Significant Extravasation Research Articles

Changes in cerebral blood flow and blood brain barrier in the gerbil hippocampal CA1 region following repeated brief cerebral ischemia.

Neuronal damage and changes in cerebral blood flow (CBF) and the permeability of the blood-brain barrier (BBB) following repeated brief periods of ischemia were studied in Mongolian gerbils. The cerebral ischemia was produced by three repeated occlusions of bilateral common carotid arteries for 3 min at 1-h intervals. CBF and permeability of the BBB were examined with tracers (China ink and silver nitrate) at 1, 3, and 7 days post ischemia using light and electron microscopy. Three days after the reperfusion, significant extravasation of tracers, consequential reduction of CBF, extensive neuronal destruction, and intravascular platelet aggregation were observed. Such vascular changes in the CA1 region were more severe than those in the frontal cortex. These findings strongly support the view that microcirculatory disturbance may be a mechanism responsible for delayed neuronal death in the CA1 region of the hippocampus.

Early and late treatment of iatrogenic injection damage

Extravasation injuries can result in extensive soft-tissue defects. On the cellular level there are five different pathophysiological mechanisms. Early treatment (surgical removal of the extravasated material within 24 h) and late treatment (debridement and coverage) are different. Thirty-two patients who suffered a significant extravasation were treated surgically by the Department of Plastic Surgery between 1989 and 1997. In 8 patients, referred within the first 24 h, the extravasated material could be removed by saline flushout. None of these patients developed soft-tissue defects or skin necrosis. The other 24 patients were referred late (mean 19 days after the injury). Patients with defects of the dorsum of the hand or cubital fossa area who underwent debridement, temporary wound coverage and skin grafting (n = 11) presented complete healing 52 days after the referral. Defects of the same regions covered by a flap after debridement (n = 6) healed within 14 days. The healing time of defects of the forearm (n = 2) and dorsum of the foot (n = 5) was a mean of 15 days after skin grafting. Cytotoxic and osmotically active substances should be removed by saline flushout within 24 h. In defects of the dorsum of the hand and cubital fossa, early debridement and coverage with an adequate flap should be performed.

Ethanol-mediated neutrophil extravasation in feline pancreas.

Ethanol is a common cause of both acute and chronic pancreatitis. Studies in other organs suggest that polymorphonuclear neutrophils activated by ethanol may cause tissue injury in a variety of conditions. The aim of this study was to investigate the effects of ethanol on neutrophil extravasation in the feline pancreas. Pancreata were isolated and perfused at different flow rates with varying concentrations of ethanol in either a physiological or neutrophil depleted perfusate. Neutrophil extravasation was assessed by measuring pancreatic tissue myeloperoxidase (MPO) activity. Ethanol at 2.5% (54.25 mmol/liter) was the lowest concentration that still caused significant neutrophil extravasation (3.1+/-0.8 vs 1.9+/-0.2 units, P<0.05) and was accompanied by an increase in vascular resistance of 15%. Reduction of pancreatic perfusion by 15% did not significantly increase neutrophil extravasation. (1.1+/-0.3 vs 1.6+/-0.2 units, NS) Perfusion of the pancreas with neutrophil-depleted blood containing either ethanol or saline, followed by perfusion with an ethanol-free perfusate, showed an increase in neutrophil extravasation in the ethanol group compared to the control group (3.2+/-0.9 vs 1.9+/-0.2 units, P<0.05). In conclusion, ethanol causes neutrophil extravasation in the feline pancreas independent of blood flow changes and occurs despite the absence of direct neutrophil exposure to ethanol.

Transcatheter embolization of post-traumatic gluteal haemorrhage: Case report

SummaryTranscatheter embolization has proved to be an effective treatment for patients presenting with pelvic haemorrhage. Superselective catheterization with microcatheters facilitates the approach to the bleeding vessel and enables safer and more effective embolization. A 45-year-old man was admitted to hospital after blunt trauma to the left gluteal region. He complained of a painful enlarging mass in the left gluteal region. Radiography of the pelvis revealed absence of fracture. Selective angiography displayed significant extravasation from the left superior gluteal artery. Embolization was performed. The patient was discharged 2 days after admission with a resolving left gluteal haematoma.

Cystography after radical retropubic prostatectomy: clinical implications of abnormal findings.

In many institutions, cystography is obtained routinely after radical retropubic prostatectomy to assess the integrity of the vesicourethral anastomosis before the removal of the catheter. This study presents the Indiana experience with cystograms performed following radical retropubic prostatectomy. The experience with 260 cystograms performed in 245 consecutive patients following radical retropubic prostatectomy was reviewed retrospectively, with a special reference to the clinical implications of abnormal findings. After a standard catheterization period of 14 to 21 days (mean, 19.2), 94.3% of the catheters were removed safely without adverse clinical consequences. The presence of a minimal contained contrast extravasation did not affect outcome after the removal of the catheter. The overall incidence of clinically significant extravasation was found to be 5.7% and was further reduced to 2.4% if extravasation was not suggested clinically in the postoperative course. Based on the current literature, significant extravasation is a common finding during the first 5 to 8 postoperative days. Therefore, management strategies advocating early urethral catheter removal should include routine cystographic studies. Otherwise, cystographic confirmation of anastomotic integrity before the removal of the catheter following 14 to 21 days of catheterization is not indicated in the routine postradical prostatectomy patient.

Opening of the blood-brain barrier during cortical superfusion with histamine

Histamine may influence cerebral microcirculation from the intravascular and parenchymal side. The latter route can be simulated by cortical superfusion. The effect of cortical superfusion with histamine (10 −9−10 −3 M) on blood-brain barrier (BBB) permeability was studied in the cat by measuring extravasation of the tracers Na +-fluorescein (MW 376) or fluorescein isothiocyanate (FITC) labelled dextran (MW 62,000 or 145,000) by intravital fluorescence microscopy. Histamine induced an opening of BBB resulting in extravasation of small and large molecular weight tracers with threshold concentrations of 10 −9, 10 −8 and 10 −6 M for Na +-fluorescein, FITC-dextran 62,000 and 145,000, respectively. Once tracer extravasation had started the degree of extravasation increased with increasing concentrations of histamine in the superfusion fluid. Similar to histamine the H 2 agonist impromidine (3 × 10 −12−3 × 10 −9 M) induced a concentration dependent extravasation of Na +-fluorescein. 2-Pyridylethylamine which is 3–4 times more selective for H 1 than for H 2 receptors also induced an extravasation of Na +-fluorescein. Cortical superfusion with mepyramine (10 −7 M) or cimetidine (10 −4 M), which block the H 1 and H 2 receptors, respectively, already induced significant extravasation of Na +-fluorescein by themselves. These compounds could thus not be used as competitive antagonists to block histamine-induced extravasation. However, our data are in accord with data obtained during intravascular and topical application of histamine and support the hypothesis that H 2 receptors at the luminal and abluminal membrane of the endothelium mediate the opening of the BBB. In addition, histamine induced an increase of pial venular and arteriolar diameter in concentrations above 10 −8 and 10 −6 M, respectively. This may increase the driving force for extravasation. Thus, the role of histamine as a mediator of vasogenic brain edema is considered.

Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig

Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A 2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D 4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 ± 3 g: 2 weeks) and adult guinea pigs (512 ± 5 g: 11 weeks). In the same animals, we measured both lung resistance ( R L) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in R L in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in R L did not change with age (leukotriene D 4 > U-46619 > acetylcholine). In immature animals, the peak R L after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D 4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D 4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D 4 > U-46619). The amount of extravasation of Evans Blue dye after U-46619 (6 and 20 nmol/kg) and leukotriene D 4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels. We conclude that U-46619 and leukotriene D 4 administered intravenously caused a smaller degree of airway plasma exudation, but induced a greater airflow obstruction in the airways of immature guinea pigs, compared to airways of adult animals.

Airway allergy to trimellitic anhydride in guinea pigs: Different time courses of IgG 1 titer and airway responses to allergen challenge

Background: Trimellitic anhydride (TMA) is a low molecular weight chemical that may cause occupational asthma in human beings. The objectives of this study were to determine the time course of immune and airway responses to TMA in guinea pigs and to relate the immunologic response to the immediate responses in lung resistance (R L) and plasma exudation induced by allergen challenge. Methods: We studied the effects of time course after sensitization on airway response to TMA in guinea pigs actively sensitized to free TMA, given by intradermal injection (0.1 ml of 0.3% TMA in com oil). During weeks 1, 2, 3, 5, and 8 after sensitization, anesthetized animals were challenged with TMA conjugated to guinea pig serum albumin (TMA-GPSA), instilled via the airway route. Nonsensitized animals were challenged with the same amount of conjugate 4 weeks after intradermal injection of corn oil only. In the same animal, we measured both R L to monitor airflow obstruction and extravasation of Evans blue dye (20 mg/kg) to quantify airway plasma exudation. Results: Instillation of TMA-GPSA (0.5%; 50 μl) into the tracheal lumen caused a significant increase in R L, reaching a maximum at 2.5 minutes after the instillation in the 1-week group (9.0 ± 5.9 cm H 2O/ml/sec) and between 5 and 6 minutes in the 2-, 3-, 5-, and 8-week groups (9.4 ± 4.8, 12.7 ± 5.5, 3.7 ± 1.1, and 1.7 ± 0.2 cm H 2O/ml/sec, respectively). The maximal increase in R L after the challenge in nonsensitized animals was 0.39 ± 0.05 cm H 2O/ml/sec. TMA-GPSA also produced significant extravasation of Evans blue dye at all airway levels in the senzitized groups, and the amount of dye in the peripheral airways was significantly greater than that in the trachea. Furthermore, the level of Evans blue dye in airway tissue increased with the time after sensitization, up to the latest time point tested (8 weeks). Specific IgG 1 antibodies to TMA-GPSA demonstrated by ELISA were detected in all animals in the 3-, 5-, and 8-week groups, with maximal levels 5 weeks after sensitization. Specific IgG 1 titers to TMA-GPSA significantly correlated with the level of Evans blue dye induced by challenge with TMA-GPSA but not with the increase in R L. Conclusions: Intradermal sensitization to free TMA induces specific airway allergy for a long period after sensitization. Specific IgG 1 antibodies to allergen may influence allergen-induced plasma exudation rather than the airflow obstruction in this animal model of TMA-induced asthma.

Comparison of serum phenobarbital levels after single versus multiple attempts at intraosseous infusion

Serum drug levels from a single intraosseous attempt in nontraumatized bone have proven comparable to levels from IV drug infusions. However, in the clinical situation, inexperienced personnel may make multiple intraosseous attempts, which could allow significant extravasation from multiple intramedullary entrance sites. Serum drug levels arising from multiple intraosseous attempts in traumatized bone were compared with those arising from single intraosseous attempts in nontraumatized bone. We administered phenobarbital to 24 dogs randomly divided into single- (11) and multiple-attempt (13) groups. In the multiple-attempt group, we created three intramedullary insertion sites in a linear fashion and infused through only the central site. In the single-attempt group, only a single infusion site was created. Phenobarbital then was infused into the intramedullary space, and central venous phenobarbital samples were collected at one-, three-, six-, and ten-minute intervals. The single-attempt group attained significantly higher serum phenobarbital levels at each interval compared with the multiple-attempt group (P less than .0001). Therefore, to be an effective mode of therapy, it is critical to achieve single-attempt intraosseous needle placement for intraosseous infusion.

Recombinant Neutral Endopeptidase Attenuates Substance P-Induced Plasma Extravasation in the Guinea Pig Skin

To determine whether exogenously administered neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) inhibits the substance P-induced increase in vascular permeability in the skin, we examined the effects of recombinant human NEP on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. Injection of substance P (2.5 X 10(-8) M) induced significant plasma extravasation in the skin (53 +/- 4 mm2 of Evans blue extravasation; mean +/- 1 SEM). In vitro incubation of substance P with recombinant human NEP prior to injection prevented the substance P-induced plasma extravasation in the skin in a dose-dependent fashion. Intradermal preinjection of recombinant human NEP partially inhibited plasma extravasation induced by subsequent injection of substance P (52 +/- 9% of the control without NEP). The H1 and H2 histamine antagonists pyrilamine and cimetidine, and a muscarinic antagonist, atropine, had no effects on substance P-induced responses. Two products of substance P degradation by NEP containing the carboxy-terminal portion, substance P7-11 and substance P8-11, were also without effect. These findings suggest that recombinant human NEP can attenuate substance P-induced increases in vascular permeability in guinea pig skin and, therefore, may be useful in treating dermatologic disorders in which abnormal responses to substance P or other neuropeptides cleaved by NEP may occur.

Pericatheter Retrograde Urethrography: Introduction of a New Device and Technique

We describe a new device and technique that allowed for radiographic evaluation of anastomoses before removal of the catheter in 80 patients who had undergone either radical retropubic prostatectomy or urethroplasty. Of these patients 11 showed significant extravasation and required continued catheterization. We advocate this procedure for documentation of complete urethral healing to prevent premature catheter removal.

Extravasation in the knee induced by antidromic stimulation of articular C fibre afferents of the anaesthetized cat.

Electrical stimulation of the cut distal end of the posterior articular nerve (p.a.n.) of the cat knee joint resulted in significant extravasation of plasma proteins and erythrocytes into the synovial cavity of the knee. This effect was mediated by group IV afferents (C fibres) since stimulation of p.a.n. suprathreshold for group II or III afferents but subthreshold for group IV afferents did not produce extravasation. Unmyelinated sympathetic efferent fibres in the joint nerve did not contribute to the extravasation and were responsible for a diminution of this response as shown by the enhanced extravasation occurring after adrenergic blockade. Plasma and erythrocyte extravasation was mediated by afferents containing substance P (SP), as demonstrated by the reversible abolition of extravasation when the substance P antagonist (D-Pro4,D-Trp7,9,10)-SP (4-11) was injected into the synovial cavity. In some animals it was observed that electrical stimulation of the cut distal end of p.a.n. in one limb resulted in extravasation in the contralateral knee joint. It is suggested that articular C fibre afferents could make a significant neurogenic contribution to the initiation or maintenance of inflammatory joint disease.

Leukotrienes C4, D4 and E4 cause widespread and extensive plasma extravasation in the guinea pig.

Intravenous injection of leukotriene C4 (1 nmol X kg-1) caused substantial plasma exudation in anesthetized guinea pigs, as evidenced by marked hemoconcentration 15% in 5 min) and significant extravasation of Evans blue. Fluorometric quantitation of Evans blue content in 38 selected tissues documented that leukotriene C4 caused significant plasma extravasation throughout the body, except for the brain, stomach, duodenum, colon and gonads. In particular, the respiratory and the uro-genital tracts, but also the conjunctiva, the esophagus, the bile ducts and the umbilical ligaments, were very sensitive to the edema-promoting effect of leukotriene C4. Intravenous injection of leukotriene D4 (1 nmol- X kg-1) or E4 (5 nmol X kg-1) evoked plasma extravasation with a distribution and magnitude that was similar to that induced by leukotriene C4. It is concluded that the three major constituents of slow reacting substance of anaphylaxis (SRS-A), leukotrienes C4, D4 and E4, cause a generalized and extensive plasma exudation that is consistent with the proposal that these leukotrienes are important mediators of inflammation.

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. B. Effect on the permeability to HRP

Alteration of blood-brain barrier (BBB) permeability by 2450 MHz CW microwaves was assessed semi-quantitatively after intravenous injection of horseradish peroxidase (HRP) and exposure of conscious, unrestrained rats to incident power densities of 0, 20 or 65 mW/cm 2 for 30, 90 or 180 min. Additional rats were exposed to ambient heat (42 ± 2 °C) for 30 or 90 min. None of the brain regions studied, with the exception of the normally leaky pineal gland showed extracellular HRP leakage attributable to microwave or thermally-induced breakdown of the blood-brain barrier. The mean ratio of HRP-labeled microvessel endothelium/total number of microvessels counted was determined for each brain region. Mean values for the cortex, hypothalamus, cerebellum and medulla of microwave-exposed and heated rats were consistently below those of corresponding sham levels. This decrease appeared to correlate inversely with power density and duration of exposure. Statistically significant deviation ( P <0.05) from sham mean values occurred in the cortex, hypothalamus, cerebellum and medulla of animals made hyperthermic with ambient heat or exposure to microwaves at 65 mW/cm 2 (specific absorption rate ≊ 13.0 W/kg) for 30 or 90 min. Additionally, electron microscopic evaluation of ultrathin sections taken from each of the 4 brain regions revealed no significant extravasation of HRP indicative of microwave or ambient heat-induced disruption of the bloo-brain barrier.

Substance P in sensory nerve fibres contributes to the development of oedema in the rat hind paw after thermal injury.

Immersion of the hind paws of anesthetized rats in hot water for 5 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45 degrees C, a maximal response was obtained between 55 degrees C and 60 degrees C. Pretreatment of rats 2 days after birth with 50 mg kg-1 capsaicin significantly reduced the Evans blue extravasation induced by hot water at 50 degrees C and 60 degrees C, whereas guanethidine pretreatment 24 h before the experiment caused a significantly increased response at 40 degrees C, 45 degrees C and 50 degrees C. When Evans blue was injected between 10 and 120 min after immersion of the paw in hot water, a significant extravasation of the dye was no longer detectable. However, the weight of the paw as well as the weight of the piece of skin taken for Evans blue quantification increased during this period indicating the progressive development of oedema in the skin and underlying tissues. In rats treated with capsaicin as neonates, the increase in paw weight after immersion in water of 50 degrees C for 5 min was significantly delayed during the first hour, but there was no difference after two hours. In rats pretreated with D-Arg1,D-Pro2-,D- Trp7 ,9, Leu11 -substance P, a substance P (SP) antagonist, the Evans blue extravasation was significantly reduced. However, the response, which remained in rats treated with capsaicin as neonates was not blocked by the SP-antagonist. 6 It is concluded that activation of peripheral branches of sensory SP neurones contributes to the initial massive protein extravasation and to the subsequent rate of development of oedema following heat injury. Release of histamine did not significantly contribute to this response at the lower temperatures, although the response was reduced by histamine receptor blocking drugs at 55 degrees and 60 degrees C. Decreasing the sympathetic vasoconstrictor tone by guanethidine resulted in an increased response.

Inhibition of cigarette smoke-induced oedema in the nasal mucosa by capsaicin pretreatment and a substance P antagonist.

The effect of cigarette smoke on vascular permeability in the rat nasal mucosa was studied using the Evans blue extravasation method. Exposure to smoke from cigarettes induced a significant extravasation of Evans blue in the nasal mucosa of normal rats, suggesting an increased vascular permeability to plasma proteins. The oedema response was correlated to tar, nicotine and vapour phase components in the smoke. The smoke-induced permeability effect was abolished in rats pretreated neonatally with capsaicin. Also, systemic or local pretreatment with [D-Arg, D-Pro, D-Trp, Leu]Substance P, a substance P antagonist, inhibited the permeability response to cigarette smoke. Insertion of a glass-fibre filter, which removes the particulate phase of the smoke (including nicotine), did not significantly reduce the permeability response. The present findings suggest that the smoke-induced oedema in the rat nasal mucosa is not caused by nicotine but by vapour-phase irritants, which activate capsaicin-sensitive C-fibre afferents. These neurons then release agents such as substance P or a related tachykinin which increase permeability to plasma proteins.

Angiographic Visualization for Percutaneous Renal Biopsy

Fifteen patients underwent visualization of the kidney for percutaneous biopsy by selective renal angiography. Biopsies were performed in 11 patients, and adequate renal tissue was obtained in all instances. Postbiopsy angiogram revealed pinpoint bleeding in ten patients and significant extravasation in one case, which was controlled with a selective epinephrine infusion. In four cases, biopsy was not performed when the cortex was found to be less than 5 mm thick.

Small coils for large hemorrhages

A 24-year-old man was stabbed in the left flank and right upper quadrant. Excretory urography revealed symmetric renal function bilaterally and a small left retropenitoneal mass. The hematocnit was 31 %. Because of the penetrating nature of the wound and relative hypotension, exploratory laparotomy was performed. At surgery, a very large left retropenitoneal hematoma extended from the splenic flexure to the pelvic inlet. Expansion of the hematoma was noted during penitoneal lavage and it was decided not to explore the retropenitoneum for fear of loss of tamponade and concomitant acute exsanguination. Postoperatively the hematocnit was 24% although blood pressure had stabilized with intraoperative crystalbid, colloid, and blood replacement. Abdominal aortography documented nightward aortic displacement and significant extravasation from a transected left third lumbar artery (fig. 1 A). Selective catheterization with a cobra catheter was followed by transcatheter Gelfoam embolization. During fluoroscopy it was obvious even the largest Gelfoam particles passed directly into the retropenitoneum due to high blood flow in the damaged vessel. A 5 French Gianturco catheter was then introduced into the third left lumbar artery and coil embolization was performed. Follow-up aortography revealed complete hemostasis (fig. 1 B). The patient made an uneventful recovery with no signs of infection, rebleed, or postembolization pain.

Extravasation of albumin in tissues of normal and septic baboons and sheep

Extravasation of albumin was measured in the tissues of normal and septic baboons and sheep. A group of normal animals (4 baboons, 4 sheep) was anesthetized for 6 hr and then given radioactively labeled albumin and red blood cells intravenously. The labeled albumin and red blood cells were allowed to equilibrate for exactly 15 min, at which time the animals were deliberately killed. Volumes of distribution of labeled albumin and red blood cells were then determined in the lungs, heart, liver, spleen, brain, and skeletal muscle of the baboons and in the lungs, heart, liver, and spleen of the sheep. Another group of animals (6 baboons, 14 sheep) were made septic by infusing live Escherichia coli organisms. The animals were resuscitated and volumes of distribution of albumin and red blood cells determined as in the normal animals. The volume of distribution of albumin was greater than the volume of distribution of red blood cells in all tissues in both species, both in control animals and in septic animals, with the exception of the spleen and skeletal muscle of the baboons and the spleen of the sheep. That is, albumin extravasated readily in most of the tissues of the animals, even within only 15 min of equilibration. There was moderate but significant extravasation in the lungs, heart, and brain. There was marked extravasation in the liver. Extravasation tended to be more pronounced in the septic animals. With this extensive degree of albumin extravasation, administration of albumin to patients, especially septic patients, is unlikely to prevent edema except in the spleen and skeletal muscle.

An extravascular component of contrast enhancement in cranial computed tomography. Part I. The tissue-blood ratio of contrast enhancement.

One can calculate the tissue-blood ratio of enhancement by analyzing the quantitative aspects of the CT scans of the cranium and blood samples both before and after the injection of contrast medium. This ratio is equivalent to that between the iodine content of a given volume of tissue and an equal volume of blood. Analysis of 47 normal patients, including 27 with pathological brain lesions, indicated that there is significant extravasation of contrast medium in patients with such lesions.