiments a delayed response (N4; mean latency 32 ms). 2. Activation of posterior knee joint nerve with single pulses and intensities producing N1 responses only, usually produced no dorsal root potentials (DRPs), or these were rather small. Stimulation with strengths producing N2 and N3 responses produced distinct DRPs. Trains of pulses were clearly more effective than single pulses in producing DRPs, even in the low-intensity range. 3. Cooling the thoracic spinal cord to block impulse conduction, increased the DRPs and the N3 responses produced by PAN stimulation without significantly affecting the N2 responses. Reversible spinalization also increased the DRPs produced by stimulation of cutaneous nerves. In contrast, the DRPs produced by stimulation of group I afferents from flexors were reduced. 4. Conditioning electrical stimulation of intermediate and high-threshold myelinated fibers in the PAN depressed the DRPs produced by stimulation of group I muscle and of cutaneous nerves. 5. Analysis of the intraspinal threshold changes of single Ia and Ib fibers has provided evidence that stimulation of intermediate and high threshold myelinated fibers in the posterior knee joint nerve inhibits the primary afferent depolarization (PAD) of Ia fibers, and may either produce PAD or inhibit the PAD in Ib fibers, in the same manner as stimulation of cutaneous nerves. In 7/16 group I fibers the inhibition of the PAD was increased during reversible spinalization. 6. The results obtained suggest that intermediate and high-threshold myelinated fibers in the PAN have the same actions on Ia and Ib fibers as intermediate and high-threshold cutaneous afferents and may therefore be considered as belonging to the same functional system. They further indicate that in anesthetized preparations the pathways mediating the PAD of group I fibers, as well as the pathways mediating the inhibition of the PAD, may be subjected to a descending control that is removed by spinalization.

Differential actions of brevetoxin on phrenic nerve and diaphragm muscle in the rat

The mechanism of inhibition of skeletal muscle function by brevetoxin (PbTX-3) was examined in vitro in the rat phrenic nerve-diaphragm preparation. PbTX-3 in low concentrations (< 0.06 μM) preferentially blocked conduction in the phrenic nerve without altering the resting membrane potential of the muscle fibers. Endplate potential failure occurred in an all-or-none fashion in the presence of PbTX-3 (> 0.06 μM). An increase in the frequency of miniature endplate potentials resulting from nerve terminal depolarization was observed only after endplate potential failure. Higher concentrations of toxin (> 0.3 μM) depressed directly-elicited muscle twitches and produced significant muscle membrane depolarization. Tetrodotoxin was effective in reversing membrane depolarization and alterations in MEPP frequency caused by PbTX-3. These findings suggest that diaphragmatic failure in PbTX-3 is primarily caused by a block of impulse conduction in the phrenic nerve due to a higher sensitivity of nerve than muscle membrane to the toxin.

Subblocking concentrations of local anesthetics: effects on impulse generation and conduction in single myelinated sciatic nerve axons in frog.

Phenomena seen in axons exposed to subblocking doses serve as the basis for interpreting clinical and behavioral observations during onset and recovery of peripheral nerve block. To delineate the changes in excitability and in impulse conduction caused by subblocking concentrations of local anesthetics (LAs) in myelinated peripheral nerve fibers, LAs were applied to excised frog sciatic nerves while impulse conduction was monitored in single axons. For concentrations ranging from 0.01 to 1.2 times the LA concentration needed to block impulse conduction, three measures of susceptibility to LA were made to quantify the action of the drugs on "resting" fibers (firing rates < or = 0.5 Hz): the increase in the threshold for electrical activation of impulses, the increase in conduction latency reflecting the slowing of impulse conduction in the region exposed to LA, and the "critical blocking concentration" of LA just sufficient to prevent impulse conduction in the recorded fiber. Wide interfiber variation in these variables was observed (e.g., for lidocaine, latency increases at block ranged from 66% to 257% of control, blocking concentrations ranged from 0.29 to 1.40 mM), which was not correlated with fiber diameter (as indicated by resting conduction velocity). Mathematical modeling of impulse conduction in fibers exposed to LA demonstrated that the interfiber variation in susceptibility to LA block could result from interfiber differences in the density of sodium and potassium channels. The effects of LA were also studied in active fibers (firing rates > 0.5 Hz). Local anesthetics reversibly inhibited two normally occurring afteroscillations in membrane threshold related to afterpotentials following an impulse. These were "superexcitability," a transient lowering of threshold lasting as long as 1 s, and "depression," a phase of raised threshold peaking within 2-4 s after an impulse and recovering slowly over several minutes. Impulse activity also transiently increased the apparent potency of LAs. Such "use-dependent" increases in threshold and decreases in conduction velocity showed kinetics that were agent specific, lasting 1 s after a burst of impulses for lidocaine and lasting > 10 s for bupivacaine. At low concentrations, within the range of nontoxic plasma concentrations after systemic administration, the predominant actions of LAs on conducting fibers were transient decreases in excitability and conduction velocity in combination with a reduction of intrinsic oscillatory aftereffects of impulse discharge. These effects may degrade decoding of information in discharge patterns without actually blocking conduction of infrequent impulses, suggesting how functional blockade of coordinated movement and perception may occur even without complete blockade of impulse conduction.

Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans.

1. Capsaicin, the algesic substance in chilli peppers, was injected intradermally in healthy human subjects. A dose of 100 micrograms given in a volume of 10 microliters caused intense pain lasting for a few minutes after injection and resulted in a narrow area of hyperalgesia to heat and a wide surrounding area of hyperalgesia to mechanical stimuli (stroking) lasting for 1-2 h. 2. Nerve compression experiments with selective block of impulse conduction in myelinated (A) but not in unmyelinated (C) fibres indicated that afferent signals in C fibres contributed to pain from capsaicin injection and to heat hyperalgesia, whereas conduction in afferent A fibres was necessary for the perception of mechanical hyperalgesia. 3. Electrical intraneural microstimulation normally eliciting non-painful tactile sensations was accompanied by pain when the sensation was projected to skin areas within the region of mechanical hyperalgesia induced by capsaicin injection. 4. The threshold for pain evoked by intraneural microstimulation was reversibly lowered and pain from suprathreshold stimulation was exaggerated during the period of mechanical hyperalgesia, regardless of lidocaine anaesthesia of the cutaneous innervation territory of the stimulated fibres. 5. The results indicate that hyperalgesia to stroking on a skin area surrounding a painful intradermal injection of capsaicin is due to reversible changes in the central processing of mechanoreceptive input from myelinated fibres which normally evoke non-painful tactile sensations.

Prevention of myocardial intracellular edema induced by St. Thomas' Hospital cardioplegic solution

During cardiac surgery, the heart is infused with cold crystalloid cardioplegic solutions such as St. Thomas' Hospital (StT) solution [ 1], which contains high concentrations of K + and Mg 2+. The high K + and Mg 2+ block impulse conduction and inhibit Ca 2+ influx, thereby arresting the heart and reducing cardiac oxygen consumption. Nevertheless, myocardial edema and post-operative abnormalities have been noted after cardioplegia and attributed to ischemia and reflow or to hypothermia. We found, however, that cold StT (9°C) was hypotonic and induced cell swelling in the absence of ischemic injury. Cell swelling in cold StT was not due to hypothermia alone, but rather was caused by KCl influx and was prevented by partially replacing Cl − with an impermeant anion. After exposure to cold StT, cells transiently shrank to less than control volume on rewarming in physiological saline (Tyrode's solution, 37°C). The transient shrinkage was blocked by ouabain suggesting that Na + loading of depolarized hypothermic cells and Na +K + pump activation on rewarming were responsible. Hypothermic ventricular cells seem to follow Donnan equilibrium, and the product of [K +] × [Cl −] in cardioplegic solutions affects cell volume in the absence of ischemic injury.