When characterizing small intestine early lesions in studies concerning intestinal hypoperfusion in pigs, authors faced a significant difficulty when trying to standard the oedema grading to allow an accurate comparison between groups. Therefore, specific alterations were assumed to characterize grade1 (G1), grade2 (G2) and grade3 (G3) oedema.
Material and Methods
Eighteen Large White pigs underwent total intravenous anaesthesia (TIVA) with propofol and remifentanil. 25 ml/kg of arterial blood were removed from the femoral artery over 20 minutes. Volume was replaced using Ringer Lactate in Gr1 (n=6) and Hydroxyethyl starch 130/0.4 in Gr2 (n=6), 20 minutes after bleeding. Animals of G3 (n=6) were under TIVA without any haemorrhage and volume replacement. One hour after, pigs were euthanized and small intestine samples taken for histopathological examination. Oedema was described and classified in a specific scale:
G0-Normal–normal central lacteal
G2-Moderate-lacteal dilation and/or oedema of lamina propria
G3-Marked–lacteal dilation dilation, oedema of lamina propria, and/or presence of submucosal oedema
Pictures were made to better characterize the scale used.
G2 oedema was predominant in duodenum in Gr1 (n=3)...
The potential participation of PAF-acether (PAF) on the paw oedema triggered by enterolobin was investigated. Intraplantar injections of enterolobin )5-20 µg/paw) yielded a dose response curve for edema which appeared after 30 min, peaked in the interval between 2-4 h and faded after 24h. The pre-treatment with BN 52021, but not with other PAF antagonists such as PCA 4248 or WEB 2086, significantly blocked enterolobin-induced oedema. To clarify better the discrepant results obtained with the PAF antagonists, desensitization to PAF was performed. The oedema triggered by enterolobin was not modified in paf desensitized animals. It was concluded that the paw inflammation induced by enterolobin does not require PAF mechanism.
Regional cerebral blood flow (rCBF) and oedema following profound temporary ischaemia were studied in the gerbil. Ninety-four per cent of animals died within 24 hours of reperfusion; 50% by 4 hours. Regional differences in oedema (specific gravity method), Evans blue (EB) staining and rCBF (hydrogen clearance technique) occurred. Oedema developed during arterial occlusion, being inversely proportional to residual flow and was markedly exacerbated during reperfusion. Reperfusion hyperaemia was maximal in the parietal and hippocampal regions (ischaemic rCBF 4 ml 100 g-1 min-1). Oedema was disappearing in all areas by 3 hours of reperfusion and autoregulation returned in the occipital region (mean ischaemia rCBF 8 ml 100 g-1 min-1). EB staining and haemorrhage appeared in the thalamus (rCBF 10 ml 100 g-1 min-1) as oedema was decreasing. It is suggested that the amount of oedema and hyperaemia during reperfusion are dependent on the severity of the ischaemia. Areas of moderate ischaemia (8-10 ml 100 g-1 min-1) show little hyperaemia and greater oedema resolution during reperfusion as compared to areas of severe ischaemia (circa 4 ml 100 g-1 min-1) where there is marked hyperaemia with less oedema resolution. Early in the reperfusion period...
1. Oedema formation induced by intradermal capsaicin has been studied in rabbit skin. The effect of the anti-inflammatory steroid dexamethasone and also of a range of known inhibitors of oedema formation have been investigated in order to elucidate mechanisms involved in capsaicin-induced oedema formation. 2. Oedema formation, in response to intradermally-injected test agents, was measured by the local extravascular accumulation of intravenously injected 125I-labelled albumin. In separate experiments skin blood flow was assessed by the clearance of intradermally-injected 133xenon. 3. Oedema formation induced by intradermal histamine (3 nmol) and bradykinin (1 nmol), when in the presence of vasodilator doses of calcitonin gene-related peptide (CGRP) (3 pmol) or prostaglandin E1, (PGE1) (10 pmol), was significantly inhibited (P < 0.01) in rabbits pretreated with intravenous dexamethasone (3 mg kg-1, -4 h). In contrast dexamethasone had no effect on capsaicin (3 mumol)-induced oedema formation or, on capsaicin (30-100 nmol)-induced blood flow. 4. Oedema formation observed in response to intradermal capsaicin (3 mumol) was significantly inhibited (P < 0.01) when the selective capsaicin antagonist, ruthenium red (3 nmol) was co-injected. This suggests that the mechanism of capsaicin-induced oedema involves activation of sensory nerves. However...
The present study was designed to investigate the influence of long-term systemic treatment with Mycobacterium bovis bacillus Calmette-Guérin (BCG, 1 dose per animal, containing 6×104 colony-forming-units (CFu), 5 to 75 days beforehand) on oedema formation induced by intradermal injection of B1 and B2 selective agonists. The interaction between the B1 agonist des-Arg9-bradykinin and bradykinin was also investigated.Intradermal injection (i.d.) of the B2 selective agonist tyrosine8-bradykinin (1–10 nmol) in naive (saline pretreated) animals, or in animals that had received BCG (30 days beforehand), caused dose-related and very similar oedema formation (ED50; 1.1 and 1.0 nmol/paw, respectively). I.d. injection of the selective B1 agonists des-Arg9-bradykinin (100 nmol) or des-Arg10-kallidin in naive animals caused very little paw oedema (0.04±0.06 and 0.07±0.02 ml, respectively, n=5). However, i.d. injection of des-Arg9-bradykinin (10–300 nmol) or des-Arg10-kallidin (3–100 nmol) in animals pretreated with BCG, 30 days previously, resulted in dose-related and marked oedema formation, with mean ED50 values of 20.1 and 5.5 nmol/paw, respectively.Oedema caused by i.d. injection of des-Arg9-bradykinin (100 nmol/paw) in rats pretreated with BCG was evident 5 days after treatment...
The contribution of calcitonin gene-related peptide (CGRP) to bilateral oedema formation in the rat hindpaw following an unilateral challenge with CGRP was investigated.Rats were injected into the left hindpaw with either saline, CGRP or a CGRP antagonist (CGRP8–37). All injections were given in a double blind fashion and in a volume of 100 μl. CGRP and CGRP8–37 were administered in concentrations of 75, 150 or 300 pmol. Volumes of the right and left hindpaw were measured every hour for 5 h by plethysmometry.Injection of CGRP 300 pmol into the left hindpaw resulted in a bilaterally increased hindpaw volume after 5 h as compared with the groups given saline. No changes were found in hindpaw volumes following the injection of either 75 or 150 pmol of CGRP or 75, 150 or 300 pmol of CGRP8–37 as compared with saline injection.To elucidate whether or not the bilateral oedema formation was related to a release of endogenous CGRP, microdialysis of the contralateral hindpaw was carried out, and concentrations of CGRP-like immunoreactivity (-LI) were determined by radioimmunoassay and high performance liquid chromatography. Injection of CGRP 300 pmol into the left hindpaw increased the release of CGRP-LI into the right hindpaw perfusate after 4 and 5 h. No changes in CGRP-LI were detected in the right hindpaw perfusate following challenge with saline or CGRP8–37.To study the contribution of the nervous system to the contralateral release of CGRP-LI...
BACKGROUND—Cerebral oedema is a
major cause of morbidity and mortality in children with insulin
dependent diabetes. AIMS—To determine the risk and
outcome of cerebral oedema complicating diabetic ketoacidosis (DKA). METHODS—All cases of cerebral
oedema in England, Scotland, and Wales were reported through the
British Paediatric Surveillance Unit between October 1995 and September
1998. All episodes of DKA were reported by 225 paediatricians
identified as involved in the care of children with diabetes through a
separate reporting system between March 1996 and February 1998. Further
information about presentation, management, and outcome was requested
about the cases of cerebral oedema. The risk of cerebral oedema was
investigated in relation to age, sex, seasonality, and whether diabetes
was newly or previously diagnosed. RESULTS—A total of 34 cases of
cerebral oedema and 2940 episodes of DKA were identified. The
calculated risk of developing cerebral oedema was 6.8 per 1000 episodes
of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to
established (3.8 per 1000) diabetes. There was no sex or age
difference. Cerebral oedema was associated with a significant mortality
(24%) and morbidity (35% of survivors). CONCLUSIONS—This first large
population based study of cerebral oedema complicating DKA has produced
risk estimates which are more reliable and less susceptible to bias
than those from previous studies. Our study indicates that cerebral
oedema remains an important complication of DKA during childhood and is
associated with significant morbidity and mortality. Little is known of
the aetiology of cerebral oedema in this condition and we are currently
undertaking a case control study to address this issue.
1. The effect of calcitonin gene-related peptide (CGRP) when given with or as a pretreatment to oedema inducing agents was investigated in the skin and paws of male Wistar and Sprague Dawley rats. 2. Oedema formation at intradermally-injected sites in the skin was measured by a 125I-labelled human serum albumin accumulation technique and paw oedema was measured by a weight displacement technique. 3. CGRP (30 pmol) when given with, or as a 20 min pretreatment, markedly potentiated oedema formation induced by substance P (100 pmol) in rat skin. In comparison, CGRP had little effect on 5-hydroxytryptamine (5-HT, 0.1-3 nmol)-induced oedema when given as a co-injection but significantly potentiated 5-HT-induced oedema when given as a 20 min pretreatment in the skin. Similar results were obtained in both Wistar and Sprague Dawley rats. 4. Pretreatment with CGRP (30 pmol) had little modulatory effect on oedema induced by substance P (100 pmol) in the presence of the vasodilator prostanoid, prostaglandin E1 (PGE1, 850 pmol) in the skin of Wistar rats. 5. Pretreatment with CGRP (30 pmol) caused a non-significant increase in carrageenin (300 micrograms)-induced oedema in the hind paw of Wistar rats. Capsaicin (100 nmol) given as a pretreatment had little effect on carrageenin-induced oedema. 6. CGRP (30 pmol)...
1. The effect of pretreatment with bacterial endotoxin (LPS, 10 micrograms, i.v., 24 h) on the bradykinin B1 and B2 receptor-induced oedema in the rat paw, and the interaction of B1-mediated responses with other inflammatory mediators, was investigated. 2. Intraplantar (i.pl.) injection of the selective B1 agonist, des-Arg9-BK (DABK, 100 nmol) in naive animals pretreated with the angiotensin converting enzyme inhibitor, captopril caused a small increase in paw volume (0.04 +/- 0.003 ml, mean +/- s.e. mean, n = 6), while the B2-selective agonist, tyrosine8-bradykinin (T-BK, 3 nmol) induced marked oedema (0.36 +/- 0.02 ml). However, i.pl. injection of DABK (3-300 nmol) in rats pretreated with LPS (24 h beforehand) resulted in a marked dose- and time-related increase in paw volume, with mean ED50 of 24.1 nmol. In contrast, oedema caused by T-BK (3 nmol) was reduced by 79 +/- 4% in animals treated with LPS when compared with naive animals. 3. Oedema caused by prostaglandin E2 (PGE2, 10 nmol) was unaffected by LPS treatment, while oedema induced by histamine (100 nmol), 5-hydroxytryptamine (5-HT, 10 nmol) and substance P (SP, 3 nmol) was reduced (P < 0.05). 4. The selective B1 antagonist, des-Arg9[Leu8]-BK (100-300 nmol), produced dose-dependent inhibition of DABK (100 nmol)-induced paw oedema in LPS-treated animals with mean IC50 of 134 nmol...
1. The possibility that tachykinin NK1 receptors are involved in the plasma extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer venom (PNV) in rat dorsal skin in vivo has been investigated. 2. Local oedema formation induced by the i.d. injection of test agents was measured by the extravascular accumulation of intravenously (i.v.) injected 125I-labelled human serum albumin over a 30 min period. 3. The tachykinin NK1 agonist, GR73632 (30 pmol per site), induced local oedema formation which was potentiated by co-injection with the neuropeptide vasodilator, calcitonin gene-related peptide (CGRP, 10 pmol per site). The non-peptide tachykinin NK1 receptor antagonist, SR140333 (0.03-1 nmol per site co-injected, i.d.) significantly inhibited (0.3 nmol per site, P < 0.05; 1 nmol per site, P < 0.001) local oedema formation induced by GR73632 with CGRP but not that induced by histamine (10 nmol per site) with CGRP. 4. PNV (0.03-0.3 microgram per site) injected i.d. induced dose-dependent local oedema formation. SR140333 (1 nmol per site, co-injected i.d.) inhibited oedema formation; with complete inhibition observed at doses of 0.03 microgram (P < 0.05) and 0.1 microgram (P < 0.001); and partial inhibition (50%) observed with the highest dose of PNV...
Light microscopic morphometry was utilized to examine the distribution of fluid in the interstitium around arteries, veins and within bronchovascular bundles in hydrostatic oedema, comparing it with previous control and permeability oedema experiments. Pulmonary artery wedge pressure was raised with fluid overload and an aortic balloon in five anaesthetized dogs to produce oedema (wet weight to dry weight ratios of 11.66 +/- 0.84). Lung lobes were fixed by freeze-substitution at 20 mmHg airway pressure. Photomicrographs of arteries, veins and bronchovascular bundles were taken, and areas were digitized to obtain the following: for arteries and veins, an oedema ratio=perivascular oedema cuff area/vessel area; for bronchovascular bundles, T=total bundle area, A1=interstitial area around airways, B=airway (respiratory bronchiole, bronchiole, or bronchus) area, A2=periarterial interstitium, V=artery area. From these, oedema ratios were calculated as A1/B and A2/V. We found that the oedema ratios were greater (P less than 0.01) for arteries (1.18, n=675) than veins (0.56, n=263), and were greater for the larger vessels; A1 rose significantly (P less than 0.01) only in bronchovascular bundles with bronchioles and bronchi, not in those with respiratory bronchioles; A2 increased from three- to 25-fold (P less than 0.01) in all bundles; A1/B only increased in bundles with bronchi while A2/V increased two- to six-fold in all bundles with oedema compared with controls. We conclude that these preferential patterns of distribution resemble those reported in permeability oedema...
1. We have investigated the mechanism of capsaicin-induced mouse ear oedema compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the possible involvement of neuropeptides in the development of capsaicin-induced oedema. 2. Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of mice produced immediate vasodilatation and erythema followed by the development of oedema which was maximal at 30 min after the treatment. This oedema was of shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3. Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate metabolites including platelet activating factor (PAF) were administered before capsaicin (250 micrograms per ear) application, while these agents significantly prevented AA-induced oedema. Dexamethasone, histamine H1 and/or 5-hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were effective in inhibiting both models. Furthermore, a Ca(2+)-channel blocker and the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin oedema but had no effect on AA-induced oedema. 4. Phosphoramidon (50 micrograms kg-1, i.v.), an endopeptidase inhibitor, markedly (P < 0.001) enhanced only capsaicin-induced ear oedema...
Macular oedema typically results from blood–retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss. We unexpectedly observed microcystic macular oedema using spectral domain optical coherence tomography in patients with multiple sclerosis who did not have another reason for macular oedema. We therefore evaluated spectral domain optical coherence tomography images in consecutive patients with multiple sclerosis for microcystic macular oedema and examined correlations between macular oedema and visual and ambulatory disability in a cross-sectional analysis. Participants were excluded if there was a comorbidity that could account for the presence of macular oedema, such as uveitis, diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) patients with multiple sclerosis. No macular oedema was identified in 52 healthy controls assessed over the same period. The microcystic oedema predominantly involved the inner nuclear layer of the retina and tended to occur in small...
BACKGROUND: Pulmonary oedema may complicate the perioperative period and the aetiology may be different from non-operative patients. Diagnosis may be difficult during anaesthesia and consequently management may be delayed. OBJECTIVES: To examine the role of a previously described core algorithm "COVER ABCD–A SWIFT CHECK", supplemented by a specific sub-algorithm for pulmonary oedema, in its management occurring in association with anaesthesia. METHODS: The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. RESULTS: Pulmonary oedema was identified in 35 (<1%) of the first 4000 reports to AIMS. The most frequent presenting sign was hypoxia (46%) and the most specific sign was the presence of frothy sputum (23%). The core algorithm, although successful in the management of the initial physiological upset, was found to be inadequate for the ongoing management of pulmonary oedema. A specific sub-algorithm for the management of perioperative pulmonary oedema was devised, tested against the reports and would have been effective, if properly applied...
Objective: To examine the effect of topically applied tea tree oil (TTO) on histamine-induced oedema in the ears of mice.Methods and results: For BALB/c mice, 10 7 undiluted TTO applied immediately after, but not 30 min before intradermal injection of 600 7g histamine in 10 7l, significantly suppressed oedema development. TTO applied after histamine injection also suppressed histamine-induced oedema in C57/BL6 mice. TTO applied immediately after intradermal injection of compound 48/80 (200 7g in 10 7l saline) also significantly reduced ear swelling. TTO suppressed histamine-induced oedema to the same extent in capsaicin-treated (neuropeptide-depleted) and control mice which suggests that TTO does not inhibit histamine-induced oedema by regulating the activity of peripheral sensory neurons. Terpinen-4-ol, the major water-soluble component of TTO, was equivalent in potency to TTO in the suppression of histamine-induced ear swelling.Conclusion: Topical application of TTO, and in particular terpinen-4-ol, may be effective in controlling histamine-induced oedema often associated with Type I allergic immediate hypersensitivities.; C. Brand, S.L. Townley, J.J. Finlay-Jones and P.H. Hart; The original publication can be found at www.springerlink.com
Elevated levels of substance P (SP) have previously been found following ischaemic stroke and traumatic brain injury. Inhibiting the main SP receptor (neurokinin-1 (NK1)) reduces oedema and improves functional outcome in both settings. As this thesis details, we hypothesised that SP plays a similarly deleterious role following intracerebral haemorrhage (ICH).
We further hypothesised that the post-ICH effects of intracerebral thrombin (which is known to play a major role in post-ICH secondary injury) are at least partly SP-mediated. Thrombin, similarly to SP, is known to play a deleterious role following both ischaemic stroke and traumatic brain injury. Previous research has also demonstrated that thrombin causes cutaneous oedema by an SP-dependent mechanism.
Three hundred and forty three male Sprague-Dawley rats were used, and variously subjected to collagenase ICH, autologous ICH, intracerebral thrombin injection and intracerebral injection of SP. The sequelae of these various injuries was assessed, as well as the effect of antagonists to the main substance P receptor (NK1R), using functional testing, histological analysis, ELISA, real-time RT-PCR, wet-weight dry weight (for assessment of oedema) and Evans blue (for assessment of blood-brain barrier integrity). The effect of prior splenectomy on oedema following ICH was also assessed.
Elevated levels of SP were demonstrated post-ICH in the two different ICH models...
Raised intracranial pressure (ICP) following SAH predicts poor outcome and is due to hemorrhage volume and possibly brain oedema, hydrocephalus and increased volume of circulating intracranial blood. Interventions that reduce oedema may therefore reduce ICP and improve outcome. The neuropeptide substance P (SP) mediates vasogenic oedema formation in animal models of ischemic stroke, intracerebral hemorrhage and brain
trauma, and may contribute to the development of increased ICP. Blockade of the SP NK1 tachykinin receptor using n-acetyl-l-tryptophan (NAT) reduces brain oedema and improves outcome in these models. This intervention had not previously been tested in models of SAH. This study therefore assessed whether SP mediates oedema formation in experimental SAH, and whether NAT treatment impacted on ICP and functional outcome.
SAH was induced in adult male Sprague-Dawley rats by either injection of autologous blood into the prechiasmatic cistern (injection SAH) or by endovascular arterial puncture of the Circle of Willis (filament SAH). NAT was injected (i.v.) at 30 minutes after induction of SAH. Subgroups were assessed for brain water content, immunoreactivity to SP, albumin immunoreactivity and functional outcome at 5...
[Conclusion] In the present thesis, I have shown that single administration of an AQP4 & 1 antagonist at 5
h, an AQP4 agonist at 48 h and the sequential treatment with both of the compounds at their
optimal time points is beneficial to physiological and functional outcome following diffuse
TBI. At a physiological level there was an attenuation of post traumatic cerebral oedema and
of brain albumin content, with these beneficial effects occurring in the absence of any
changes in water channel expression. Functionally, each compound improved functional
motor outcome after TBI when they were administered at their optimal time point. Sequential
treatment with both compounds proved even more efficacious than single interventions. The
sequential treatment with the antagonist and then the agonist augmented what seemed to be a
protective response of the brain against posttraumatic oedema, namely an initial
downregulation of AQP channels followed by a later upregulation. This alteration in
expression was mimicked by initial inhibition with the antagonist followed by facilitation of
water transport during the resolution phase of oedema. Taken together these results provide
evidence in favour of a pharmaceutical treatment for the attenuation of injury-induced brain
OBJECTIVE—To demonstrate postinfarction myocardial oedema in humans with particular reference to the longitudinal course, using magnetic resonance imaging (MRI). DESIGN—Prospective observational study. Subjects were studied one week, one month, three months, six months, and one year after presenting with a myocardial infarct. SETTING—Cardiology and magnetic resonance departments in a Danish university hospital. PATIENTS—10 patients (three women, seven men), mean (SEM) age 58.2 (3.20) years, with a first transmural myocardial infarct. MAIN OUTCOME MEASURES—Location and duration of postinfarction myocardial oedema. RESULTS—All patients had signs of postinfarction myocardial oedema. The magnetic resonance images were evaluated by two blinded procedures, employing two MRI and two ECG observers: (1) MRI determined oedema location was compared with the ECG determined site of infarction and almost complete agreement was found; (2) the time course of postinfarction myocardial oedema was explored semiquantitatively, using an image ranking procedure. Myocardial oedema was greatest at the initial examination one week after the infarction, with a gradual decline during the following months (Spearman's rank correlation analysis: ρobserver 1 = 0.94 (p < 0.0001) and ρobserver 2 = 0.97 (p < 0.0001)). The median duration of oedema was six months. CONCLUSIONS—Postinfarction myocardial oedema seems surprisingly long lasting. This observation is of potential clinical interest because the oedema may have prognostic significance. Keywords: myocardial infarction; myocardial oedema; magnetic resonance imaging
A 57-year old female civilian was suffocated by an intruder. The victim (experienced severe dyspnoea) but violently resisted the assault. Two hours after this event, on admission to a Trauma Centre, she demonstrated left facial swelling with low percutaneous oxygen saturation. Chest X-ray and computed tomography demonstrated pulmonary oedema. This improved dramatically within a short time and she was discharged on the 5th hospital day. Pulmonary oedema induced by suffocation has been reported only rarely. The possible mechan-isms by which pulmonary oedema might form after the relief of airway obstruction are discussed.