Search PubMed⌕ Search

Biomedical subjects

A Heimann

Publications and source records attributed to A Heimann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Investigation of iodine-123-labelled amino acid derivatives for imaging cerebral gliomas: uptake in human glioma cells and evaluation in stereotactically implanted C6 glioma rats.

In developing iodine-123-labelled amino acid derivatives for imaging cerebral gliomas by single-photon emission tomography (SPET), we compared p-[123I]iodo-L-phenylalanine (IPA), L-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and L-3-[123I]iodo-alpha-methyltyrosine (IMT) with regard to their uptake in human glioblastoma T99 and T3868 cells, and thereafter studied the mechanisms promoting the cellular uptake. The potential of the 123I-iodinated agents for use as SPET radiopharmaceuticals was evaluated in healthy experimental rats as well as in rats with stereotactically implanted C6 gliomas. The radiopharmaceutical uptake into glioblastoma cells was rapid, temperature and pH dependent, and linear during the first 5 min. Equilibrium was reached after 15-20 min, except in the case of ITIC, the initial uptake of which gradually decreased from 15 min onwards. The radioactivity concentration in glioma cells following 30-min incubation at 37 degrees C (pH 7.4) varied from 11% to 35% of the total activity per million cells (ITIC < IMT < or = IPA). Competitive inhibition experiments using alpha-(methylamino)-isobutyric acid and 2-amino-2-norbornane-carboxylic acid, known as specific substrates for systems A and L, respectively, as well as representative amino acids preferentially transported by system ASC, indicated that IPA, like IMT, is predominantly mediated by the L and ASC transport systems, while no significant involvement of the A transport system could be demonstrated. By contrast, none of the three principal neutral amino acid transport systems (A, L and ASC) appear to be substantially involved in the uptake of ITIC into glioblastoma cells. Analysis of uptake under conditions that change the cell membrane potential, i.e. in high K+ medium, showed that the membrane potential plays an important role in ITIC uptake. Alteration of the mitochondrial activity by means of valinomycin or nigericin induces a slight increase or decrease in the radiopharmaceutical uptake, suggesting a minor contribution of the mitochondria in the uptake. IPA, IMT and ITIC passed the blood-brain barrier, and thereafter showed efflux from the brain. The radioactivity concentration in healthy rat brain 15 min following intravenous injection varied from 0.07% (ITIC) to 0.27% ID/g (IPA). In comparison, the brain uptake in the stereotactically implanted C6 glioma rats was substantially higher (up to 1.10% ID/g 15 min p.i.), with tumour-to-background ratios greater than 4. These data indicate that IPA and ITIC, like IMT, exhibit interesting biological characteristics which hold promise for in vivo brain tumour investigations by SPET.

Alanine↗
PubMed2000

Tolerance-Inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning.

Many studies have reported ischemia protection using various preconditioning techniques, including single dose 3-nitropropionic acid (3-NPA), a mitochondrial toxin. However, the cellular signal transduction cascades resulting in ischemic tolerance and the mechanisms involved in neuronal survival in the tolerant state still remain unclear. The current study investigated the mRNA and protein expression of the antiapoptotic bcl-2 and the proapoptotic bax. two antagonistic members of the bcl-2 gene family, in response to a single dose of 3-NPA, to global cerebral ischemia-reperfusion. and to the combination of both 3-NPA-pretreatment and subsequent global cerebral ischemia-reperfusion. Brain homogenates of adult Wistar rats (n = 25) were analyzed for bcl-2 and bax mRNA expression using a new highly sensitive and quantitative polymerase chain reaction (PCR) technique that allows real-time fluorescence measurements of the PCR product (LightCycler; Roche Diagnostics, Mannheim, Germany). Animals for mRNA analysis received 3-NPA (20 mg/kg, intraperitoneal; "chemical preconditioning") or vehicle (normal saline), and were either observed for 24 plus 3 hours or were subjected to 15 minutes of global cerebral ischemia 24 hours after the pretreatment and observed for 3 hours of reperfusion. Immunohistochemistry was applied to serial brain sections of additional rats (n = 68) to determine amount and localization of the respective Bcl-2 and Bax protein expression in various brain areas. One set of animals was injected with 3-NPA and observed for 3, 12, 24, and 96 hours; a second set was exposed to 15 minutes global cerebral ischemia, 3, 12, and 24 hours reperfusion; and a third set was pretreated with 3-NPA or saline 24 hours before the ischemic brain insult and observed for 96 hours of reperfusion. The authors found single dose 3-NPA treatment to be associated with an elevated bcl-2:bax ratio (increased bcl-2 expression, decreased bax expression), both on the transcriptional (mRNA) and the translational (protein) level. The differential influence of 3-NPA was maintained during early recovery from global cerebral ischemia (3 hours), when 3-NPA pretreated animals showed higher bcl-2 and lower bax mRNA levels compared with rats with saline treatment. Respective changes in protein expression were localized predominately in neurons vulnerable to ischemic damage. Compared with baseline, Bcl-2 protein was significantly higher in surviving neurons at 96 hours after the insult, whereas Bax protein remained unchanged. However, at this late time of postischemic recovery (96 hours), the protein expression pattern of surviving neurons was not different between animals with and without 3-NPA pretreatment. To the authors' knowledge, the current study is the first report on the differential expression of pro- and antiapoptotic genes after a single, nonlethal dose of 3-NPA. The current results suggest alterations in the balance between pro- and antiapoptotic proteins as a potential explanation for the reported protection provided by chemical preconditioning using 3-NPA in rats.

Animals↗
PubMed2000

Significance of resting and stimulated cerebral blood flow for predicting the risk of hemodynamic cerebral ischemia in a model of chronic hemodynamic insufficiency.

OBJECTIVE: It has been postulated that patients with a compromised cerebrovascular reserve capacity (RC), defined as cerebral blood flow (CBF) response to acetazolamide (ACZ) (by percent), are at higher risk for ischemic stroke. The value of CBF and RC for predicting the risk of hemodynamically induced impairment of cerebral function is examined. METHODS: Both common carotid arteries were occluded in 22 Wistar-Kyoto rats. Thirty-one days later, mean arterial blood pressure was reduced to 40 mm Hg for 30 minutes. Laser Doppler scanning of CBF at resting conditions and after intraperitoneal administration of ACZ (0.1 mg/g body weight) was performed 30 minutes and 28 days after occlusion as well as before and during hypotension. Memory and motor functions were examined before and after CBF measurements. RESULTS: After occlusion, CBF dropped significantly and ACZ did not increase CBF. Four weeks later, resting CBF had significantly improved but remained impaired, as did RC, showing a distinct interindividual variability. Hypotension reduced CBF by 57 +/- 4% (P < 0.001) and significantly impaired memory and motor functions. CBF during hypotension correlated with resting CBF before hypotension (r = 0.495, P = 0.027) and with CBF before (r = 0.392, P = 0.048) and after (r = 0.476, P = 0.034) ACZ, as determined 4 weeks after occlusion. There was no correlation with RC (r = 0.091, P = 0.702). Neurological tests performed 1 day after hypotension correlated with CBF during hypotension (memory function, P = 0.03; motor function, P = 0.02) but not with RC. CONCLUSION: In this model of chronic hemodynamic insufficiency, the risk of impairment to global cerebral function was predicted by resting CBF and CBF after ACZ but not by RC determined with ACZ.

Acetazolamide↗
PubMed2000

Tightness of duraplasty in rabbits: a comparative study.

OBJECTIVE: The purpose of this study was to test, in rabbits, the tightness of seven dural substitution materials commonly used in neurosurgery, i.e., Lyodura (B. Braun Melsungen AG, Melsungen, Germany), Tutoplast dura (Tutogen Medical, Inc., Parsippany, NJ), Tutoplast fascia lata (Tutogen Medical, Inc.), autologous periosteum, Neuropatch (B. Braun Melsungen AG), Dacron (E.I. du Pont de Nemours and Co., Wilmington, DE), and Ethisorb (Ethicon, Inc., Somerville, NJ). METHODS: Duraplasties were performed with sutures alone or were additionally fixed with fibrin glue. Leakage pressures were assessed by infusion of artificial cerebrospinal fluid, containing sodium fluorescein, into the cisterna magna and detection of fluorescence using a charge-coupled display camera with background substraction, 3 days, 3 weeks, or 3 months after surgery. RESULTS: Three days after implantation, the mean tightness values of duraplasties with Lyodura or Neuropatch were significantly higher (P = 0.007) than the values for the other substitutes. A significant improvement of tightness with increasing implantation time could be demonstrated for autologous periosteum (P = 0.0063). Improvement of tightness with the use of fibrin glue could be proven only for the heterologous grafts (P = 0.0071). The tightness values for Neuropatch fixed only with sutures were similar to those for the best heterologous substitutes implanted with additional fibrin glue. Lyodura, Tutoplast dura, and Neuropatch demonstrated favorable implantation characteristics; they were thin, flexible, and easily suturable. Neither adhesions to the brain nor space-occupying scars were noted. CONCLUSION: These results confirm the excellent suitability of Lyodura and Neuropatch for dural substitution.

Animals↗
PubMed2000

Hypertonic/hyperoncotic resuscitation after intestinal superior mesenteric artery occlusion: early effects on circulation and intestinal reperfusion.

The objective of the study was to determine the early effects of hypertonic/hyperoncotic starch resuscitation after 2 h occlusion of the superior mesenteric artery (SMA) in comparison to animals reperfused without treatment and isotonic resuscitation. SMA was clamped (18 pigs, 19-23 kg) for 2 h followed by a 2-h reperfusion period, which was initiated with isotonic (ISO) (35 mL/kg 0.9% NaCl and 5 mL/kg 10% hydroxyethyl starch within 30 min) or hypertonic/hyperoncotic resuscitation (HHES) (7.5% NaCl/10% hydroxyethyl starch within 5 min). Cardiac output (CO), mean arterial blood pressure (MAP), serum lactate, antimesenteric serosal Laser-Doppler values (LD), and intramural pHi (tonometry) were measured. Without resuscitation at the onset of reperfusion MAP (70 +/- 3 mmHg) decreased to 40 +/- 3 mmHg and CO to 31% of baseline values after 30 min. Serum lactate increased to 5.1 +/- 1.6 mmol/L without improvement. The decrease of CO was attenuated only during the initial 30 min of reperfusion in the ISO group, but significantly better counteracted by hypertonic/hyperoncotic resuscitation. Without treatment, LD flow of the ileum (baseline 23-27 LD units) recovered but intramural pH (pHi) remained significantly decreased (7.26 +/- 0.05). With isotonic resuscitation LD values (21.8 +/- 2.1 LD units) and intramural pHi (7.09 +/- 0.14) decreased even more (P < 0.05) whereas the HHES group showed a significant hyperemic reaction and a normalization of the intramural pHi and serum lactate within 30 min. Hypertonic/hyperoncotic resuscitation significantly improves MAP and CO during reperfusion shock and induces an immediate hyperemic reperfusion reaction of the intestinal microcirculation. Adequate isotonic fluid replacement in order to restore the postischemic plasma volume loss may cause a pronounced deterioration of intestinal perfusion.

Animals↗
PubMed2000

Stimulatory effect of dexamethasone on angiotensin-converting enzyme in neonatal rat cardiac myocytes.

Angiotensin-converting enzyme (ACE) plays a central role in cardiac remodeling associated with pathological conditions such as myocardial infarction. The existence of different cell types in the heart expressing components of the renin-angiotensin system makes it difficult to evaluate their relative role under physiological and pathological conditions. Since myocytes are the predominant cellular constituent of the heart by mass, in the present study we studied the effects of glucocorticoids on ACE activity using well-defined cultures of neonatal rat cardiac myocytes. Under steady-state conditions, ACE activity was present at very low levels, but after dexamethasone treatment ACE activity increased significantly (100 nmol/l after 24 h) in a time-dependent fashion. These results demonstrate the influence of dexamethasone on ACE activity in rat cardiac myocytes. This is consistent with the idea that ACE activation occurs under stress conditions, such as myocardial infarction, in which glucocorticoid levels may increase approximately 50-fold.

Animals↗
PubMed2000

Ex vivo study of the physical effect of coils on pressure and flow dynamics in experimental aneurysms.

BACKGROUND AND PURPOSE: Recent experimental studies and a few case reports reveal that coiling may not lead to permanent occlusion of aneurysms by an organized thrombus. Therefore, biologic long-term prognosis seems to be doubtful, and the physical effect of coils may be important. The purpose of this study was to investigate the physical effect of coils on pressure and flow dynamics in aneurysms. METHODS: Bifurcation aneurysms were created in eight rabbits, explanted after 3 weeks, and tested in a model with pulsatile perfusion with 0.9% saline and heparinized blood. Before and after densely packing with coils, systemic and intraaneurysmal pressure, aneurysmal pulsation, and impact measurements were recorded. RESULTS: The peak and shape of the pressure waves in the aneurysm and in the delivery system were not significantly different before and after coiling. Under physiological intraaneurysmal pressure (while being perfused with saline), significant reduction (P = .022) of aneurysmal wall pulsation after coil embolization was noted. Overall, the aneurysmal impact on surrounding structures was statistically unchanged after coiling. However, in a few cases, after coil embolization, the observed increase of impact was more than doubled compared with the original values before coiling. CONCLUSION: Coils do not physically affect intraaneurysmal pressure. After coiling, there is no significant reduction of flow rates through the aneurysm and no reduction of aneurysmal impact, but aneurysmal wall pulsation may be decreased.

Animals↗
PubMed1999

Control of brain temperature during experimental global ischemia in rats.

Temperature control during experimental ischemia continues to be of major interest. However, if exposure of brain tissue is necessary during the experiment, regional heat loss may occur even when the core temperature is maintained. Furthermore, valid non-invasive brain temperature monitoring is difficult in small rodents. This paper describes a method for both monitoring and maintenance of brain temperature during small animal preparations in a stereotaxic frame. The device used includes an ear-bar thermocouple probe and a small near-infrared radiator. The new equipment permitted to maintain peri-ischemic brain temperature at a desired level while carrying out non-invasive continuous recordings of cerebral blood flow (laser Doppler-flowmetry) and of electrical brain function (EEG). In contrast, without extracranial heat application, superficial and basal brain temperatures decreased during global cerebral ischemia by 4.1 +/- 0.1 and 4.6 +/- 0.4 degrees C (mean +/- SEM), respectively, returning to baseline values at 15-30 min of reperfusion while rectal (core) temperature remained stable at baseline values. The ear-bar thermocouple probe (tympanic membrane) reliably reflected basal brain temperature, and temperature in superficial brain areas correlated well with that in the temporal muscle. Our data show that the new system allows to exclude unwanted hypothermic neuroprotection, and does not interfere with optical and electrical measurement techniques.

Animals↗
PubMed1999

C1-esterase inhibitor reduces infarct volume after cortical vein occlusion.

In order to clarify the role of complement as a mediator of cerebral infarct growth, we inhibited the classical complement activation pathway in a photochemical cortical vein occlusion model. Immediately after occlusion, rats were infused with either 0.9% saline (vehicle), or C1-esterase inhibitor (C1-INH) over 30 min. Regional cerebral blood flow (rCBF) decreased after occlusion, and was about 50% of baseline after 2 h. No difference was noted between experimental groups. Mean arterial blood pressure (MABP) and arterial blood gases were likewise unaffected by the treatment. However, administration of C1-INH had significantly reduced infarct volume by 72%, as evaluated after 5 days survival. Thus, the neuroprotective effect cannot be explained by an improvement of cerebral perfusion but rather by protection of the parenchyma in the penumbra.

Animals↗
PubMed1999

Modelling of the ischemic penumbra.

What happens to the ischemic penumbra--defined as a territory of critically reduced blood flow in the close neighborhood of an ischemic core--determines outcome after stroke. Currently the pathophysiology of the penumbra is studied predominantly in rat models with occlusion of the middle cerebral artery. Here we propose two other rat models with distinct advantages. One produces a large territory of critical flow reduction in the cortex of one hemisphere without presence of an infarct core: this model is suited to study mediator mechanisms that may transform the penumbra into necrotic tissue. It is produced by occluding one carotid artery and in addition reducing arterial pressure to 50 mm Hg using the hypobaric hypotension technique. Cortical flow is assessed by laser Doppler scanning. The second mode involves the photochemical occlusion of two adjacent cortical veins and goes along with a rather widespread reduction of cortical flow and the development of small infarcts of 2-5 mm3 infarct volume. Like the first model it is suited to administer mediators causing the infarct to grow in size, and thereby to evaluate the pathophysiologic significance of individual mediator mechanisms. In addition the model can be used to study specific therapeutic approaches.

Animals↗
PubMed1999

Surgical procedure affects physiological parameters in rat myocardial ischemia: need for mechanical ventilation.

Several surgical approaches are being used to induce myocardial ischemia in rats. The present study investigated two different operative procedures in spontaneously breathing and mechanically ventilated rats under sham conditions. A snare around the left coronary artery (LCA) was achieved without occlusion. Left lateral thoracotomy was performed in spontaneously breathing and mechanically ventilated rats (tidal volume 8 ml/kg) with a respiratory rate of 90 strokes/min at different levels of O2 supplementation (room air and 30, 40, and 90% O2). All animals were observed for 60 min after thoracotomy. Rats operated with exteriorization of the heart through left lateral thoracotomy while breathing spontaneously developed severe hypoxia and hypercapnia despite an intrathoracic operation time of <1 min. Arterial O2 content decreased from 18.7 +/- 0.5 to 3.3 +/- 0.9 vol%. Lactate increased from 1.2 +/- 0.1 to 5.2 +/- 0.3 mmol/l. Significant signs of ischemia were seen in the electrocardiogram up to 60 min. Mechanically ventilated animals exhibited a spectrum ranging from hypoxia (room air) to hyperoxia (90% O2). In order not to jeopardize findings in experimental myocardial ischemia-reperfusion injury models, stable physiological parameters can be achieved in mechanically ventilated rats at an O2 application of 30-40% at 90 strokes/min.

Animals↗
PubMed1998

In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid.

Several malignant tissues synthesize endogenous porphyrins after exposure to 5-aminolevulinic acid (5-ALA). The present experiments have been designed to elucidate whether the C6 glioma cell, a model cell for human malignant glioma, similarly synthesizes porphyrins when exposed to 5-ALA, and whether specific synthesis occurs when C6 cells are inoculated into rat brains to form a tumor. In this situation the blood-brain barrier may interfere with 5-ALA availability, and spreading of porphyrins with edema outside the tumor may occur. Flow cytometry is used to determine the course of cell volume and porphyrin fluorescence intensities in cultured C6 cells which are incubated in 1 mM 5-ALA. For the induction of experimental brain tumors, 10(4) untreated C6 cells are inoculated into the brains of rats. After 9 days animals receive 100 mg 5-ALA/kg body weight. Brains are removed after 3, 6, or 9 h and frozen coronal sections obtained for H/E staining or fluorescence spectography. Cultured C6 cells show a linear increase of protoporphyrin IX fluorescence after exposure to 5-ALA, which begins to plateau after 85 min. Marked fluorescence is also observed in solid and infiltrating experimental tumor. However, faint fluorescence also occurs in normal tissue, basal pia, choroid plexus, and, more obviously, in white-matter tracts bordering the tumor (maximal distance: 1.5 +/- 0.7 mm). The observations demonstrate that C6 cells synthesize protoporphyrin IX after exposure to 5-ALA in vitro and in vivo. However, when utilizing 5-ALA for fluorescence detection or photodynamic therapy of brain tumors, attention should be paid to the possibility of protoporphyrin IX occurring outside the tumor.

Aminolevulinic Acid↗
PubMed1998

Superior sagittal sinus thrombosis: a clinical and experimental study.

Sinus-vein thrombosis is increasingly recognized as a much more frequent neurological disorder than was anticipated before. We examined the pathophysiology of superior sagittal sinus thrombosis (SSST) from 19 patients and a rat SSST model. We treated 19 cases with SSST who were diagnosed by angiography. The symptoms of nine patients, who suffered multiple intracerebral hemorrhage, were abrupt. In another ten patients who recovered satisfactorily, the condition progressed slowly and they were treated with heparin and urokinase. Multivariate analysis demonstrated that female, sudden onset (<24 hours) and posterior 1/3 occlusion are related to bad outcome. Experimentally, SSST was induced by ligation and slow injection of kaolin-cephalin suspension into SSS in rats. Regional cerebral blood flow (rCBF) and tissue hemoglobin oxygen saturation (Hb Sao(2)) using a "scanning" technique were measured at 48 locations, and fluorescence angiography was performed before and until 90 min after SSST induction. After 48 hours the animals were sacrificed for histological studies. Decrease of rCBF and tissue Hb SO(2) and brain damage were seen in group B (n = 10) with an extension of thrombosis from SSS into cortical veins. Brain injury was not observed in group A (n = 8) with SSS thrombus alone and sham-operated animals (n = 5). In conclusion, a brain with acute extension of thrombus from SSS into cortical veins becomes critical for cerebral blood supply and metabolism. CBF, tissue HbSO(2) and repeated angiography can be helpful monitors for the early detection of critical conditions after SSST. As to the therapy, restraint on the ongoing thrombus is essential to protect the brain with SSST, and we encourage the use of combination therapy of heparin and urokinase as early as possible in cases without intracerebral hemorrhage.

Journal Article↗
PubMed1998

Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats.

BACKGROUND AND PURPOSE: An animal model of incomplete forebrain ischemia resembling human hemodynamic insufficiency was established. The model allows examination of acute and chronic changes of local cerebral blood flow (lCBF) and reserve capacity in correlation with behavioral parameters. METHODS: Anesthetized male Wistar-Kyoto rats underwent bilateral carotid occlusion (BCO). Laser-Doppler scanning of lCBF at baseline conditions and after acetazolamide was done 30 minutes after BCO, motor and memory function tests were administered after 1 and 2 days, and both investigations were repeated after 1, 2, 4, and 6 weeks. A sham-operated and a control group without any vessel manipulation served as controls. RESULTS: lCBF dropped within 60 minutes after surgery by 62% (P<0.001) in 10 animals surviving BCO (BCOsurvival) and by 69% in 5 rats that died within 9 days (BCOlethal). Acetazolamide increased lCBF to 142.33% in controls, to 136.66% in sham-operated rats (both significant), and to 104.80% in BCOsurvival (not significant), and it decreased flow by 23.1% in BCOlethal rats (P<0.001). Baseline lCBF normalized within 4 weeks. Total motor function scores were significantly reduced from 9 points preoperatively to 5.80+/-0.65 in BCOlethal and 6.68+/-0.54 points in BCOsurvival rats 1 day after occlusion. Memory retention function remained impaired after BCO, as did the acetazolamide response, which correlated with motor score and was inversely related to maze exploration time. CONCLUSIONS: This model allows long-term follow-up of cerebral function, lCBF, and reserve capacity in a pathophysiological setting similar to hemodynamic insufficiency in humans.

Acetazolamide↗
PubMed1998

Postischemic application of lipid peroxidation inhibitor U-101033E reduces neuronal damage after global cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The lipid peroxidation inhibitor U-101033E was examined for effects on cerebral blood flow (CBF), cortical tissue hemoglobin oxygen saturation (HbSo2), and neuronal damage. METHODS: Fifteen minutes of global cerebral ischemia was induced by two-vessel occlusion and hypobaric hypotension. Wistar rats (n = 25) were randomized to receive vehicle (n = 9) or 40 mg/kg U-101033E (n = 9) intraperitoneally during 2 hours of reperfusion. A sham group (n = 7) had neither ischemia nor therapy. Histology was evaluated 7 days after ischemia. RESULTS: During late hyperperfusion (at 17 minutes), vehicle-treated animals had a higher (P = 0.044) cortical tissue HbSo2 (72.0 +/- 1.4%) than did U-101033E-treated animals (65.8 +/- 2.5%). Neuronal counts in the superficial cortex layer found after 7 days correlated negatively with rCBF (r = -0.76; P < 0.001) or cortical tissue HbSo2 (r = -0.56; P = 0.028) assessed during the late hyperperfusion phase. U-101033E reduced neuronal damage in hippocampal CA1 from 64.3 +/- 9.2% to 31.2 +/- 8.4% (P = 0.020), as well as in the superficial cortical layer from 53.5 +/- 14.6% to 12.8 +/- 11.7% (P = 0.046). While animals in the vehicle group had reduced counts in all four examined cortex layers (P < 0.05 versus sham group), there was significant cortical neuron loss in the U-101033E group in only one of four areas. U-101033E had no effect on resting CBF or CO2 reactivity. CONCLUSIONS: Postischemic application of U-101033E protects hippocampal CA1 and cortical neurons after 15 minutes of global cerebral ischemia. The results indicate that free radical-induced lipid peroxidation contributes to reperfusion injury, a process that can be inhibited by antioxidants such as U-101033E.

Animals↗
PubMed1997

Intracoronary application of C1 esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion.

BACKGROUND: Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events, including complement activation, leukocyte adhesion, and infiltration and release of diverse mediators, probably play important roles. The present study addresses the possibility of reducing reperfusion damage by the application of C1 esterase inhibitor (C1-INH). METHODS AND RESULTS: Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1-INH was administered during the first 5 minutes of coronary reperfusion Compared with the NaCl controls, C1-INH reduced myocardial injury (48.8 +/- 7.8% versus 73.4 +/- 4.0% necrosis of area at risk, P < or = .018). C1-INH treatment significantly reduced circulating C3a and slightly attenuated C5a plasma concentrations. Myocardial protection was accompanied by reduced plasma concentration of creatine kinase and troponin-T. C1-INH had no effect on global hemodynamic parameters, but local myocardial contractility was markedly improved in the ischemic zone. In the short-axis view, 137 degrees of the anteroseptal region showed significantly improved wall motion at early and 29 degrees at late reperfusion with C1-INH treatment. CONCLUSIONS: C1-INH significantly protects ischemic tissue from reperfusion damage, reduces myocardial necrosis, and improves local cardiac function.

Anaphylatoxins↗
PubMed1997

Microcirculation after cerebral venous occlusions as assessed by laser Doppler scanning.

Research on cerebral venous circulation disturbances (CVCDs) has been limited partly by the paucity of animal models that produce consistent venous infarction. Occlusion of two adjacent cortical veins in rats by means of a photochemical thrombotic technique provides a minimally invasive, clinically relevant, and reproducible model suited to study the pathophysiology of CVCDs. In this study, the effects of venous occlusion on regional cortical blood flow and the brain damage that ensues were evaluated. Cortical vein occlusion was induced by photoactivation of rose bengal via 100-microm fiberoptic illumination. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after venous occlusion, and regional cerebral blood flow (rCBF) was determined at 48 locations by using laser Doppler scanning. Histological damage was assessed 48 hours after vein occlusion. Occlusion of two cortical veins (Group T; seven animals) was compared with single-vein occlusion and its ensuing brain damage (Group S; five animals) and with sham-operated control (five animals). An rCBF reduction occurred 30 minutes after occlusion in Group T and was more extensive than the decrease in Group S after 60 minutes. Observation frequency histograms based on local CBF data obtained in Group T demonstrated that local CBF at some sites decreased to a level below the ischemic threshold within 90 minutes. Six of the seven rats in Group T had a growing venous thrombus with extravasation of fluorescein. The resulting infarction was significantly larger in Group T (9.8 +/- 4.5% of the hemispheric area) than in Group S (only 3 +/- 1.5% of the hemispheric area). In conclusion, microcirculation perturbations occur early after venous occlusion and result in the formation of a venous thrombus accompanied by local ischemia and severe venous infarction. The extent of vein occlusion determines the resulting brain damage. Based on the results of this study, the authors conclude that CVCDs may be attenuated by prevention of venous thrombus progression together with the use of protective measures against the consequences of ischemia.

Animals↗