Biomedical subjects

A Heimann

Publications and source records attributed to A Heimann.

At least 19 recordsLinked to original sources

PubMed2006

Caspase-dependent cell death involved in brain damage after acute subdural hematoma in rats.

Traumatic brain injury is associated with acute subdural hematoma (ASDH) that worsens outcome. Although early removal of blood can reduce mortality, patients still die or remain disabled after surgery and additional treatments are needed. The blood mass and extravasated blood induce pathomechanisms such as high intracranial pressure (ICP), ischemia, apoptosis and inflammation which lead to acute as well as delayed cell death. Only little is known about the basis of delayed cell death in this type of injury. Thus, the purpose of the study was to investigate to which extent caspase-dependent intracellular processes are involved in the lesion development after ASDH in rats. A volume of 300microL blood was infused into the subdural space under monitoring of ICP and tissue oxygen concentration. To asses delayed cell death mechanisms, DNA fragmentation was measured 1, 2, 4 and 7 days after ASDH by TUNEL staining, and the effect of the pan-caspase inhibitor zVADfmk on lesion volume was assessed 7 days post-ASDH. A peak of TUNEL-positive cells was found in the injured cortex at day 2 after blood infusion (53.4+/-11.6 cells/mm(2)). zVADfmk (160ng), applied by intracerebroventricular injection before ASDH, reduced lesion volume significantly by more than 50% (vehicle: 23.79+/-7.62mm(3); zVADfmk: 9.06+/-4.08). The data show for the first time that apoptotic processes are evident following ASDH and that caspase-dependent mechanisms play a crucial role in the lesion development caused by the blood effect on brain tissue.

Amino Acid Chloromethyl Ketones↗

PubMed2005

Brain oxygen monitoring: in-vitro accuracy, long-term drift and response-time of Licox- and Neurotrend sensors.

BACKGROUND: Oxygen tension sensors have been used to monitor tissue oxygenation in human brain for several years. The working principals of the most frequently used sensors, the Licox (LX) and Neurotrend (NT), are different, and they have never been validated independently for correct measurement in vitro. Therefore, we tried to clarify if the two currently available sensors provide sufficient accuracy and stability. METHOD: 12 LX oxygen tension sensors and NT sensors were placed into a liquid-filled tonometer chamber. The solution was kept at 37 +/- 0.2 degrees C and equilibrated with five calibration gases containing different O(2)- and CO(2)-concentrations. After equilibration, readings were taken for each gas concentration (accuracy test). Afterwards, the sensors were left in 3% O(2) and 9% CO(2) and readings were taken after 24, 48, 72, 96 and 120 hours (drift test). Thereafter, a 90% response time test was performed transferring sensors from 1% to 5% oxygen concentration and back, using pre-equilibrated tonometers. FINDINGS: All Licox oxygen probes [12] were used for this study. Two of 14 Neurotrend sensors did not calibrate, revealing a failure rate of 14% for NT. Oxygen tension during the accuracy test was measured as follows: 1% O(2) (7.1 mmHg): LX 6.5 +/- 0.4, NT 5.3 +/- 2.3 mmHg, 2% O(2) (14.2 mmHg): LX 12.9 +/- 0.6, NT 12.1 +/- 2.2 mmHg, 3% O(2) (21.4 mmHg): LX 19.8 +/- 0.7, NT 19.4 +/- 2.4 mmHg, 5% O(2) (35.8 mmHg): LX 33.4 +/- 1.0 mmHg, NT 33.5 +/- 2.9 mmHg, 8% O(2) (57.0 mmHg): 53.8 +/- 1.5, NT 53.6 +/- 3.3 mmHg. After 120 hours in 3% O(2) (21 mmHg), LX measured 19.8 +/- 1.9 mmHg, NT 17.9 +/- 4.7 mmHg. 90% response time from 1% to 5%/5% to 1% oxygen concentration was 129 +/- 27/174 +/- 26 sec for LX, 55 +/- 19/98 +/- 39 sec for NT. CONCLUSIONS: Both systems are measuring oxygen tension sufficiently, but more accurately with LX probes. NT sensors read significantly lower pO(2) in 1% O(2) and show an increasing deviation with higher oxygen concentrations which was due to two of twelve probes. A slight drift towards lower oxygen tension readings for both sensors but more pronounced for the NT does not impair long-term use. NT measures pCO(2) and pH very accurately.

Brain↗

PubMed2004

Pharmacological preconditioning in global cerebral ischemia.

Single dose 3-nitropropionic acid (3-NPA) 24 hr before global ischemia improves neuronal survival in both, neocortex and hippocampus ('chemical preconditioning'). Neuronal survival after transient global ischemia requires new protein synthesis during recovery, especially of those with anti-apoptotic function. Bcl-2-protein is expressed in neurons that survive cerebral ischemia and may parallel the time course of tolerance after ischemic preconditioning. With this study we examined whether differences in bcl-2-protein expression compared to baseline may be involved in the induction of ischemic tolerance using 3-NPA. Male Wistar rats received either a single intraperitoneal (i.p.) dose of 3-NPA (20 mg/kg), and were observed for 3 (n = 4), 12 (n = 5) or 24 hours (n = 5) or the same amount of vehicle and were observed for 24 h (n = 8, controls). Immunohistochemistry allowed to compare the intensity of bcl-2 immunoreactivity at three subsequent time points in hippocampus, dentate gyrus and parietal neocortex with that of control animals. A single dose of 3-NPA caused a significant increase of bcl-2 protein immunoreactivity in hippocampal neurons, i.e. CA 1 (5 out of 5 animals, p = 0.003), CA 3 (5/5, p = 0.003), CA 4 (4/5, p = 0.025), and neocortex (5/5, p = 0.004), in a time dependent manner over a period of 24 hr after injection. Neuronal bcl-2 protein expression in CA 2 and dentate gyrus remained unchanged. The data suggest a possible role of bcl-2-protein in chemical induction of ischemic tolerance using a single subtoxic dose of 3-NPA. Bcl-2-protein expression may be initiated by increased levels of reactive oxygen species (ROS) after 3-NPA administration, as shown by others. Additional bcl-2 protein may then be available to (1) control postischemic ROS burst, (2) protect the mitochondrial membranes, and (3) inhibit pro-apoptotic mechanisms.

Adaptation, Physiological↗

PubMed2003

Effects of hypertonic/hyperoncotic treatment after rat cortical vein occlusion.

OBJECTIVE: To examine the effects of hypertonic/hyperoncotic treatment on physiologic variables and regional cerebral blood flow and to test its neuroprotective efficiency in a model of permanent venous ischemia. DESIGN: Randomized prospective study. SETTING: University research institute. SUBJECTS: Adult male Wistar rats, weighing 359 +/- 54 g (n = 38). INTERVENTIONS: Rats were subjected to photochemical occlusion of two adjacent cortical veins. A randomized infusion with vehicle (0.9% NaCl), 10% hydroxyethyl starch 200,000 (HES), or 7.5% saline plus 10% hydroxyethyl starch 200,000 (HHES) was started 30 mins after two-vein occlusion. Effects on physiologic variables and regional cerebral blood flow (assessed by laser Doppler flowmetry) were studied up to 120 mins after two-vein occlusion. Two days after occlusion, the brains were removed for histologic evaluation. MEASUREMENTS AND MAIN RESULTS: After occlusion, regional cerebral blood flow decreased by 50%, significantly in all groups (from 47.3 +/- 3 to 22.2 +/- 2.2 laser Doppler units). In the vehicle and HES groups, regional cerebral blood flow further decreased to 12.9 +/- 1.9 and 17.8 +/- 2.3 laser Doppler units, respectively. HHES improved regional cerebral blood flow significantly to 27.3 +/- 3.5 laser Doppler units, particularly by reducing no-flow/low-flow areas and reducing infarct size. CONCLUSION: We found that HHES reduced infarct size as a consequence of an improved regional cerebral blood flow and reduced no-flow/low-flow areas in the tissue at risk in the two-vein occlusion model.

Animals↗

PubMed2003

Novel complement C1 inhibitor BSF468248 does not improve brain damage after cortical vein occlusion.

BSF468248 is a novel potent complement C1 inhibitor. To determine whether BSF468248 is effective against focal cerebral ischemia, we evaluated the change of cerebral blood flow (CBF) and infarction volume using a photochemically-induced cortical vein occlusion model in rats in blind studies. In 22 Wistar rats, two adjacent cortical veins were occluded by photochemical thrombosis and fiberoptic illumination under controlled anesthesia and ventilation. Just after the occlusion, BSF468248 or physiological saline was administrated. In the low-dose study, a treatment group (n = 7) was administered BSF468248 1 mg/kg bolus and 1 mg/kg continuously for 30 min. The same volume of saline was given to a vehicle group (n = 5). In the high-dose study, a treatment group (n = 5) was administrated BSF468248 1 mg/kg bolus and 12 mg/kg continuously for 180 min. The same volume of saline was given to a vehicle group (n = 5). During the experiment, regional cerebral blood flow (rCBF) was measured in both the low-dose study (120 min) and the high-dose study (180 min). Seven days after the experiment, the animals were killed in order to evaluate the infarct volume. The rCBF at the end of the experiment showed a similar decrease in both the low-dose study (at 120 min: treatment group: 66.5 +/- 10.2%; vehicle group: 69.3 +/- 10.2%) and the high-dose study (at 180 min: treatment group: 62.1 +/- 7.5%; vehicle group: 65.1 +/- 12.3%), with no significant differences (t-test). The infarct volume also showed no significant difference in either group of the low-dose study (treatment group: 3.46 +/- 0.84 mm3; vehicle group: 3.56 +/- 1.40 mm3) or the high-dose study (treatment group: 2.27 +/- 0.43 mm3; vehicle group: 1.76 +/- 0.31 mm3). Our study found that BSF468248 is not effective in improving the rCBF and the infarct volume following focal cerebral ischemia.

Animals↗

PubMed2002

Experimental research photodynamic effects in perifocal, oedematous brain tissue.

BACKGROUND: Photodynamic therapy (PDT) has been under discussion as additional treatment option for malignant gliomas. However, damage not only to tumour tissue but also to normal brain has been demonstrated. The mechanisms of this unwanted side effect have not yet been clearly identified. Spreading of photosensitiser with oedema after disruption of the blood-brain-barrier and potential sensitisation of normal tissue has been found previously. The present study investigates the time- and dose-dependency of normal tissue damage to photodynamic therapy using Photofrin II after disruption of the blood-brain-barrier. METHODS: Male wistar rats anaesthetised with chloral hydrate were subjected to focal, cerebral cold lesions. Simultaneously, Photofrin II (PFII) was injected (2,5 or 5 mg/kg b.w.). Laser irradiation (630 nm) was performed after 4 h, 12 h and 24 h with varying light doses. Control groups were subjected to focal cold lesion alone, cold lesion with laser irradiation, PFII followed by laser irradiation, or laser irradiation alone (n=6 all groups). 24 h later, brains were removed for assessment of necrosis in coronal sections. FINDINGS: Light dose had a significant impact on the extent of necrosis. Compared to control animals (lesion only: 0.84 +/- 0.2 mm2; lesion and irradiation alone: 0.7 +/- 0.3 mm2), the area of necrosis was increased to 2.8 +/- 0.5 (50 J/cm2), 3.5 +/- 1,1 (100 J/cm2) and 4.3 +/- 0.7 mm2 (200 J/cm2, 5 mg/kg b.w.; p<0.01). This effect was time-dependent. Maximal necrosis (6.3 +/- 1,6 mm2) was observed when brains were irradiated 12 h after PFII injection, with less necrosis occurring at 24 h (2.8 +/- 0.4 mm2, p<0.01). Reducing sensitiser dose to 2.5 mg/kg b.w. resulted in a reduction of necrosis (2.09 +/- 0.2 mm2, p<0.05). INTERPRETATIONS: Damage to oedematous tissue after photodynamic therapy using i.v. PFII and laser light at 630 nm depends on laser dose, sensitiser dose and the time point of laser irradiation. The time point of PDT should be considered to prevent unwanted tissue reactions. In the clinical setting however, defined damage to peritumoural tissue may be advantageous. This should be achievable by optimised timing and dosage of photodynamic therapy.

Animals↗

PubMed2001

Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects.

BACKGROUND: Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH. METHODS AND RESULTS: Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a dose of 40, 100, and 200 IU/kg body wt. Compared with the NaCl controls, C1-INH 40 IU/kg reduced myocardial injury (44.1+/-13.8% versus 76.7+/-4.6% necrosis of area at risk, P</=0.05) and significantly suppressed local C3a and C5a generation. Myocardial protection was accompanied by reduced plasma concentrations of creatine kinase and troponin T. In contrast, no beneficial effects were observed when 100 IU/kg C1-INH was used. Furthermore, application of 200 IU/kg C1-INH provoked severe side effects and coagulation disorders. CONCLUSIONS: When applied at the correct dose, C1-INH significantly protects ischemic tissue from reperfusion damage. However, overly high doses (>/=100 IU/kg) of C1-INH will provoke detrimental side effects, probably via its procoagulatory action.

Anaphylatoxins↗

PubMed2001

Nitric oxide modulates cerebral blood flow stimulation by acetazolamide in the rat cortex: a laser Doppler scanning study.

The involvement of nitric oxide (NO) in cerebral blood flow (CBF) stimulation by acetazolamide was studied in anaesthetised, mechanically ventilated Wistar rats. CBF was monitored by laser Doppler scanning. Acetazolamide induced a long-lasting significant rCBF-increase. Application of NG-Nitro-L-arginine (L-NNA), an inhibitor of all NO synthetases (NOS), prevented CBF stimulation by acetazolamide. Continuous infusion of the exogenous NO donor SIN-1 (3-morpholinosydnonimine) suppressed L-NNA induced increases of mean arterial blood pressure without effect on rCBF in comparison to baseline. Additional acetazolamide injection then again caused a significant increase of rCBF in spite of NOS-inhibition. We thus conclude that NO is involved in acetazolamide-induced CBF stimulation. The mere continuous presence of NO is sufficient to re-establish the acetazolamide-response in spite of NOS-inhibition. These data suggest that NO acts rather as a modulator than as a mediator of the acetazolamide-induced CBF response.

Acetazolamide↗

PubMed2001

On the number of measurement sites required to assess regional cerebral blood flow by laser-Doppler scanning during cerebral ischemia and reperfusion.

The aim of this study was to determine whether the number of measurement sites affected the precision of regional cerebral blood flow (CBF) assessment by Laser-Doppler (LD). A simulation study was applied based on data obtained by scanning the cortex in 25 rats during baseline conditions, 15 min global cerebral ischemia and reperfusion. Random samples were repeatedly collected from 1 to 100 locations and deviations from the median of the entire CBF data pool (800 locations) were determined. Single location CBF measurements missed the true median by 24.8+/-2.2 LD-units (baseline conditions, n=100 simulations, mean+/-SEM), 2.7+/-0.6 LD-units (ischemia), and 31.9+/-2.4 LD-units (30th min reperfusion), which can be reduced to 10.9+/-1.0 LD-units (baseline), 0.9+/-0.1 LD-units (ischemia), and 15.5+/-1.3 LD-units (30th min reperfusion) by scanning ten locations. Reliability is further improved by scanning 30 sites with deviations of 6.1+/-0.6 LD-units (baseline), 0.4+/-0.0 LD-units (ischemia), and 8.9+/-0.7 LD-units (30th min reperfusion). Single location CBF assessment was sufficient during global ischemia only. In order to keep the deviation from the true flow below 10 LD-units, at least 15 locations are recommended during baseline conditions and 25 during reperfusion. Laser-Doppler scanning improves the reliability and reduces the variability of CBF measurements.

Animals↗

PubMed2001

Neuroprotection of S(+) ketamine isomer in global forebrain ischemia.

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can block the action of excitotoxic amino acids in the central nervous system. S(+) ketamine has a 2-3 times higher anesthetic potency compared with the ketamine-racemate and also shows a higher neuroprotective efficacy in vitro. To determine the neuroprotective activity of S(+) ketamine compared with its R(-) stereoisomer in vivo, we examined the functional and neurohistological outcome in rats treated 15 min after global forebrain ischemia with S(+) ketamine in different dosages compared with R(-) ketamine. Influence of the treatment on regional cerebral blood flow (rCBF) and cortical oxygen saturation (HbO2) was monitored over 1 h after the ischemia using laser doppler flowmetry and microphotospectrometry respectively. Sixty and ninety mg/kg of S(+) ketamine but not R(-) ketamine significantly reduced neuronal cell loss in the cortex compared with the saline treated group. No significant neuroprotection was observed in the hippocampus. Although no significant change in rCBF was found, S(+) ketamine restored the cortical HbO2 to preischemic values. These results indicate that S(+) ketamine in higher dosages can reduce neuronal damage in the cortex after cerebral ischemia, possibly by improving the ratio of oxygen supply to consumption in the postischemic tissue.

Animals↗

PubMed2001

C1-esterase-inhibitor treatment at early reperfusion of hemorrhagic shock reduces mesentry leukocyte adhesion and rolling.

OBJECTIVE: Complement activation probably plays a pathogenic role in multiple organ failure in shock. This study evaluates the effects of C1-esterase-inhibitor treatment on leukocyte-endothelial interaction in the mesenteric microcirculation in hemorrhagic shock. METHODS: Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body wt. for 60 minutes) followed by a 4-hour reperfusion period. C1-INH (100 IU/kg body wt. i.v.) or 0.9% NaCl i.v. were administered as a bolus at the beginning of reperfusion. Reperfusion time mimicked a "pre-hospital" phase of 30 minutes followed by a quasi "in-hospital" phase of 3.5 hours. The "in-hospital" phase was initiated by substitution of blood followed by fluid resuscitation with normal saline. RESULTS: Application of C1-INH markedly reduced rolling and adherent leukocytes to numbers approaching baseline values. Vmax and shear rate of the mesenteric microcirculation improved in both groups after reperfusion with a trend to higher values in the C1-INH group (n.s. p = 0.08). CONCLUSION: C1-INH applied in a bolus dose of 100 IU/kg body wt. i.v. abrogated enhanced leukocyte adhesion and rolling in the mesenteric microcirculation after hemorrhagic shock. Single bolus treatment with a complement inhibitor may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.

Animals↗

PubMed2001

Microcirculatory alterations in a Mongolian gerbil sinus-vein thrombosis model.

BACKGROUND AND PURPOSE: The pathophysiology of sinus vein thrombosis (SVT) is still controversial in patients and experimental animals, the microcirculatory alterations in particular. This study was designed to develop a new sinus vein thrombosis model and to further elucidate pathophysiological events such as the relationship between local and regional cerebral blood flow and haemoglobin oxygen saturation (HbSO2), changes of the microvasculature, leukocyte behaviour and brain tissue damage. METHODS: In a first experimental series, animals were divided into two groups which resulted from different procedures of inducing SVT. In the SSS middle occlusion group (SMO group), SVT was induced by the ligation of the superior sagittal sinus right in the middle between the bregma and the confluence sinum. In the SSS posterior occlusion group (SPO group) the ligation was performed close to the confluence sinum. Regional cerebral blood flow (rCBF) was assessed at 36 identical locations by laser Doppler flowmetry together with regional haemoglobin oxygen saturation (HbSO2). In a second series of experiments SVT was induced by ligation of the SSS close to the confluence sinum (SVT group) to study effects on the cortical microcirculation. A sham operation was performed in six animals (sham group). In both groups, an intravital microscopic double tracing technique was utilised for evaluating microvessel structures and leukocyte behaviour. The images were recorded on videotape for evaluating alterations of microvessel (venules, arterioles and capillaries) diameters and numbers of leukocyte rollers and stickers by a digital video analyser. Animals were sacrificed for histological evaluation after 5 days. RESULTS: The posterior sinus ligation caused a significant decrease of rCBF and HbSO2 and brain tissue damage which was not seen in the SMO group. Alteration of rCBF and HbSO2 were positively correlated with infarct size in the SPO group only, where venous infarction was easily reproduced. Therefore, it is suggested that this model is suitable for studying SVT in Mongolian gerbils. Intravital microscopy of the cortical microcirculation revealed no significant changes of vessels diameter in the sham group, whereas a significant dilation of veins and capillaries was seen in the SVT group. Numbers of leukocyte rollers and stickers were positively correlated with infarct size. CONCLUSION: Microcirculatory alterations and brain tissue damage from SVT in the Mongolian gerbil depend on the SSS occlusion site. The newly established mongolian gerbil sinus-vein thrombosis model has advantages compared to previously reported sinus-vein thrombosis models such as easy handling, easy technique, highly reproducibility, and good observation of microcirculatory event. The model allows for studies of cerebral low-flow conditions such as expected to occur in an ischaemic penumbra zone.

Animals↗

PubMed2001

Plasma protein loss during surgery: beneficial effects of albumin substitution.

Plasma protein loss during abdominal surgery is a known phenomenon, but its possible pathophysiological relevance has remained unknown. The present study evaluates the effects of albumin substitution on systemic and local hemodynamics and cellular interactions in the mesenteric microcirculation. Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Plasma protein concentrations, systemic and local hemodynamics were recorded during the follow up period, with or without albumin substitution. Depending on the time course of plasma protein loss in control experiments, 80% of the calculated protein loss was infused during the first 2 h of surgery, and the other 20% over the following 5 h of intravital microscopy. The control group received a continuous infusion of normal saline. Plasma protein loss was mainly due to loss of albumin. A significant increase in adherent and rolling leukocytes was observed during the course of mesenteric exteriorization, which was almost entirely reversed by albumin replacement. Albumin substitution led to stabilisation of mean arterial pressure and abdominal blood flow and also attenuated reductions in arterial base excess. Albumin infusions to replace plasma protein loss may be a simple and effective measure to attenuate microcirculatory disturbances and may be of benefit in patients undergoing abdominal surgery.

Abdomen↗

PubMed2000

Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial inhibitor.

It was studied whether a subtoxic dose of the mitochondrial neurotoxin, 3-nitropropionic acid (3-NPA), can initiate early-onset tolerance induction for subsequent ischemic injury. Wistar rats were pretreated for 3 h by intraperitoneal 3-NPA (20 mg/kg body weight; n=13) or solvent (n=12). Fifteen minutes global cerebral ischemia was induced by bilateral carotid artery occlusion and hypobaric hypotension. rCBF and tissue hemoglobin oxygen saturation were measured by laser Doppler scanning and a microspectrophotometric method. Ischemic insult and brain temperature were identical in both groups. Body weight and neurological scores recovered in the pretreated group but further deteriorated in the non-treated group (P<0.05). Quantitative histology demonstrated a better neuronal density in neocortex and hippocampal CA2, CA3, and CA4 of pretreated animals (P<0.05).

Animals↗

PubMed2000

Effects of cortical spreading depression on cortical blood flow, impedance, DC potential, and infarct size in a rat venous infarct model.

A cortical venous infarction model has been evaluated as to the degree of regional flow reduction and by studying effects of cortical spreading depression (CSD). Two adjacent cortical veins were occluded photochemically with rose bengal and fiberoptic illumination. Seven rats served to demonstrate effects on regional cortical blood flow using laser Doppler scanning. In 36 rats local CBF, DC potential, and brain tissue impedance were measured continuously for 75 min after vein occlusion. No, 3, or 10 CSD waves were induced by potassium chloride injection during the initial 75 min. Rats were compared for spontaneous CSDs; baseline local CBF, CBF, and impedance response to CSD; and infarct volume. Seventy-five minutes after vein occlusion regional cortical flow in a 3.5x7-mm window was reduced to 34.3+/-13.2%. At 45% of the 840 measured locations in 7 rats flow was <40% baseline and at 27.3% <30%, indicating a widespread penumbra territory. During the initial 75 min 2.1+/-1.1 spontaneous CSDs were observed. There was a positive correlation between the number of spontaneous CSDs seen acutely and infarction volume after 5 days. Moreover, brain injury was significantly increased in the group with 10 KCl-induced CSDs. A reduced 1CBF response and an overshooting tissue impedance change during CSD were predictors of ischemic damage. This study demonstrates a CSD-related growth of the venous infarct. Second, the data indicate that flow after two-vein occlusion resembles that seen under penumbra conditions, allowing for studies of damage mechanisms responsible for infarct growth.

Acute Disease↗

PubMed2000

Plastic foil technique attenuates inflammation in mesenteric intravital microscopy.

BACKGROUND: Interpretation of intravital microscopic observations is complicated by the "inflammatory"-type response to the trauma inflicted on the tissue by the surgical preparation. The present study evaluates different experimental conditions for prolonged observations of the mesenteric microcirculation in the rat. METHODS: The mesentery was exteriorized through a median laparotomy and subjected to an organ bath or a modified plastic foil technique. Hemodynamic, metabolic, respiratory, and microcirculatory data were analyzed. RESULTS: In contrast to the plastic foil technique, which yielded stable baseline values over a 5-h observation period, venular velocity and wall shear rates decreased significantly in the organ bath technique, and leukocyte adhesion to the endothelium was significantly increased. Likewise, abdominal blood flow decreased significantly by 35% and base excess declined (-10.0+/-0.4 mmol/L) in the organ bath, with reduced pco(2) (26.4+/-2.5 mm Hg vs. 33.7+/-1.1 mm Hg in plastic foil technique) due to respiratory pH compensation. CONCLUSIONS: The plastic foil technique was found clearly superior to the organ bath technique for maintenance of stable baseline metabolic, hemodynamic, and microcirculatory conditions in mesenteric intravital microscopy.

Animals↗

PubMed2000

Laser Doppler scanning: how many measurements are required to assess regional cerebral blood flow?

This study was initiated to determine the optimal number of measuring sites necessary to estimate regional cerebral blood flow (CBF) under pathophysiological conditions. 25 rats were exposed to 15 minutes of global cerebral ischemia. Local CBF was sequentially measured by laser Doppler (LD) at 32 locations during baseline conditions, ischemia and reperfusion using a computer-controlled scanning technique. A simulation study was performed based on 800 local measurements at each time point: random samples (size 1-100) were repeatedly drawn to estimate the variability of median flow. Accuracy was defined as probability that the simulated median differed less than +/- 5 LD-units from the true median of the 800 data. Above a single location, CBF was measured with an accuracy of 21.6 +/- 0.4% (baseline conditions, n = 100 simulations, mean +/- SEM), 85.8 +/- 0.4% (ischemia) and 11.1 +/- 0.3% (30th min. reperfusion). Accuracy increases to 75.2 +/- 0.5% (baseline conditions), 100 +/- 0% (ischemia) and 41.8 +/- 0.6% (30th min. reperfusion) if 24 locations are scanned. Scanning, therefore, improves accuracy and reduces variability of CBF measurements. With enough local CBF measurements laser Doppler assessment of regional CBF is possible. Single location CBF assessment is sufficiently accurate only during ischemia. During reperfusion, when accuracy is half reduced compared to baseline conditions, larger sample sizes are required.

Animals↗

PubMed2000

Spreading depression induces permanent cell swelling under penumbra conditions.

BACKGROUND: Spreading depression (SD) is known to go along with temporary breakdown of ion gradients and cell swelling which spontaneously normalizes. Here, the effects of SD at reduced flow conditions as encountered in the ischemic penumbra are examined. METHODS: In rats the right carotid artery was permanently occluded. MABP was lowered to 50 mmHg for 30 min. This is sufficient to reduce CBF to penumbra-like conditions in the right hemisphere. The following parameters were assessed: rCBF, DC potential, and tissue impedance. 5 or 15 min after onset of flow reduction one SD wave was initiated by microinjection of KCl. Histology was performed after 7 days. RESULTS: In animals with hypotension there was depolarization resembling anoxic depolarization after SD induction and an uncoupling of CBF and metabolism only in the right hemisphere. Impedance increased with SD but did not recover spontaneously as long as rCBF remained reduced. 15 min of SD-induced cell swelling was tolerated without permanent damage, whereas 25 min were followed by severe neuron loss in the affected cortex after 7 days. CONCLUSIONS: The study demonstrates the induction of penumbra conditions in the cortex of one hemisphere. SD is followed by cell swelling which persists as long as flow is critically reduced. The experiments illustrate how peri-infarct depolarizations may detrimentally affect the penumbra.

Animals↗