Analgesic dorsal root ganglion field stimulation blocks both afferent and efferent spontaneous activity in sensory neurons of rats with monosodium iodoacetate-induced osteoarthritis.

OBJECTIVES: Chronic joint pain is common in patients with osteoarthritis (OA). Non-steroidal anti-inflammatory drugs and opioids are used to relieve OA pain, but they are often inadequately effective. Dorsal root ganglion field stimulation (GFS) is a clinically used neuromodulation approach, although it is not commonly employed for patients with OA pain. GFS showed analgesic effectiveness in our previous study using the monosodium iodoacetate (MIA) - induced OA rat pain model. This study was to evaluate the mechanism of GFS analgesia in this model. METHODS: After osteoarthritis was induced by intra-articular injection of MIA, pain behavioral tests were performed. Effects of GFS on the spontaneous activity (SA) were tested with in vivo single-unit recordings from teased fiber saphenous nerve, sural nerve, and dorsal root. RESULTS: Two weeks after intra-articular MIA injection, rats developed pain-like behaviors. In vivo single unit recordings from bundles teased from the saphenous nerve and third lumbar (L3) dorsal root of MIA-OA rats showed a higher incidence of SA than those from saline-injected control rats. GFS at the L3 level blocked L3 dorsal root SA. MIA-OA reduced the punctate mechanical force threshold for inducing AP firing in bundles teased from the L4 dorsal root, which reversed to normal with GFS. After MIA-OA, there was increased retrograde SA (dorsal root reflex), which can be blocked by GFS. CONCLUSIONS: These results indicate that GFS produces analgesia in MIA-OA rats at least in part by producing blockade of afferent inputs, possibly also by blocking efferent activity from the dorsal horn.

Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) decodes neuronal activity by translating cytoplasmic Ca(2+) signals into kinase activity that regulates neuronal functions including excitability, gene expression, and synaptic transmission. Four genes lead to developmental and differential expression of CaMKII isoforms (α, ß, γ, δ). We determined mRNA levels of these isoforms in the dorsal root ganglia (DRG) of adult rats with and without nerve injury in order to determine if differential expression of CaMKII isoforms may contribute to functional differences that follow injury. DRG neurons express mRNA for all four isoforms, and the relative abundance of CaMKII isoforms was γ>α>ß=δ, based on the CT values. Following ligation of the 5th lumbar (L5) spinal nerve (SNL), the ß isoform did not change, but mRNA levels of both the γ and α isoforms were reduced in the directly injured L5 neurons, and the α isoform was reduced in L4 neurons, compared to their contemporary controls. In contrast, expression of the δ isoform mRNA increased in L5 neurons. CaMKII protein decreased following nerve injury in both L4 and L5 populations. Total CaMKII activity measured under saturating Ca(2+)/CaM conditions was decreased in both L4 and L5 populations, while autonomous CaMKII activity determined in the absence of Ca(2+) was selectively reduced in axotomized L5 neurons 21days after injury. Thus, loss of CaMKII signaling in sensory neurons after peripheral nerve injury may contribute to neuronal dysfunction and pain.

Sustained relief of neuropathic pain by AAV-targeted expression of CBD3 peptide in rat dorsal root ganglion.

The Ca(2+) channel-binding domain 3 (CBD3) peptide, derived from the collapsin response mediator protein 2 (CRMP-2), is a recently discovered voltage-gated Ca(2+) channel (VGCC) blocker with a preference for CaV2.2. Rodent administration of CBD3 conjugated to cell penetrating motif TAT (TAT-CBD3) has been shown to reduce pain behavior in inflammatory and neuropathic pain models. However, TAT-CBD3 analgesia has limitations, including short half-life, lack of cellular specificity and undesired potential off-site effects. We hypothesized that these issues could be addressed by expressing CBD3 encoded by high-expression vectors in primary sensory neurons. We constructed an adeno-associated viral (AAV) vector expressing recombinant fluorescent CBD3 peptide and injected it into lumbar dorsal root ganglia (DRGs) of rats before spared nerve injury (SNI). We show that selective expression of enhanced green fluorescent protein (EGFP)-CBD3 in lumbar 4 (L4) and L5 DRG neurons and their axonal projections results in effective attenuation of nerve injury-induced neuropathic pain in the SNI model. We conclude that AAV-encoded CBD3 delivered to peripheral sensory neurons through DRG injection may be a valuable approach for exploring the role of presynaptic VGCCs and long-term modulation of neurotransmission, and may also be considered for development as a gene therapy strategy to treat chronic neuropathic pain.

Painful nerve injury decreases sarco-endoplasmic reticulum Ca²âº-ATPase activity in axotomized sensory neurons.

The sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca(2+) and thereby maintain intracellular Ca(2+) homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca(2+) concentration in traumatized sensory neurons. Here we examine SERCA function in dissociated sensory neurons using Fura-2 fluorometry. Blocking SERCA with thapsigargin (1 µM) increased resting [Ca(2+)](c) and prolonged recovery (τ) from transients induced by neuronal activation (elevated bath K(+)), demonstrating SERCA contributes to control of resting [Ca(2+)](c) and recovery from transient [Ca(2+)](c) elevation. To evaluate SERCA in isolation, plasma membrane Ca(2+) ATPase was blocked with pH 8.8 bath solution and mitochondrial buffering was avoided by keeping transients small (≤ 400 nM). Neurons axotomized by spinal nerve ligation (SNL) showed a slowed rate of transient recovery compared to control neurons, representing diminished SERCA function, whereas neighboring non-axotomized neurons from SNL animals were unaffected. Injury did not affect SERCA function in large neurons. Repeated depolarization prolonged transient recovery, showing that neuronal activation inhibits SERCA function. These findings suggest that injury-induced loss of SERCA function in small sensory neurons may contribute to the generation of pain following peripheral nerve injury.

Subtype-specific reduction of voltage-gated calcium current in medium-sized dorsal root ganglion neurons after painful peripheral nerve injury.

Sensory neurons express a variety of voltage-gated Ca2+ channel subtypes, but reports differ on their proportionate representation, and the effects of painful nerve injury on each subtype are not established. We compared levels of high-voltage activated currents in medium-sized (30-40 µm) dorsal root ganglion neurons dissociated from control animals and those subjected to spinal nerve ligation, using sequential application of semiselective channel blockers (nisoldipine for L-type, SNX-111 or ω-conotoxin GVIA for N-type, agatoxin IVA or ω-conotoxin MVIIC for P/Q-type, and SNX-482 for a component of R-type) during either square wave depolarizations or action potential waveform voltage commands. Using sequential administration of multiple blockers, proportions of total Ca2+ current attributable to different subtypes and the effect of injury depended on the sequence of blocker administration and type of depolarization command. Overall, however, N-type and L-type currents comprised the dominant components of ICa in sensory neurons under control conditions, and these subtypes showed the greatest loss of current following injury (L-type 26-71% loss, N-type 0-51% loss). Further exploration of N-type current identified by its sensitivity to ω-conotoxin GVIA applied alone showed that injury reduced the peak N-type current during step depolarization by 68% and decreased the total charge entry during action potential waveform stimulation by 44%. Isolation of N-type current by blockade of all other subtypes demonstrated a 50% loss with injury, and also revealed an injury-related rightward shift in the activation curve. Non-stationary noise analyses of N-type current in injured neurons revealed unitary channel current and number of channels that were not different from control, which indicates that injury-induced loss of current is due to a decrease in channel open probability. Our findings suggest that diminished Ca2+ influx through N-type and L-type channels may contribute to sensory neuron dysfunction and pain after nerve injury.

ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury.

ATP-sensitive potassium (K(ATP)) channels may be linked to mechanisms of pain after nerve injury, but remain under-investigated in primary afferents so far. We therefore characterized these channels in dorsal root ganglion (DRG) neurons, and tested whether they contribute to hyperalgesia after spinal nerve ligation (SNL). We compared K(ATP) channel properties between DRG somata classified by diameter into small or large, and by injury status into neurons from rats that either did or did not become hyperalgesic after SNL, or neurons from control animals. In cell-attached patches, we recorded basal K(ATP) channel opening in all neuronal subpopulations. However, higher open probabilities and longer open times were observed in large compared to small neurons. Following SNL, this channel activity was suppressed only in large neurons from hyperalgesic rats, but not from animals that did not develop hyperalgesia. In contrast, no alterations of channel activity developed in small neurons after axotomy. On the other hand, cell-free recordings showed similar ATP sensitivity, inward rectification and unitary conductance (70-80 pS) between neurons classified by size or injury status. Likewise, pharmacological sensitivity to the K(ATP) channel opener diazoxide, and to the selective blockers glibenclamide and tolbutamide, did not differ between groups. In large neurons, selective inhibition of whole-cell ATP-sensitive potassium channel current (I(K(ATP))) by glibenclamide depolarized resting membrane potential (RMP). The contribution of this current to RMP was also attenuated after painful axotomy. Using specific antibodies, we identified SUR1, SUR2, and Kir6.2 but not Kir6.1 subunits in DRGs. These findings indicate that functional K(ATP) channels are present in normal DRG neurons, wherein they regulate RMP. Alterations of these channels may be involved in the pathogenesis of neuropathic pain following peripheral nerve injury. Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain.

A supraomohyoidal plexus block designed to avoid complications.

Interscalene blocks of the brachial plexus are used for surgery of the shoulder and are frequently associated with complications such as temporary phrenic block, Horner syndrome or hematoma. To minimize the risk of these complications, we developed an approach that avoids medially directed needle advancement and favors spread to lateral regions only: the supraomohyoidal block. We tested this procedure in 11 cadavers fixed by Thiel's method. The insertion site is at the lateral margin of the sternocleidomastoid muscle at the level of the cricoid cartilage. The needle is inserted in the axis of the plexus with an angle of approximately 35 degrees to the skin, and advanced in lateral and caudal direction. Distribution of solution was determined in ten cadavers after bilateral injection of colored solution (20 and 30 ml) and followed by dissection. In an eleventh cadaver, computerized tomography and 3D reconstruction after radio contrast injection was performed. In additional five cadavers we performed Winnie's technique with bilateral injection (20 and 30 ml). Concerning the supraomohyoidal block the injection mass reached the infraclavicular region surrounded all trunks of the brachial plexus in the supraclavicular region and the suprascapular nerve in all cases. The solution did not spread medially beyond the lateral margin of the anterior scalene muscle into the scalenovertebral triangle. Therefore, phrenic nerve, stellate ganglion, laryngeal nerve nor the vertebral artery were exposed to the injected solution. Distribution was comparable with the use of 20 and 30 ml of solution. Injections on five cadavers performing the interscalene block of Winnie resulted in an extended spread medially to the anterior scalene muscle. We conclude that our method may be a preferred approach due to its safety, because no structures out of interest were reached. Solution of 20 ml is suggested to be enough for a successful block.

Anesthetic effects on mitochondrial ATP-sensitive K channel.

BACKGROUND: Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation. METHODS: Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured. RESULTS: Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation. CONCLUSIONS: Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.

The efficacy of epinephrine or vasopressin for resuscitation during epidural anesthesia.

Cardiopulmonary resuscitation (CPR) during epidural anesthesia is considered difficult because of diminished coronary perfusion pressure. The efficacy of epinephrine and vasopressin in this setting is unknown. Therefore, we designed this study to assess the effects of epinephrine versus vasopressin on coronary perfusion pressure in a porcine model with and without epidural anesthesia and subsequent cardiac arrest. Thirty minutes before induction of cardiac arrest, 16 pigs received epidural anesthesia with bupivacaine while another 12 pigs received only saline administration epidurally. After 1 min of untreated ventricular fibrillation, followed by 3 min of basic life-support CPR, Epidural Animals and Control Animals randomly received every 5 min either epinephrine (45, 45, and 200 microg/kg) or vasopressin (0.4, 0.4, and 0.8 U/kg). During basic life-support CPR, mean +/- SEM coronary perfusion pressure was significantly lower after epidural bupivacaine than after epidural saline (13 +/- 1 vs 24 +/- 2 mm Hg, P < 0.05). Ninety seconds after the first drug administration, epinephrine increased coronary perfusion pressure significantly less than vasopressin in control animals without epidural block (42 +/- 2 vs 57 +/- 5 mm Hg, P < 0.05), but comparably to vasopressin after epidural block (45 +/- 4 vs 48 +/- 6 mm Hg). Defibrillation was attempted after 18 min of CPR. After return of spontaneous circulation, bradycardia required treatment in animals receiving vasopressin, especially with epidural anesthesia. Systemic acidosis was increased in animals receiving epinephrine than vasopressin, regardless of presence or absence of epidural anesthesia. We conclude that vasopressin may be a more desirable vasopressor for resuscitation during epidural block because the response to a single dose is longer lasting, and acidosis after multiple doses is less severe compared with epinephrine.

Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons.

Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I(Ca)) in 101 acutely isolated dorsal root ganglion neurons from 31 rats with neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve, to cells from 25 rats with normal sensory function following sham surgery. Cells projecting to the sciatic nerve were identified with a fluorescent label applied at the CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and conditions designed to isolate I(Ca). Somata of peripheral sensory neurons from hyperalgesic rats demonstrated decreased I(Ca). Peak calcium channel current density was diminished by injury from 3.06+/-0.30 pS/pF to 2. 22+/-0.26 pS/pF in medium neurons, and from 3.93+/-0.38 pS/pF to 2. 99+/-0.40 pS/pF in large neurons. Under these voltage and pharmacologic conditions, medium-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain.

Effects of lidocaine and bupivacaine on isolated rabbit mesenteric capacitance veins.

BACKGROUND AND OBJECTIVES: The direct effects of circulating lidocaine and bupivacaine on splanchnic capacitance veins have not been examined previously. This article reports on the effects of clinically relevant concentrations of lidocaine and bupivacaine on adrenergic responsiveness of isolated rabbit mesenteric veins and examines the mechanism of changes. METHODS: Rings of ileal mesenteric capacitance veins were suspended in tissue baths for isometric tension measurements. Effects of lidocaine and bupivacaine on contractile responses to adrenergic nerve stimulation, exogenous norepinephrine (10(-6) M NE), and potassium chloride (80 mM KCl) were examined in endothelium-intact, L-NAME (10(-4) M) treated or denuded veins. RESULTS: Constriction in response to adrenergic nerve stimulation was attenuated by lidocaine and bupivacaine in a dose-dependent manner, with the potency of bupivacaine being higher than lidocaine. Unstimulated or potassium-constricted veins with and without endothelium were unaffected by lidocaine (0.25-100 microg/mL) and bupivacaine (0.1-100 microg/mL). In veins preconstricted by exogenously administered NE, a cumulative increase of both anesthetics produced no effect at low doses, an augmentation of constriction to NE at 5-20 microg/mL bupivacaine and 20-100 microg/mL lidocaine, and minimal effect at 50-100 microg/mL bupivacaine. These actions persisted in denuded or L-NAME treated veins. Nonincremental delivery of high concentrations of lidocaine or bupivacaine produced relaxation of NE and potassium-constricted rings in the absence and presence of L-NAME. CONCLUSIONS: Lidocaine and bupivacaine in concentrations typical during uncomplicated regional anesthesia inhibit adrenergic neurotransmission in rabbit mesenteric capacitance veins and produce modest venodilatation. Higher doses, resembling concentrations during accidental intravascular injection, result in substantial loss in vasomotor control of these capacitance vessels, which may contribute to hemodynamic effects.

Lumbosacral cerebrospinal fluid volume is the primary determinant of sensory block extent and duration during spinal anesthesia.

UNLABELLED: BACKGROUND. Injection of local anesthetic into cerebrospinal fluid (CSF) produces anesthesia of unpredictable extent and duration. Although many factors have been identified that affect the extent of spinal anesthesia, correlations are relatively poor and the extent of spread remains unpredictable. This study was designed to determine whether variability in the volume of lumbosacral CSF among individuals is a contributing factor in the variability of spinal anesthesia. METHODS: Spinal anesthesia was administered to 10 healthy volunteers with 50 mg lidocaine in 7.5% dextrose. The technique was standardized to minimize variability in factors known to affect the distribution of spinal anesthesia. The extent of sensory anesthesia was assessed by pin-prick and by transcutaneous electrical stimulation. Motor blockade was assessed in the quadriceps and gastrocnemius muscles by force dynamometry. Duration of anesthesia was assessed by pinprick, transcutaneous electrical stimulation, and duration of motor blockade. Lumbosacral CSF volumes were calculated from low thoracic, lumbar, and sacral axial magnetic resonance images obtained at 8-mm increments. Volumes of CSF were correlated with measures of extent and duration of spinal anesthesia using the Kendall rank correlation test. RESULTS: Lumbosacral CSF volumes ranged from 42.7 to 81.1 ml. Volumes of CSF correlated with pin-prick assessments of peak sensory block height (P = 0.02) and duration of surgical anesthesia (as assessed by the duration of tolerance to transcutaneous electrical stimulation at the ankle (P < 0.05). CONCLUSIONS: Variability in lumbosacral CSF volume is the most important factor identified to date that contributes to the variability in the spread of spinal sensory anesthesia.

Effects of desflurane, sevoflurane and halothane on postinfarction spontaneous dysrhythmias in dogs.

BACKGROUND: Although desflurane (DES) and sevoflurane (SEV) have desirable features for use in patients with coronary artery disease, their effects on ventricular dysrhythmias following infarction are less known. We therefore examined the effects of DES and SEV upon spontaneous postinfarction ventricular dysrhythmias in dogs, and compared those effects to the well-established antidysrhythmic effects of halothane (HAL) in this model. METHODS: After institutional approval, the left anterior descending coronary artery was ligated in 16 adult mongrel dogs during isoflurane anesthesia. All dogs developed acute myocardial infarction and severe ventricular tachydysrhythmias. Twenty-two hours after infarction, dogs were anesthetized at 1.5 MAC with desflurane (10.8%) followed by sevoflurane (3.5%) in the treatment group (n = 10), or halothane (1.3%) in the other group (n = 6). Anesthetic gases were allowed to equilibrate for at least 20 min at each end-tidal concentration. At this time, the ECG was recorded for 9 min and evaluated for the number of ventricular ectopic and sinoatrial beats and summed duration of ventricular tachycardia. RESULTS: DES and SEV reduced the average rate of total ventricular ectopic beats by 40 +/- 4% and 42 +/- 4%, respectively. HAL decreased total ventricular ectopic rate by 59 +/- 6% and 62 +/- 5% after durations of anesthesia comparable to DES and SEV, respectively. Decreases in dysrhythmia in the presence of DES and SEV were significantly smaller than those produced by HAL after a comparable total duration of anesthesia. CONCLUSION: DES and SEV inhibit spontaneous postinfarction ventricular dysrhythmias, although attenuation of dysrhythmias was smaller than the inhibition during comparable doses of HAL.

Hypoxia causes apnea during epidural anesthesia in rabbits.

BACKGROUND: Although pulmonary function is minimally changed by neuraxial blockade in most cases, ventilatory arrest may ensue in rare cases. The authors examined the mechanism of apnea in a rabbit model of sudden ventilatory arrest during the combination of epidural anesthesia and hypoxia. METHODS: Rabbits were studied during alpha-chloralose sedation and spontaneous ventilation through a tracheostomy tube. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Respiratory rate and tidal volume were measured by pneumotachograph. Responses were recorded during administration of oxygen at inspired oxygen concentrations of 11% for 2.5 min and 0% for 40 s, before and after either thoracolumbar epidural blockade (0.4 ml/kg lidocaine, 1.5%) or intramuscular lidocaine (15 mg/kg). In a third group of animals, epinephrine was given intravenously during epidural blockade to return mean arterial pressure to baseline values before hypoxia. In a fourth group of animals, which did not get lidocaine, sympathetic blockade and hypotension were produced with intravenously administered trimethaphan rather than epidural blockade. RESULTS: Thoracolumbar epidural anesthesia decreased mean arterial pressure from 76 +/- 4 mmHg (mean +/- SE) to 42 +/- 2 mmHg. Apnea during hypoxia occurred in 90% of these animals (nine of ten) but in only 11% of animals (one of nine) after intramuscularly administered lidocaine (P < 0.01). Treatment of epidural hypotension with epinephrine prevented apnea (zero of nine animals). Apnea during hypoxia occurred in 50% (three of six) of animals given trimethaphan. Apnea in all groups was sudden in onset, with no preceding decreases in respiratory rate or tidal volume. CONCLUSIONS: Epidural anesthesia results in a narrowed margin of safety for oxygen delivery to the brain and predisposes subjects to ventilatory arrest during hypoxia. This results from the combined effects of decreased blood oxygen content, which is due to decreased inspired oxygen concentration superimposed on circulatory depression due to neural blockade.

Effect of thoracic epidural anesthesia on spontaneous postinfarction ventricular dysrhythmia in awake dogs.

BACKGROUND AND OBJECTIVES: Sympathetic neural activity contributes to the genesis of ventricular ectopic activity, particularly in the setting of myocardial ischemia and infarction, so thoracic epidural anesthesia should diminish ventricular ectopy by blocking sympathetic innervation of the heart. However, the possible antidysrhythmic effect of epidural anesthesia has been studied only in the presence of general anesthesia. We therefore examined changes in spontaneous postinfarction ventricular dysrhythmia during thoracic epidural anesthesia in awake dogs. METHODS: A survivable myocardial infarction was created by two-stage ligation of the left anterior descending coronary artery. The following day, multifocal idioventricular tachycardia was the predominant cardiac rhythm. Lidocaine was administered either by thoracic epidural catheter to achieve block of at least the first five thoracic segments or intravenously as a control for direct effects, without concurrent general anesthesia or sedation. Electrocardiographic recordings were analyzed for the number of ventricular ectopic and sinoatrial depolarizations. RESULTS: Epidural and intravenous administration both produced plasma lidocaine concentrations of about 2 mg/mL. There was no change in rhythm following intravenous lidocaine. During epidural anesthesia, total ectopic beats per minute decreased from 167 +/- 8 to 135 +/- 14 (mean +/- SE, P < .05), and the dysrhythmic ratio (ventricular beats/total beats) decreased from 0.93 +/- 0.03 to 0.81 +/- 0.08 (P < .05). However, ventricular tachydysrhythmia remained the predominant rhythm. CONCLUSIONS: Epidural block modestly reduces spontaneous ventricular dysrhythmia in a perioperative setting in dogs following a large myocardial infarction. These findings do not support the choice of thoracic epidural anesthesia for the purpose of preventing or decreasing severe ventricular dysrhythmia.

Neural blockade for diagnosis and prognosis. A review.

On the basis of the published material reviewed above, we conclude that there are many limitations that weaken the theoretic basis for neural blockade as a diagnostic or prognostic tool. In addition, these procedures in general lack thorough documentation of clinical usefulness. Reasonable employment of diagnostic neural blockade, therefore, requires not only care in technique and confirmation of effects, but also caution in interpretation and application of the results. This critical evaluation needs to be tempered, however, by two further observations. Experienced and observant clinicians have found these procedures may, on certain occasions, provide information that is helpful in guiding subsequent therapy, so we should not be in haste to dismiss the accumulated judgment of practitioners. Finally, the confusion and complexity that typifies diagnosis in chronic pain may justify the selective use of diagnostic blocks that make anatomic and physiologic sense, even if their validity is incompletely proved.

Sympathetic and mesenteric venous responses to baroreceptor or chemoreceptor stimulation during epidural anesthesia in rabbits.

BACKGROUND: Baroreceptor and chemoreceptor reflexes maintain homeostasis through mechanisms that involve sympathetic activation. Because sympathetic control of the mesenteric veins plays a central role in hemodynamic responses to stress, the effects of epidural blockade on reflex responses to hypoxia and bilateral carotid occlusion (BCO) were examined by monitoring direct measures of splanchnic sympathetic neural traffic and mesenteric venous capacitance. METHODS: Rabbits were studied during alpha-chloralose anesthesia and mechanical ventilation. Sympathetic efferent nerve activity to the mesenteric vessels was measured by surgically placed electrodes, and mesenteric venous diameter was measured by videomicroscopy. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Intraluminal venous pressure was monitored by a servo-null micropressure technique. Responses were recorded during repeated administration of three different stresses, F1O2 = 0% for 40 s, F1O2 = 11% for 2.5 min, and BCO for 60 s. Animals received either thoracolumbar epidural blockade (0.4 ml/kg lidocaine 1.5%; n = 7) or 15 mg/kg intramuscular lidocaine (n = 7). RESULTS: Hypoxia and BCO produced sympathetic stimulation and active constriction of mesenteric veins. Epidural anesthesia accentuated the mean arterial pressure decrease from F1O2 of 0%, caused the 11% response to F1O2 to become depressor instead of pressor, and decreased the pressor effect BCO. Sympathetic efferent nerve activity and venous diameter responses to hypoxia and BCO were attenuated or eliminated. CONCLUSIONS: The hemodynamic effects of hypoxia result from a combination of direct depression and reflex activation. Thoracolumbar epidural anesthesia in rabbits impairs compensatory reflexes invoked by chemoreceptor stimulation and eliminates response to baroreceptor stimulation. Loss of splanchnic control of mesenteric capacitance contributes to the inhibition of the hemodynamic response to hypoxia or BCO during epidural anesthesia in rabbits.

Neural blockade for upper-extremity pain.

Carefully performed and interpreted neural blockade can be a useful adjunct in both the diagnosis and treatment of painful syndromes of the upper extremity. Pain is a very difficult entity to quantify and diagnose specifically because of its subjective nature, vast differences between patients and their response to pain, and largely because of our inexact understanding of its physiology. Best results of block therapy require thorough understanding of these complexities and limitations, and a rational, careful examination of the data it provides.

Epidural anatomy examined by cryomicrotome section. Influence of age, vertebral level, and disease.

BACKGROUND AND OBJECTIVES: Cryomicrotome section is a means of anatomic examination with minimal artifact ideally suited to delineating details of tissue relationships in the epidural space. In the past, healthy adult lumbar levels have been studied by this method. This report extends observations to other regions of the vertebral column, other age groups, and some abnormal conditions. METHODS: The bodies of 26 adults were frozen in toto soon after death, and the bodies of 2 children were frozen after embalming. Unstained anatomy was revealed by sectioning, and the exposed surface was photographed. RESULTS: As compared with the lumbar level, there are diminished epidural contents at the thoracic and cervical levels, and the ligamentum flavum is more frequently discontinuous. A large basivertebral vein with its origin in the anterior epidural space is typical of the lower thoracic and upper lumbar levels. Although the epidural contents are typically divided into compartments, there is incomplete segmentation of the posterior compartments during early childhood and often at thoracic levels in adults. In advanced age with degenerative disc and joint changes, distortion and compression of the epidural space are typical. CONCLUSIONS: Variations in epidural anatomy due to vertebral level, age, and disease may alter the ease of epidural entry and passage of catheters and injected solution.