Aneurysmal subarachnoid haemorrhage (aSAH) is associated with high morbidity and mortality despite novel treatments. Genetic variability may explain outcome differences. Apolipoprotein E (ApoE) is a glycoprotein with a major role in brain lipoprotein metabolism. It has three isoforms encoded by distinct alleles: APOEε2, APOEε3 and APOEε4. The APOEε4 allele is associated with Alzheimer's disease and worse outcome after traumatic brain injury and ischaemic stroke. This prospective blinded study explored the influence of the APOEε4 polymorphism on the risk of aSAH, risk of cerebral vasospasm (CVS) and 1-year neurological outcome.The APOΕε4 polymorphism was analysed in 147 patients with aSAH. Allele and genotype frequencies were compared to those found in a gender- and area-matched control group of healthy individuals (n = 211). Early CVS was identified and treated according to neurointensive care unit (NICU) guidelines. Neurological deficit(s) at admittance and at 1-year follow-up visit was recorded. Neurological outcome was assessed by the National Institute of Health Stroke Scale, Barthel Index and the Extended Glasgow Outcome Scale.APOEε4 and non-APOEε4 allele frequencies were similar in aSAH patients and healthy individuals. The presence of APOEε4 was not associated with the development of early CVS. We could not find an influence of the APOE polymorphism on 1-year neurological outcome between groups. Subgroup analyses of patients treated with surgical clipping vs endovascular coiling did not reveal any associations.The APOEε4 polymorphism has no major influence on risk of aSAH, the occurrence of CVS or long-term neurological outcome after aSAH.

Objective: We investigated if tau, microtubular binding protein, in serum and ventricular CSF (vCSF) in patients with severe traumatic brain injury (TBI) during the initial posttraumatic days correlated to 1-year outcome. Methods: Patients with severe TBI (n = 39, Glasgow Coma Scale score <= 8) were included. We measured serum and vCSF total tau on days 0 to 14, using ELISA. vCSF total tau correlated to 1-year Extended Glasgow Outcome Scale (GOSE), the NIH Stroke Scale (NIHSS) neurologic status, and the Bartel Daily Living Index. Patients (n = 20) with normal pressure hydrocephalus (NPH) served as reference. Results: Higher levels of tau were found in TBI patients vs patients with NPH. A correlation was found between initial vCSF total tau and GOSE levels (R = 0.42, p < 0.001) but not between vCSF total tau and NIHSS or Bartel scores at 1 year. A vCSF total tau level of > 2,126 pg/mL on days 2 to 3 discriminated between dead and alive ( sensitivity of 100% and a specificity of 81%). A vCSF total tau level of > 702 pg/mL on days 2 to 3 discriminated between bad ( GOSE 1 to 4) and good ( GOSE 5 to 8) outcome ( sensitivity of 83% and a specificity of 69%). Patients with GOSE 1 (dead) had higher vCSF total tau levels on days 2 to 3 (p < 0.001) vs both surviving patients (GOSE 2 to 8) and those with NPH. Total tau was not detected in serum throughout the study. Conclusion: The increase in ventricular CSF (vCSF) total tau probably reflects axonal damage, known to be a central pathologic mechanism in traumatic brain injury ( TBI). These results suggest that vCSF total tau may be an important early biochemical neuromarker for predicting long-term outcome in patients with a severe TBI.

Background: Small-bowel obstruction is characterized by accumulation of fluid in the obstructed intestine. A pronounced inflammation in the obstructed gut wall has been shown to play an important role in the pathogenesis of the profuse fluid losses. alpha-Trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) has potent anti-inflammatory as well as antisecretory properties. The effects of alpha-Trinositol on inflammation and fluid losses in the obstructed small intestine are. examined. Methods: A total obstruction of the proximal part of the rat jejunum was induced during 18 h by thread ligation. A small segment of the obstructed intestine, with intact vascular and nervous supply, was placed in a chamber suspended from a force displacement transducer allowing for continuous registration of net fluid transport on a Grass polygraph. Three groups were included. One group (n = 12) received low-dose alpha-Trinositol (bolus: 2 mg kg(-1); IV infusion: 10 mg kg(-1) min(-1)), a second group (n = 10) received high-dose alpha-Trinositol (bolus: 12 mg kg(-1); IV infusion: 60 mg kg(-1) min(-1)), while a control group (n = 9) received corresponding volumes of isotonic saline (bolus: 0.5 ml; IV infusions 15 mul min(-1)). Quantitative measurement of extra-vasated Evans blue albumin in the obstructed jejunum was used as a marker of inflammation. Results: High-dose alpha-Trinositol induced a significant (P < 0.001) inhibition of net fluid secretion, while low-dose &alpha;-Trinositol had no significant effect versus saline. In contrast, both doses of &alpha;-Trinositol induced significant inhibition of EB-albumin leakage (P < 0.05). Conclusion: High-dose alpha-Trinositol is a potent inhibitor of fluid secretion in obstructive ileus, most probably involving an anti-inflammatory mechanism.

Amide local anaesthetics have previously been shown to reduce oedema and improve dermal perfusion following experimental burns. Previous studies have used invasive techniques for burn oedema quantification which do not allow continuous monitoring in the same animal. The present study used digital image colour analysis to investigate the effect of topical local anaesthetics on burn-induced extravasation of Evans blue albumin. A standardised full-thickness burn injury (1 × 1 cm) was induced in the abdominal skin of anaesthetised rats. The burn area was subsequently covered with 0.5 g of lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA®, ASTRA, Sweden) or placebo cream during the first hour post-burn. One hour after the burn trauma, animals received Evans blue dye intravenously. Skin colour appearances were recorded by macrophotography before the burn and 5, 60, 65, 90, 120, 150, and 180 min post-burn. Colour slides were digitised and colour changes were analysed using the normalised red-green-blue (n-rgb) colour system. Results showed a significant inhibition of Evans blue extravasation between 60 and 180 min post-burn in EMLA®-treated animals versus controls. Topical local anaesthetics are potent inhibitors of burn-induced plasma albumin extravasation, probably by direct action on vascular permeability and by inhibition of various steps of the pathophysiological response after burn injury.

Deep partial-thickness burn injury was induced in the abdominal skin of anesthetized rats. Dermal perfusion was assessed by laser Doppler flowmetry. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g) for 6 hours, starting 5 minutes after inducing the burn injury. In one control group (n = 14), the thermal injury was treated with placebo cream. Results showed a markedly reduced perfusion in the skin of the control animals within the first hour after burn injury, with further decrease during the following 5 hours of observation. In animals treated with the lidocaine-prilocaine cream, skin perfusion in the burned area was significantly increased during the first 30 minutes after the burn injury compared to before the burn (p < 0.01), followed by a decrease to a level below the preburn stage but significantly higher than that of control animals during the first hour after burn injury (p < 0.05). As opposed to burned control animals, skin perfusion gradually recovered toward preburn levels at the end of the experiment in local anesthetic-treated animals. In the second experimental set, four groups of animals were burned and subsequently treated with a bolus dose of lidocaine intravenously (2 mg/kg), followed by continuous intravenous lidocaine infusions at a rate of 50 (n = 10), 100 (n = 11), or 150 (n = 10) micrograms.kg-1.min-1. The infusions were started 5 minutes after the burn injury and lasted for 6 hours. Corresponding volumes of saline solution were given to burned control animals (n = 10). Results showed a significantly improved skin perfusion in the lidocaine-treated group in a dose-response fashion as compared to control animals. A maximum improvement of dermal perfusion in the burned area was induced by intravenous lidocaine at an infusion rate of 150 micrograms.kg-1.min-1 as compared to burned controls treated with isotonic saline solution infusions (p < 0.01). Results showed that topical or systemic administration of local anesthetics can prevent progressive dermal ischemia after thermal injury.

BACKGROUND:The profuse fluid losses and morbidity of patients suffering from obstructive ileus are closely related to inflammatory changes in the obstructed bowel wall. Previous experimental studies have shown that use of steroids and NSAIDs can reduce fluid losses in obstructive ileus. In the present study, we investigated the effects of lidocaine on fluid losses since local anesthetics have been shown to possess wide and potent anti-inflammatory properties. Hexamethonium and atropine were used to study the importance of the autonomic nervous system in bowel obstruction.METHOD:Experiments were performed in rats in vivo. After 18 h of total obstruction of the jejunum by thread ligation, a segment of the obstructed jejunum was placed in a chamber with intact nervous and vascular supply and net fluid transport was continuously registered by a gravimetric technique. Extravasation of Evans blue albumin as marker of inflammation was quantified by spectrophotometry.RESULTS:Hexamethonium (10 mg.kg-1 i.v.) significantly inhibited net fluid secretion (P < .05), while atropine (0.25 mg.kg-1 i.v.) had no significant effect. Net fluid secretion was reversed into absorption following an intravenous bolus dose of lidocaine (2 mg.kg-1) (P < 0.01) and topical administration of lidocaine (20 mg) on the serosa of the obstructed gut (P < 0.01). Single topical administration of lidocaine (20 mg) immediately before ligation significantly reduced net fluid secretion (P < 0.05) and inflammation (P < 0.05) in the obstructed bowel 20 h post-ligation compared to obstructed controls.CONCLUSION:Lidocaine significantly inhibited or prevented fluid losses when administered intravenously or topically to the obstructed gut. Mechanisms of action could be inhibition of nerve reflexes involved in fluid secretion and by inhibition of inflammation in the bowel wall. The inhibition of fluid losses by hexamethonium further supports the importance of the autonomic nervous system in the pathophysiology of bowel obstruction.

Abstract: Small-bowel obstruction (SBO) is a serious condition induced by hindrance of the propagation of intestinal contents. Mortality of 5% is still relatively high, but has decreased since the beginning of this century when it was around 60%. The condition is characterized by severe abdominal pain, accumulation of gas and fluids in the obstructed intestine and dehydration of the patient. The mechanisms responsible for the profuse fluid losses remain unclear. The aim of this thesis was to elucidate some aspects of the pathophysiology by using an experimental in vivo model in rats. In anaesthestized animals jejunum was ***string-ligated approximately 10 cm distal of the ligament of Treitz. The laparotomy was closed and the animals allowed to recover. Next day the animals were reanaesthetized, tracheostomy was performed and the femoral artery and vein catheterized. Complete obstruction of the jejunum during 18 h resulting in fluid secretion which was subsequently measured using a gravimetric technique allowing continuous registration of intestinal net fluid transport (NFT). After a control period of 30 min with stable net fluid secretion drugs or saline were administered. Mean NFT of the following 2 h was compared to the mean NFT of the control period. In some animals Evans blue dye (20 mg · kg −1 ) was given as marker of blood vessel permeability. Some aspects of the study were investigated in human gastrointestinal tissue. Results show that a pronounced inflammation occurs in the obstructed bowel wall, as suggested by extravasation of plasma Evans blue-albumin visualized by fluorescence microscopy and quantified by spectrophotometry. This was paralleled by net fluid secretion in the obstructed intestine. The importance of inflammation for the mechanisms of fluid losses was illustrated by the actions of the anti-inflammatory agents, hydrocortisone and indomethacin, which reversed secretion into net fluid absorption. We proposed that the inflammation-induced secretion of SBO was partly mediated through the enteric nervous system (ENS). This is supported by results showing that lidocaine, a local anaesthetic, with anti-inflammatory properties, inhibited both inflammation and secretion, and anti-inflammatory action of lidocaine was also shown in a human model where it reduced release of prostaglandins. The importance of ENS was further supported by results showing that the neurotransmitters vasoactive intestinal peptide (VIP) and somatostatin are involved in the regulation of fluid transport. VIP antiserum significantly reduced the net secretion, while the somatostatin analogue octreotide reversed net secretion into net absorption. Octreotide, which inhibits the release of many peptides including VIP, also reduced the Evans blue-albumin extravasation. The secretion of SBO was also shown to be under influence of the sympathoadrenal system since clonidine, an α 2 -adrenoceptor agonist, and propranolol, a β-adrenoceptor antagonist, inhibited net fluid secretion. There were no significant effects on NFT after administration of α 1 - or β 1 -adrenoceptor agonists or antagonists. In conclusion, the present work shows that obstruction of the small intestine will induce a pronounced inflammatory reaction in the bowel wall, most prominent in the external muscle layer. This inflammation probably triggers the profuse fluid losses by direct action on the enterocytes and by activation of enteric neurons. The anti-inflammatory agents hydrocortisone, indomethacin, lidocaine and octreotide significantly reduced both the fluid losses and the increased Evans blue-albumin extravasation. Neuropeptides of the ENS are also important, and neutralization of VIP using VIP antiserum or inhibiting the release of VIP by octreotide both reduced fluid losses. The fluid transport in obstructed gut seems also to be under tonic control of adrenergic neurons, as stimulation of α 2 -adrenoceptors and blockade of β 2 -adrenoceptors reduced fluid losses, while blockade of α 2 -adrenoceptors and stimulation of β 2 -adrenoceptors increased the net fluid secretion. Treatment of patients with small bowel obstruction with anti-inflammatory drugs may prove beneficial

d-myo-Inositol-1,2,6-trisphosphate (IP3) has been shown to reduce edema and progressive ischemia following experimental skin burns. The mechanism(s) are not identified but could be related to antiinflammatory effects of the agent. In the presentex vivostudy we compared the effects of IP3with those of saline and indomethacin on eicosanoid formation by normal and burned rat skin. In burned skin IP3treatment reduced the release of thromboxane B2(TXB2) (P< 0.01) and leukotriene B4(LTB4) (P< 0.05) but there was only a weak trend for less prostaglandin E (PGE) compared to burned control animals receiving saline. Indomethacin reduced the release of TXB2(P< 0.01), and PGE (P< 0.001), but not LTB4from burned skin compared to skin from saline-treated burned animals. In nonburned skin IP3increased the release of PGE (P< 0.01) and LTB4(P< 0.01), but did not significantly influence TXB2accumulation in the incubation fluid compared to the saline-treated group. Indomethacin reduced the release of TXB2(P< 0.001) and PGE (P< 0.001), but increased LTB4(P< 0.001) in normal skin compared to the saline-treated group. In conclusion, IP3inhibited the release of TXB2and LTB4from burned skinex vivo,but increased PGE and LTB4release from normal skin. These results suggest that the mode of action of IP3differs from that of nonsteroidal antiinflammatory drugs. The effects of IP3on the arachidonic acid cascade also seem to differ in burned versus normal skin.

Background: Previous observations have shown vasoactive intestinal peptide (VIP) to be an important secretagogue in the gut, whereas somatostatin has been reported to inhibit VIP release and fluid secretion. Methods: The possible role of VIP as mediator of the inflammation and fluid losses in obstructive ileus was investigated in vivo in a chronic rat model with thread ligation of the jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by spectrophotometry. Net fluid secretion was measured by a gravimetric technique. VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin analogue, octreotide, was used to inhibit the release of VIP. Results: Results showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum (p < 0.05). Net fluid secretion in control animals remained constant. Conclusions: These findings suggest that VIP is an important mediator of the pathophysiology in mechanical intestinal obstruction and that somatostatin may be involved in the endogenous control of fluid losses.

Objectives: To investigate the importance of adrenoceptors on fluid losses in small bowel obstruction. Design: Evaluation of the effects of adrenergic agonists and antagonists on in-vivo net fluid secretion in chronic small bowel obstruction in rats. Methods: Net fluid transport in a jejunal segment was continuously registered in vivo after 18 h of mechanical obstruction of the small bowel in anaesthetized rats. The effect on net fluid transport of adrenoceptor agonists and antagonists and of isotonic saline was quantified. Results: Clonidine, an α2-agonist, had a significant (P<0.05) anti-secretory effect, while yohimbine, an α2-antagonist, significantly (P<0.05) increased net fluid secretion. Phenylephrine, an α1-agonist, and prazosin, an α1-antagonist, lacked significant effects on net fluid transport. Similarly, prenalterol, a β1-agonist, and metoprolol, a β1-antagonist, had no significant effect on the net fluid transport. The β2-agonist salbutamol significantly (P<0.001) increased net fluid secretion, while the β-antagonist propranolol significantly (P<0.001 ) decreased net fluid secretion. Conclusion: Activation of α2-adrenoceptors and blockade of β2-adrenoceptors significantly reduce net fluid secretion in small bowel obstruction. Results also demonstrate a continuous stimulatory effect on fluid secretion mediated by β2-receptors and a continuous inhibitory effect mediated by α2-receptors.

Lignocaine can affect prostaglandin synthesis in various tissues, and it has anti-inflammatory activity. No studies have been made previously on human isolated gut tissues. When concentrations of 5, 50 and 250 mu g mL(-1) lignocaine were incubated with human gastric mucosa/submucosa at 37 degrees C for 30 min, only the highest concentration reduced the levels of prostaglandin E, thromboxane B-2 and 6-keto-PGF(1 alpha), in the incubates, and leukotriene C-4/D-4 was unaffected. Therapeutically relevant amounts of lignocaine given parenterally would therefore seem unlikely to alter gastric mucosal prostanoids, but high doses can be given orally because of extensive first-pass metabolism in the liver.

We investigated the effects of adrenergic, cholinergic and vasoactive intestinal polypeptide (VIP)-ergic agonists and antagonists on the amplitude of gastric phasic contractions in the anaesthetized rat using a volumetric model. The amplitude of the phasic contractions was reduced significantly by atropine, hexamethonium or bilateral cervical vagotomy indicating that cholinergic neural activity involving both muscarinic and nicotinic receptors and intact vagal nerve function are integral parts of the control of basal gastric phasic motility. In contrast, neither selective alpha 1-, alpha 2- or non-selective beta-blockers had any significant influence on the amplitude of the gastric contractions suggesting that adrenergic neurones are not tonically active in the maintenance of basal phasic motility in the stomach. The amplitude of the gastric phasic contractions was, however, significantly reduced by the alpha 1-agonist L-phenylephrine, the alpha 2-agonist clonidine and a close intraarterial injection of VIP (3 micrograms kg-1) but not be the selective beta 1-agonist, prenalterol, or the beta 2-agonist, salbutamol. These data suggest the presence of superimposed inhibitory control of phasic activity by VIP-ergic stimulation and by adrenergic neurones via alpha-receptor stimulation.

The importance of inflammation for fluid losses in obstructive ileus was investigated in vivo in the rat. Inflammation was quantified by spectrophotometry of extravasated Evans blue (Eb)-albumin. Net fluid secretion in the obstructed jejunum was measured by a continuous gravimetric technique. The inflammation in the obstructed gut wall was significantly more pronounced than that in the gut distal to the obstruction and the sham-obstructed gut. The inflammation was significantly more pronounced in the serosa and external muscle layer than in the mucosa-submucosa. Acid-base balance in obstructed animals showed a significant metabolic alkalosis, whereas serum albumin and electrolytes were normal. Lumen fluid in obstructed animals showed low levels of albumin and total calcium as compared with serum, whereas fluid from the peritoneal cavity of obstructed rats showed high contents of albumin. Indomethacin and hydrocortisone given intravenously to obstructed animals significantly reduced the degree of extravasated Eb-albumin in the obstructed gut wall. Sham-operated animals showed net fluid absorption, whereas obstructed rats showed net fluid secretion. Secretion in obstructed animals was in all cases reversed into net fluid absorption after intravenous administration of indomethacin and hydrocortisone. These findings suggest that a pronounced inflammation occurs in the wall of the obstructed small intestine and that this inflammation plays an important role in the pathogenesis of the profuse fluid losses of obstructive ileus.

We have previously presented evidence for a non-adrenergic, vagally mediated colono-gastric inhibitory reflex induced by distension of the colon. We also found that pain stimulation by putting pressure on a testicle induced a pronounced gastric relaxation mediated by both adrenergic and vagal non-adrenergic fibres in anesthetized rats. Previous in vitro studies by other workers have strongly indicated that vasoactive intestinal polypeptide (VIP) is a neural mediator of gastric relaxation. The aim of the present in vivo study was to investigate, in anesthetized rats, whether VIP is involved in the gastric reflex relaxation induced by colonic distension and pain stimulation. A volumetric method was used to monitor changes in gastric volume. Gastric reflex relaxation following colonic distension was significantly and markedly inhibited by VIP antiserum as compared to the control relaxation before administration of the antiserum. Non-immunized control serum did not significantly influence gastric relaxation caused by colonic distension. Pain-induced gastric relaxation was moderately but significantly reduced after the administration of VIP antiserum but not after control serum. The selective beta 2-adrenoceptor agonist, salbutamol, induced a pronounced gastric relaxation of the same magnitude before and after the administration of VIP antiserum. VIP antiserum changed the pattern of gastric motility by inducing a specific type of gastric contraction appearing spontaneously or in response to colonic distension. A close intra-arterial injection of VIP induced gastric relaxation and inhibition of phasic gastric contractions. The present results in the rat suggest that VIP or a VIP-like peptide is involved in gastric reflex relaxation induced by colonic distension and pain stimulation.

Painful stimuli have been shown to inhibit gastric motility in animal experiments and delay gastric emptying in humans. The aim of the present study was to investigate in detail mechanisms involved in pain-induced gastric inhibition. Pain stimulation by exerting pressure on a testicle induced a prompt gastric relaxation which lasted throughout the period of stimulation. Pain-induced gastric relaxation was significantly reduced by the selective alpha-1 blocker, prazosin, and by the non-selective beta-blocker, propranolol. Similarly pain-induced inhibition of gastric tone was significantly reduced by bilateral cervical vagotomy. In contrast, gastric relaxation following pain stimulation was significantly potentiated by the selective adrenergic alpha-2 blocker, yohimbine. Combined administration of prazosin and propranolol followed by bilateral cervical vagotomy abolished gastric relaxation in response to pain stimulation. In conclusion, gastric relaxation in response to painful stimulation was found to be reflex-mediated via sympathetic neurons acting on alpha-1 and beta receptors and possibly also via vagal non-adrenergic fibres. Pain-induced inhibition of gastric tone was significantly increased by yohimbine. It is suggested that yohimbine by blocking presynaptic inhibitory receptors on adrenergic neurons facilitates the release of noradrenaline in response to pain stimulation.

The aim of the present in vivo study was to investigate in anaesthetized rats, the effects of selective adrenergic agonists and antagonists on basal gastric tone and phasic contractions by the use of a volumetric method. L-phenylephrine, an alpha-1 agonist, induced hypertension, bradycardia and a significant gastric relaxation. Clonidine, an alpha-2 agonist, caused hypotension, bradycardia and a significant gastric contraction and a reduction of the amplitude of phasic contractions. Salbutamol, a beta-2 agonist, induced a dose-dependent tachycardia and a significant inhibition of gastric tone whereas prenalterol, a beta-1 agonist, induced tachycardia without any significant influence on gastric basal tone. Yohimbine, an alpha-2 blocker, significantly decreased gastric basal tone and reversed the inhibition of phasic contractions induced by clonidine. Prazocine, a selective alpha-1 blocker, and propranolol, a non-selective beta-blocker, had no significant influence on gastric basal tone or phasic contractions. It is concluded that sympathetic inhibition of basal gastric tone in the rat is mediated by alpha-1 and beta-2 adrenergic receptors. Activation of alpha-2 adrenergic receptors significantly increased basal gastric tone and reduced the amplitude of phasic contractions. A blockade of alpha-2 receptors significantly decreased basal gastric tone and restored the amplitude of phasic contractions.

Burn injury was induced in anesthetized rats by exposing the abdominal skin to a temperature of 55 degrees C by means of a hot aluminum rod. Temperature was registered on a Grass polygraph. Skin exposure was interrupted when hot rod temperature had decreased to 45 degrees C. A full-thickness burn trauma of the skin was induced as judged from histologic sections. The burned skin was dissected and extravasation of Evans blue (EB) bound plasma albumin was quantified by a spectrophotometric technique and visualized by fluorescence microscopy. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA) for 1.5 h starting 15 min after inducing the burn injury. In one control group (n = 14) the thermal injury was treated with placebo cream. A second control group (n = 15) was topically treated with placebo cream without being exposed to thermal trauma. Results showed a significant inhibition of EB-albumin extravasation in the skin of burned rats treated with lidocaine-prilocaine cream compared with placebo-treated burned skin (P less than 0.001). EB-albumin contents in the skin of burned rats treated with lidocaine-prilocaine cream did not differ significantly from unburned skin (P greater than 0.05). In the second set of experiments continuous iv lidocaine infusions at a rate of 5 (n = 10), 10 (n = 12), 20 (n = 10), or 30 (n = 10) micrograms.kg-1.min-1 was given.(ABSTRACT TRUNCATED AT 250 WORDS)