Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions.

This paper is an interdisciplinary narrative review of efficacious non-invasive therapies that are increasingly used to restore function in people with chronic spinal cord injuries (SCI). First presented are the secondary injury cascade set in motion by the primary lesion and highlights in therapeutic development for mitigating the acute pathophysiologic process. Then summarized are current pharmacological strategies for modulation of noradrenergic, serotonergic, and dopaminergic neurotransmission to enhance recovery in bench and clinical studies of subacute and chronic SCI. Last examined is how neuromechanical devices (i.e., electrical stimulation, robotic assistance, brain-computer interface, and augmented sensory feedback) could be comprehensively engineered to engage efferent and afferent motosensory pathways to induce neuroplasticity-based neural pattern generation. Emerging evidence shows that computational models of the human neuromusculoskeletal system (i.e., human digital twins) can serve as functionalized anchors to integrate different neuromechanical and pharmacological interventions into a single multimodal prothesis. The system, if appropriately built, may cybernetically optimize treatment outcomes via coordination of heterogeneous biosensory, system output, and control signals. Overall, these rehabilitation protocols involved neuromodulation to evoke beneficial adaptive changes within spared supraspinal, intracord, and peripheral neuromuscular circuits to elicit neurological improvement. Therefore, qualitatively advancing the theoretical understanding of spinal cord neurobiology and neuromechanics is pivotal to designing new ways to reinstate locomotion after SCI. Future research efforts should concentrate on personalizing combination therapies consisting of pharmacological adjuncts, targeted neurobiological and neuromuscular repairs, and brain-computer interfaces, which follow multimodal neuromechanical principles.

Effect of constant light and immobilization stress on rat submandibular saliva secretory response induced by cholinergic and peptidergic agonists

The aim of this work was to analyse the parasympathetic control of submandibular saliva secretory response to cholinergic and peptidergic agonists in rats chronically exposed to constant light or repeated immobilization. Thirty two adult male Wistar rats were used: LL (8 rats exposed to constant light for 20 days), IMO (8 rats submitted to 14:10 h light: dark cycle and immobilized 2 hours daily for 7 days), and control (16 rats not exposed to stress and submitted to 14:10 hours light:dark cycle). Saliva was collected under anesthesia from the salivary ducts of submandibular glands under increasing doses of methacholine and substance P. Secretory responses (µg/saliva/mg dry weight gland) to methacholine were significantly higher in LL and IMO groups compared to control for the following doses (µg/kg body weight): 3 (153±9 versus 46±3, p<0.001 and 76±3 versus 40±3, p<0.001), 10 (379±23 versus 277±8, p<0.001 and 275±19 versus 250±10, p<0.01) and 30 (729±25 versus 695±19, p<0.05 and 1008±39 versus 640±20, p<0.001). Also, responses to substance P were significantly increased in LL and IMO groups compared to control for the following doses: 0.2 (80±3 versus 30±3, p<0.01 and 94±16 versus 31±3, p<0.001), 0.5 (328±20 versus 231±16, p<0.01 and 531±31 versus 219±25,p<0.001), 1 (681±35 versus 547±30, p<0.01 and 1031±63 versus 563±53, p<0.001), and 5 (2222±88 versus 1868±59, p<0.01 and 3230±145 versus 1921±218, p<0.001). In conclusion, supersensitivity of secretory response to both agonists suggests that chronic exposure of rats to stressors capable of activating the sympathetic adrenal system promotes inhibition of the parasympathetic control of salivary secretion.

Anesthetic Considerations for Patients on Antidepressant Therapy-Part I.

Millions of patients take antidepressant medications in the United States for the treatment of depression or anxiety disorders. Some antidepressants are prescribed off-label to treat problems such as chronic pain, low energy, and menstrual symptoms. Antidepressants are a broad and expansive group of medications, but the more common drug classes include tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. A miscellaneous or "atypical" category covers other agents. Some herbal supplements that claim to have antidepressant activity will also be discussed. In Part I of this review, antidepressant pharmacology, adverse effects, and drug interactions with adrenergic agonists will be discussed. In part II, drug interactions with sedation and general anesthetics will be reviewed. Bleeding effects and serotonin syndrome implications in anesthetic practice will also be highlighted.

Estimated Maximal Safe Dosages of Tumescent Lidocaine.

BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction. METHODS: Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUC∞) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 µg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis. RESULTS: In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all <6 µg/mL over the 24-hour study period. AUC∞s with liposuction were significantly less than those without liposuction (P = 0.001). The estimated risk of lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was ≤1 per 2000. CONCLUSIONS: Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a result of delayed systemic absorption, these dosages yield serum lidocaine concentrations below levels associated with mild toxicity and are a nonsignificant risk of harm to patients.

The value of adrenaline in the induction of supraventricular tachycardia in the electrophysiological laboratory.

AIMS: The most commonly used drug for the facilitation of supraventricular tachycardia (SVT) induction in the electrophysiological (EP) laboratory is isoprenaline. Despite isoprenaline's apparent indispensability, availability has been problematic in some European countries. Alternative sympatomimethic drugs such as adrenaline have therefore been tried. However, no studies have determined the sensitivity and specificity of adrenaline for the induction of SVT. The objective of this study was to determine the sensitivity and specificity of adrenaline for the induction of SVT. METHODS AND RESULTS: Between February 2010 and July 2013, 336 patients underwent an EP study for prior documented SVT. In 66 patients, adrenaline was infused because tachycardia was not induced under basal conditions. This group was compared with 30 control subjects with no history of SVT. Programmed atrial stimulation was carried out during baseline state and repeated after an infusion of adrenaline (dose ranging from 0.05 mcg/kgc to 0.3 mcg/kgc). The endpoint was the induction of SVT. Among 66 patients with a history of SVT but no induction under basal conditions, adrenaline facilitated induction in 54 patients (82%, P < 0.001). Among the 30 control subjects, SVT was not induced in any patient (0%) after infusion. Adrenaline was generally well tolerated, except for two patients (3.0%), where it had to be discontinued due to headache and high blood pressure or lumbar pain. CONCLUSION: Adrenaline infusion has a high sensitivity (82%) and specificity (100%) for the induction of SVT in patients with prior documented SVT. Therefore, it could serve as an acceptable alternative to isoprenaline, when the latter is not available.

Does regional compared to local anaesthesia influence outcome after arteriovenous fistula creation?

BACKGROUND: An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis. Unfortunately, approximately one-third of fistulae fail at an early stage. Different anaesthetic techniques can influence factors associated with fistula success, such as intraoperative blood flow and venous diameter. A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone. This, however, has not yet been shown in a large trial to influence long-term fistula patency, the ultimate clinical measure of success.The aim of this study is to compare whether a regional anaesthetic block, compared to local anaesthetic infiltration, can improve long-term fistula patency. METHODS: This study is an observer-blinded, randomised controlled trial. Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet, and consent will be obtained in keeping with the Declaration of Helsinki. Patients will be randomised to receive either: (i) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine, or (ii) local anaesthetic infiltration with lignocaine and levobupivicaine.A total of 126 patients will be recruited. The primary outcome is fistula primary patency at three months. Secondary outcomes include primary patency at 1 and 12 months, secondary patency and fistula flow at 1, 3 and 12 months, flow on first haemodialysis, procedural pain, patient satisfaction, change in cephalic vein diameter pre- and post-anaesthetic, change in radial or brachial artery flow pre- and post-anaesthetic, alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound, and fistula infection requiring antibiotics. CONCLUSIONS: No large randomised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae. If the performance of brachial plexus block increases fistulae patency, this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase, and the number of "redo" or revision procedures should be reduced. TRIAL REGISTRATION: This study has been approved by the West of Scotland Research Ethics Committee 5 (reference no. 12/WS/0199) and is registered with the ClinicalTrials.gov database (reference no. NCT01706354).

Mirabegron: ß3-adrenergic receptor agonist for the treatment of overactive bladder.

OBJECTIVE: To review the place in therapy of mirabegron, a new oral ß3-adrenergic receptor agonist, for the treatment of overactive bladder (OAB). DATA SOURCES: A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-April 2013) was conducted using the key words mirabegron, receptor, adrenergic, beta-3; adrenergic beta-3 receptor; beta-3 receptor, and overactive bladder; urinary bladder; overactive. All published articles regarding mirabegron were included. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, presentations, and clinical trials of mirabegron in humans were reviewed; relevant clinical data were selected and included. DATA SYNTHESIS: Mirabegron is the newest option for treatment of OAB with symptoms of urge incontinence. As a ß3-receptor agonist, it reduces bladder muscle contractions. In two 12-week, randomized, double-blind, placebo-controlled Phase 3 studies, mirabegron significantly reduced the number of incontinence episodes per 24 hours from baseline (-1.47, -1.63, and -1.13; p < 0.05; and -1.57, -1.46, and -1.17; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). Micturitions per 24 hours were also reduced from baseline (-1.66, -1.75, and -1.05; p < 0.05; and -1.93, -1.77, and -1.34; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). A 12-month trial found mirabegron to have a safety and efficacy profile similar to that of tolterodine. CONCLUSIONS: Treatment of OAB initially includes lifestyle and nonpharmacologic intervention; for patients with persistent symptoms despite these treatments, drug therapy represents a next-step approach for symptom control. Mirabegron alleviates symptoms of OAB while having a mechanism of action that provides an alternative for patients who are intolerant of or who have contraindications to anticholinergic agents. The place in therapy of mirabegron relative to anticholinergics in the treatment of urge incontinence has not yet been established.

Hemofiltration with the Cascade system in an experimental porcine model of septic shock.

High-volume hemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock because of its capacities to remove inflammatory mediators from blood. Nevertheless, HVHF presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload due to the frequent changes of large amounts of expensive sterile substitution fluids. A new hemofiltration system called "Cascade" has been developed, allowing very high ultrafiltration rates (120 mL/kg/h) limiting these drawbacks by using a special extracorporeal circuit. The objective of this study was to assess the technical feasibility of the Cascade system and to compare its hemodynamic impact to that of the standard HVHF system. Twenty sepsis-induced pigs were randomized in two groups: one group was hemofiltered with the standard HVHF system and the other with the Cascade system during a six-hour session. No technical problems were observed with the Cascade system during the experiment. At the end of the experiment, colloid requirements (989 +/- 355 mL vs. 1913 +/- 538 mL, P = 0.006), epinephrine requirements (0.82 +/- 0.42 mg vs. 3.27 +/- 3.02 mg, P < 0.001), lactic acidosis (pH = 7.33 +/- 0.08 vs. 7.10 +/- 0.07, P < 0.001) and mean pulmonary arterial pressure were less pronounced in the Cascade group. These results suggest that Cascade hemofiltration is technically feasible and safe. Moreover, compared with standard HVHF, it can reduce the severity of porcine septic shock.

Selective beta blockade improves the outcome of cardiopulmonary resuscitation in a swine model of cardiac arrest.

BACKGROUND AND OBJECTIVES: Epinephrine has been the mainstay drug of choice for cardiac resuscitation for more than 30 years. Its vasopressor effects favoring initial resuscitation point to its beta-adrenergic action. However, its beta-adrenergic actions may have detrimental effects. The aim of the present experimental study was to evaluate the efficiency of coadministration of Esmolol, an ultra-short-acting beta-blocker, and of epinephrine in a swine model of cardiac arrest. MATERIALS AND METHODS: Fourteen pigs (19 +/- 2 Kg) were anesthetized and instrumented. Ventricular Fibrillation (VF) was produced electrically. After induction of VF, the animals were left untreated for 5 minutes. Animals were randomized into two groups, control and study group. Six animals were used in the control group, and 8 in the study group. The control group received 10 ml of normal saline via a peripheral vein, while the study group received 0.4 mg/kg Esmolol in 10 ml dilution. Epinephrine was administered to all animals after the first unsuccessful defibrillation set, and all animals received standardized Advanced Life Support. RESULTS: Seven animals (87.5%) restored cardiac rhythm compatible with a pulse in the Esmolol group, compared to 2 animals (33.3%) in the control group (p = 0.018). The average time until restoration of circulation was 16 +/- 3.2 minutes in our control group and 12.8 +/- 1.4 minutes in Esmolol group (p = 0.059). Coronary perfusion pressure (CPP) was significantly higher in the Esmolol group. CONCLUSIONS: Esmolol improves significantly the outcome of cardiopulmonary resuscitation and the average time of restoration of circulation, while in the proposed dosage does not alter the CPP at the beginning of CPR. However, it augments CPP from the sixth minute of CPR and afterwards.

Nifedipine-sensitive noradrenergic vasoconstriction is enhanced in spontaneously hypertensive rats: the influence of chronic captopril treatment.

AIM: The relationship between increased sympathetic tone and enhanced activity of L-type voltage-dependent Ca2+ channels (L-VDCC) in spontaneously hypertensive rats (SHR) was studied using in vivo and in vitro approaches. METHODS: The effects of acute L-VDCC blockade on sympathetic vasoconstriction or blood pressure (BP) and the contribution of calcium influx to norepinephrine (NE)-induced arterial contraction were investigated in 10-week-old SHR and in age-matched SHR made normotensive by chronic captopril treatment from weaning. RESULTS: Blood pressure fall occurring after acute ganglionic or L-VDCC blockade was enhanced in SHR. Ganglionic blockade eliminated strain differences in BP response to acute L-VDCC blockade and vice versa, suggesting that enhanced contribution of L-VDCC is responsible for augmented sympathetic vasoconstriction in SHR. Both phasic (dependent on internal calcium stores) and tonic (dependent on calcium influx) contractions to NE were augmented in SHR femoral arteries in vitro. Nifedipine attenuated only tonic contractions but to a larger extent in SHR than in WKY arteries. Nifedipine effect was greater after endothelium removal, which augmented tonic but not phasic contractions after NE. Chronic captopril treatment of SHR prevented hypertension development by suppression of their sympathetic vasoconstriction including its nifedipine-sensitive component, but failed to influence enhanced NE-induced arterial contractions or increased relaxation to nifedipine in vitro. CONCLUSION: The contribution of nifedipine-sensitive component to noradrenergic vasoconstriction is enhanced during excessive NE stimulation (increased sympathetic tone of SHR in vivo or supramaximal NE stimulation in vitro). It seems that captopril-induced reduction of central sympathetic tone is able to normalize augmented nifedipine-sensitive vasoconstriction in SHR.

Anaphylaxis to foods.

Three crucial areas of the management of anaphylaxis due to food allergy are discussed: making a diagnosis, deciding who needs a self-injectable adrenaline device and spotting the novel allergen. Managing children and teenagers with anaphylaxis is challenging due to the lack of available evidence that specific addresses these issue. The available evidence is presented and discussed.

Effect of Thymol on the spontaneous contractile activity of the smooth muscles.

Effects of Thymol on the spontaneous contractile activity (SCA) have been found in in vitro experiments with circular smooth-muscle strips (SMAs) from guinea pig stomach and vena portae. Thymol was found to possess an agonistic effect on the alpha(1)-, alpha(2)- and beta-adrenergic receptors. Its spasmolytic effect is registered at doses higher than 10(-6)M. Thymol in a dose of 10(-4)M inhibits 100% the SCA of the SMAs and reduces the excitatory effect of 10(-5)M ACH to 35%. It is assumed that Thymol has an analgesic effect through its action on the alpha(2)-adrenergic receptors of the nerve cells. By influencing the beta-adrenergic receptors in the adipose cells, it is possible to induce increased synthesis of fatty acids and glycerol, which is a prerequisite for increased heat release.

Efeitos hemogasométricos da xilazina e da romifidina em cabras tratadas por ioimbina / Haemogasometric effects of xylazine and romifidine in goats treated with yohimbine

Estudaram-se as alterações produzidas por doses equipotentes de xilazina e romifidina e os efeitos da administração subseqüente de ioimbina em oito cabras mestiças. Respeitou-se um intervalo de sete dias entre os seguintes tratamentos: A- 250µg/kg/IM de xilazina e 0,1ml/kg/IV de solução fisiológica, B- 250µg/kg/IM de xilazina e 250µg/kg/IV de ioimbina, C- 25µg/kg/IM de romifidina e 0,1ml/kg/IV de solução fisiológica, D- 25µg/kg/IM de romifidina e 250µg/kg/IV de ioimbina. Foram mensurados a freqüência respiratória, o pH, as pressões parciais de oxigênio e dióxido de carbono, a concentração de íon bicarbonato, o excesso de bases e a saturação de oxigênio no sangue arterial. Utilizou-se um delineamento experimental crossover, e as médias foram comparadas pelo teste Duncan (Pmenor ou igual a 0,05). Xilazina e romifidina reduziram a pressão arterial de oxigênio e aumentaram a pressão arterial de dióxido de carbono. A ioimbina reverteu os efeitos da xilazina e da romifidina sobre as pressões parciais de oxigênio e dióxido de carbono no sangue arterial.

Histaminergic effect of crude papaya latex on isolated guinea pig ileal strips.

In the present study, we investigated the effect of the crude latex of Carica papaya L. (CPX) on isolated guinea pig ileal strips. CPX (0.5-512 microg/ml) caused concentration-dependent contraction of ileal strips suspended in Tyrode solution. The concentration of atropine (0.69 microM) that significantly blocked the contractile effect of acetylcholine on the isolated guinea pig ileum showed no significant effect on CPX- and histamine-induced contractions of the ileal strips. Mepyramine (87.6 nM) significantly blocked the contractile effect of histamine and CPX on the ileum. The same concentration of mepyramine, however, had no significant effect on acetylcholine-induced contraction of the isolated ileal strips. Removal of Ca2+ from the bathing medium abolished ileal contractions induced by acetylcholine, histamine and CPX. All the test substances were able to provoke ileal contractions after replacement of the Ca(2+)-free solution with Tyrode solution. Furthermore, 10(-5) M of nifedipine, a Ca(2+)-entry antagonist, reversibly inhibited the contractile effect of all the test substances on the ileal strips. Results of this study together appear to show that CPX-induced contraction of the isolated guinea pig ileum is mediated via H1-receptors and dependent on extracellular Ca2+ influx.

Local anaesthetic endonasal endoscopic laser dacryocystorhinostomy: analysis of patients' acceptability and various factors affecting the success of this procedure.

BACKGROUND AND OBJECTIVES: Endonasal endoscopic laser dacryocystorhinostomy is now a well established, effective approach to relieve nasolacrimal duct obstruction. Whereas attempts have been made to comment on the efficacy of the procedure, no study has been conducted to evaluate the acceptability of this procedure by those at the receiving end, ie, the patients. An attempt has been made in the present study to critically evaluate the procedure from the point of view of patients' acceptability and also to evaluate certain factors which may influence the success rate of this procedure. PATIENTS AND METHODS: Forty-six eyes from 40 patients underwent endonasal endoscopic laser dacryocystorhinostomy, performed by the same surgeon, over a period of 15 months. Various aspects of the procedure were evaluated by patients by filling out a simple questionnaire (Figure 1). In addition to recording patients' views, success of the procedure was confirmed by performing a postoperative sac washout in the clinic. Patients were also subdivided according to their age, duration of symptoms and history of previous surgical intervention. The data were statistically analysed using chi-square tests with the Yates correction. RESULTS: The percentage of patients who declared themselves completely cured was 65.22%. A partial resolution was felt by 23.91% of patients and no improvement was reported by 10.87% of patients. Forty-two out of the 46 eyes (91.3%) achieved anatomical success by the procedure, as shown by a postoperative sac washout performed in the clinic. Some of them, however, did not have complete resolution of their symptoms perhaps due to an additional factor of lacrimal pump dysfunction in these patients. During the procedure 60.86% of eyes felt no discomfort at all whereas 39.14% of eyes felt some discomfort at some point of time during the procedure (Table 1). When directly asked 86.12% of patients recommended the procedure (implying that the procedure had some good effect on their quality of life), 8.33% of patients did not recommend it and 5.55% of patients made no comments. Various factors affecting the success of this procedure were analysed (Table 2) and it was found that eyes which had no previous surgical intervention showed a complete cure rate which was significantly higher than that seen in eyes which had some sort of previous intervention (P = 0.0003); eyes with a short (<6 mths) duration of symptoms showed significantly higher success rates (P = 0.0098) in comparison to that shown by eyes with longer (>6 mths) duration of symptoms; and younger patients (<50 yrs) had a complete resolution rate much higher than patients over 50 yrs of age (P = 0.0309). CONCLUSION: The present study clearly shows that endonasal endoscopic laser DCR is an effective procedure, well tolerated and recommended by the patients. Discomfort during the procedure is not a major problem. Younger patients, with no previous surgical intervention and with short duration of symptoms are likely to be benefited the most. Though success rates are higher with external DCR, endonasal endoscopic laser DCR offers certain advantages over the external approach while keeping the option of external DCR open, if needed at a later date.

Sympathetic innervation of mammary glands mediates suckling-induced reflex inhibition of milk yield in rats.

Previous work has shown that physiologic activation of the sympathetic system may inhibit milk yield (ME) in rats. Thus, adrenal catecholamines (CAs) are released by suckling, but it is not known whether such inhibition results also from reflex activation by the same stimulus of neural sympathetics upon the mammary gland. The present experiments were designed to determine whether suckling inhibits ME induced by oxytocin (OT) in the urethane-anesthetized lactating rat, and whether such inhibition results from adrenal and/or neurally released CAs. Rats were isolated (6 h) from their pups and then anesthetized. OT (0.8 mU every 2 min) was administered intravenously to the mothers during suckling. Rats were either chronically implanted with cannulae into the lateral cerebral ventricles (intracerebroventricularly), bilaterally adrenalectomized (ADX), hypophysectomized (HX), spinal cord transected (SCT: T3-T4), or had the nipple area (NA) locally anesthetized before suckling. MEs were low in control, sham, ADX and HX rats, but not in rats given the beta-adrenergic blocker propranolol (PROP; intravenously or intracerebroventricularly injected), nor in SCT, NA or PROP-HX rats. As revealed by ductal resistance measurements as an indicator of ductal tone, suckling-induced inhibition of ME was due to ductal constriction within the mammary glands. These effects of suckling, however, could be prevented by prior activation of ductal mechanoreceptors. Together, these results indicate that suckling inhibits ME through the reflex activation of neurally mediated central beta-adrenergic mechanisms, and that these effects, in turn, can be regulated by ductal mechanoreceptor activation.

Comparison of transarterial and multiple nerve stimulation techniques for axillary block using a high dose of mepivacaine with adrenaline.

BACKGROUND: High-dose transarterial (TA) technique results in high effectiveness of the axillary block. The technique is fast and simple, but does not produce a satisfactory success rate when using the manufacturer's recommended dose of mepivacaine. The multiple nerve stimulation (MNS) technique requires more time and experience. This double-blind study compared effectiveness, safety and the time used to obtain an effective analgesia in 101 patients, having an axillary block by either TA or MNS techniques. METHODS: Mepivacaine with adrenaline (MEPA), 850 mg, was used for the initial block. Five millilitres of 1% solution was injected subcutaneously. In the TA group, 20 mL of 2% solution was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and, when needed, supplemented after 30 min. The block was effective when analgesia was present in all sensory nerve areas distal to the elbow. RESULTS: The MNS group required median 11 min for block performance compared with 8 min for the TA group (P < 0.001). Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (median 10 min and 6%) than in the TA group (30 min and 36%, respectively), P < 0.001. All incomplete blocks were successfully supplemented. However, the total time to obtain an effective block was shorter in the MNS group (23 min) than in the TA group (37 min), P < 0.001. Two patients in each group had signs and symptoms of systemic toxicity, the most serious being atrial fibrillation and temporary loss of consciousness in a cardiovascularly medicated patient. The local adverse effects (intravascular injections and haematomas) were fewer in the MNS group, P < 0.001. CONCLUSION: The MNS technique of axillary block by four injections of 10 mL of 2% MEPA produces faster and more extensive block than the TA technique by two injections of 20 mL. Therefore, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery. However, high doses of MEPA may result in dangerous systemic toxic reactions.

Pre-incision infiltration with lidocaine reduces pain and opioid consumption after reduction mammoplasty.

BACKGROUND AND OBJECTIVES: To determine the analgesic efficacy of preoperative tumescent infiltration with lidocaine for reduction mammoplasty. METHODS: Women with mammary hypertrophy were randomly allocated to one of two study groups in a double-blind clinical trial. Patients in group 1 received preincision infiltration with 5 mL/kg of 0.35% lidocaine with 1:1,000,000 epinephrine into each breast after induction of general anesthesia. Group 2 patients received similar injections of 5 mL/kg of saline with 1:1,000,000 epinephrine. Intravenous patient-controlled analgesia (PCA) morphine (1.0 mg bolus with 5-minute lockout) was available for 9.5 hours in the postoperative period. Visual analog pain scores were recorded during the postoperative period, and hourly morphine consumption data were retrieved from the PCA apparatus. Fitness for discharge was evaluated by the postanesthesia care unit nurse using standardized discharge criteria. RESULTS: Visual analog pain scores were higher in group 2 patients until 3.5 hours after surgery. Patients in the saline group had higher intravenous morphine consumption during all 1-hour postoperative intervals, although the differences between groups were statistically significant only until 4.5 hours after the operation. Total intravenous morphine consumption during the first 9.5 hours after surgery in group 1 was 16.9+/-11.9 mg versus 31.1+/-18.0 mg in group 2 (P < .05). Postoperative nausea and vomiting occurred with equal frequency (87%) in both study groups, and there was no difference between groups in time to achieve fitness for discharge, i.e., a postanesthesia discharge score of > or = 9. CONCLUSION: Preoperative tumescent infiltration with lidocaine results in reduced pain and lower postoperative opioid requirements in the initial hours after reduction mammoplasty.

Epinephrine prolongs duration of subcutaneous infiltration of local anesthesia in a dose-related manner. Correlation with magnitude of vasoconstriction.

BACKGROUND AND OBJECTIVES: Epinephrine is frequently combined with local anesthesia to prolong analgesia. Determination of the minimal concentration and the dose of epinephrine that produces prolongation of analgesia is important in the face of epinephrine's potential for systemic and local toxicity. The authors undertook this study to determine a dose-response curve of epinephrine on duration of analgesia of both 1% lidocaine and 0.25% bupivacaine after local infiltration. In order to determine whether epinephrine-induced vasoconstriction affected duration of analgesia, the authors correlated duration of analgesia with magnitude of local vasoconstriction as measured with laser Doppler flowmetry. METHODS: Six volunteers were studied in a randomized double-blind manner. Ten skin wheals of 0.2 mL solution were subcutaneously injected into both forearms of each volunteer. The solutions consisted of 1% lidocaine with epinephrine concentrations of 0, 1:50,000, 1:200,000, 1:800,000, and 1:3,200,000, and 0.25% bupivacaine with the same epinephrine concentrations. Duration of loss of sensation to pinprick at each wheal was recorded. Skin wheals with 0.2 mL of these same solutions were also subcutaneously injected into the abdomen of the same 6 volunteers, and laser Doppler flowmetry readings of skin blood flow were measured for 6 hours after injection. RESULTS: Epinephrine prolonged duration of analgesia for both lidocaine and bupivacaine in a dose-related manner (P < .001). All concentrations of epinephrine attenuated the vasodilation observed in the first 15 minutes after injection with plain local anesthesia (P = .03), and blood flow returned to baseline by 30 minutes after injection of either plain or epinephrine-containing solutions. Duration of analgesia correlated with magnitude of vasoconstriction only at the 15-minute measurement (r = .53 and .57, P = .003 and 0.001 for lidocaine and bupivacaine, respectively). CONCLUSIONS: Epinephrine prolongs duration of analgesia after local infiltration in a dose-related manner. Addition of epinephrine in concentrations of 1:50,000 or 1:200,000 increases duration of analgesia after local infiltration by approximately 200%. Addition of doses as dilute as 1:3,200,000 still increases duration of analgesia by approximately 100%. Duration of analgesia appears to correlate with magnitude of epinephrine-induced vasoconstriction using laser Doppler flowmetry. Based on study data, the use of epinephrine in concentrations from 1:200,000 to 1:3,200,000 is recommended for prolongation of analgesia after local infiltration.

[Pharmacological correction of stress reactions after hyperthermia]. / Farmakologicheskaia korrektsiia stressovoi reaktsii pri gipertermii.

It was demonstrated experimentally that aminazine, phentolamine, nuredal, sapilent, teperin, dopegyt improved significantly the health status of animals exposed to high temperature and in many cases prevented their death. This gives evidence that the sympathetic nervous system plays a leading role in heat stroke and that sympathotrophic drugs can be used for protective purpose during acute overheating.