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Oliver Kempski

Publications and source records attributed to Oliver Kempski.

At least 19 recordsLinked to original sources
PubMed2007

C1-esterase inhibitor reverses functional consequences of superior mesenteric artery ischemia/reperfusion by limiting reperfusion injury and restoring microcirculatory perfusion.

Activated complement contributes significantly to reperfusion injury after ischemia. This study explores functional consequences of C1-esterase inhibitor (C1-INH) treatment after superior mesenteric artery occlusion (SMAO)/reperfusion using intravital microscopy. Thirty anesthetized, spontaneously breathing, male Sprague-Dawley rats underwent SMAO for 60 min followed by reperfusion (4 h). C1-esterase inhibitor (100 and 200 IU/kg body weight) or saline (0.9%) was given as a single bolus before reperfusion. Sham-operated animals (n = 10) without SMAO served as controls. Systemic hemodynamics were monitored continuously, arterial blood gases analyzed intermittently, and leukocyte/endothelial interactions in the mesenteric microcirculation quantified at intervals using intravital microscopy. Ileal lipid-binding protein (I-LBP) levels were determined from serum samples with an enzyme-linked immunosorbent assay at the end of the experiments. C1-esterase inhibitor restored microcirculatory perfusion to baseline levels in a dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1-INH treatment efficiently prevented metabolic acidosis, reduced the need for intravenous fluids to support blood pressure, and decreased I-LBP levels in a dose-dependent manner. Survival rates were 100% in controls and after 200 IU/kg C1-INH, 90% after 100 IU/kg C1-INH, and 30% in saline-treated animals. C1-esterase inhibitor bolus infusion efficiently blunted functional consequences of mesenteric ischemia/reperfusion with I-LBP, proving to be a valuable serum marker mirroring the effect of ischemia/reperfusion and treatment at the end of the experiments.

Animals↗
PubMed2006

Cerebral embolic ischemia in rats: correlation of stroke severity and functional deficit as important outcome parameter.

The embolic MCA occlusion model in rats is used for recanalisation studies in acute stroke. In addition to the determination of lesion size, the assessment of functional outcome may improve the value of this model. Male Wistar rats were submitted to MCA clot embolism or sham surgery. In order to achieve a larger variety of lesion volume, 2 subgroups (each 7 animals) were subjected to differently sized emboli (30 and 40 mm). Follow-up period was 6 days. Outcome assessment consisted of a test battery including parallel bar crossing, observation of behaviour in an open field and an 8-arm maze and a neurological score with ten different sensorimotor and coordinative items. Animals were perfusion-fixed on day 7 (blinded examination). For both subgroups, there were significant impairments with regard to performance on the Neuro score, parallel bar crossing and maze exploration. Improvement was only partial during the follow-up period. On follow-up day 6, there was still a significant correlation between total infarct volume and functional outcome on the Neuro score (R=0.80, p=0.0006) and the exploration behaviour in the maze (R=0.66, p=0.01). Application of emboli with a length of 40 mm caused more functional impairment and a more extended lesion volume compared with 30 mm. We present outcome tests that provide quantitative and objective tools to test functional impairment in rats following embolic stroke.

Analysis of Variance↗
PubMed2006

Anti-inflammatory treatment with standardized human serum protein solution reduces local and systemic inflammatory response after hemorrhagic shock.

OBJECTIVE: Reperfusion after hemorrhagic shock leads to local and systemic inflammatory response. This study evaluates the effect of a short-term treatment with standardized human serum protein solution (SPS) on the local and systemic inflammatory response in the mesenteric microcirculation in the rat. METHODS: Spontaneously breathing animals underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume-controlled hemorrhagic shock was set by arterial blood withdrawal (2.5 ml/100 g body weight for 60 min), followed by reperfusion for 4 h. SPS (n = 10) or saline 0.9% (controls, n = 10) was given intravenously as a continuous infusion for 30 min at the beginning of reperfusion ('pre-hospital'). This was followed in both groups by substitution of blood and normal saline to support blood pressure ('in-hospital'). Systemic hemodynamics, mesenteric microcirculation and arterial blood gases were monitored before, during and after shock, and for 4 h after initiation of reperfusion. RESULTS: SPS treatment markedly reduced leukocyte/endothelial interaction, and reduced the need for intravenous fluids compared to controls. For the entire observation period, blood pH was unchanged from baseline only in SPS-treated animals. The improvement of base excess and abdominal blood flow persisted for 2 h after SPS infusion. CONCLUSION: Short-term SPS treatment of hemorrhagic shock improved mesenteric microcirculation, arterial blood gases and global hemodynamics, and attenuated the inflammatory response to reperfusion. It may provide clinical benefit when applied at an early phase of reperfusion after hemorrhagic shock.

Animals↗
PubMed2006

Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats.

BACKGROUND AND PURPOSE: Ultrasound-accelerated thrombolysis is a promising approach toward acute stroke treatment. In previous in vitro studies, we demonstrated enhanced thrombus destruction induced by 20-kHz ultrasound. However, little is known about biological interactions of low-frequency ultrasound with brain tissue. The aim of this in vivo MRI study was to assess safety aspects of transcranial low-frequency ultrasound in rats. METHODS: The cranium of 33 male Wistar rats was sonificated for 20 minutes (20-kHz continuous wave). Power output was varied between 0 and 2.6 W/cm2. Tympanal and rectal temperature was monitored. Diffusion-weighted imaging and T2-weighted imaging was performed before and 4 hours, 24 hours, and 5 days after sonification. Apparent diffusion coefficients (ADCs) and T2 relaxation time (T2-RT) were measured in regions of interest in the cortex and the basal ganglia. The animals were euthanized for histological evaluation thereafter. RESULTS: Tympanal temperature increased significantly during insonation with 1.1 and 2.6 W/cm2. ADCs decreased significantly at 0.5 and 1.1 W/cm2, indicating cytotoxic edema. T2-RT increased significantly in the 0.5 and 1.1 W/cm2 group, consistent with vasogenic edema. No changes were detectable in the low-power output group (0.2 W/cm2). After sonification with 2.6 W/cm2, a significant loss of neurons could be detected on histopathology. Furthermore, 3 animals developed circumscript cortical lesions that could be identified as parenchymal necrosis. CONCLUSIONS: Low-frequency ultrasound caused vasogenic and cytotoxic brain edema and intracerebral necrosis in a dose-dependent fashion. This study indicates therapeutic low-frequency ultrasound as being potentially harmful and underlines the necessity of careful evaluation in further animal models.

Animals↗
PubMed2006

The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning).

BACKGROUND: Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. METHODS: Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. RESULTS: Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. CONCLUSIONS: Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

Animals↗
PubMed2006

An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia.

OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 +/- 0.7 vs. 85 +/- 1.4, mean +/- se), and almost blunted neuronal cell death (hippocampal CA1, 2150 +/- 191 vs. 884 +/- 141 neurons/mm; cortex, 1746 +/- 91 vs. 1060 +/- 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

Animals↗
PubMed2006

Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs.

INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

Acute Disease↗
PubMed2006

Local gingival blood flow at healthy and inflamed sites measured by laser Doppler flowmetry.

BACKGROUND: This investigation aimed to: 1) develop a method to obtain reproducible laser Doppler flow readings (LDFRs) at the gingiva of the maxillary front teeth; 2) evaluate regional gingival blood flow (GBF) in healthy gingiva by laser Doppler flowmetry; 3) compare hand-held LDFR (H-LDFR) with splint LDFR (S-LDFR); and 4) monitor changes in GBF in experimental gingivitis (EG) and chronic gingivitis (CG). METHODS: The LDFR, gingival index (GI), and plaque index (PI) were measured at 13 gingival sites (teeth #6 to #11) in 10 healthy volunteers (five males and five females), 23 to 34 years of age, over a period of 12.5 +/- 3.27 days employing a partial-mouth EG model and in 11 patients (three males and eight females), 20 to 63 years or age, with CG. LDFRs were obtained by S-LDFR or H-LDFR. RESULTS: H-LDFRs were significantly higher than S-LDFRs (P <0.05). All EG subjects developed gingivitis (PI: 2.77 +/- 0.23; GI: 1.5 +/- 0.53). EG-LDFRs at diseased sites increased slightly but not significantly over the study period. All CG-patients had high plaque and inflammation scores (PI: 2.8 +/- 0.2; GI: 1.63 +/- 0.78). CG-LDFRs at sites with GI >1 were significantly higher than LDFRs at healthy sites (P <0.05). CG-LDFRs were significantly higher than EG-LDFRs at sites with a comparable GI (P <0.05). CONCLUSIONS: LDFRs are positively correlated with the degree of gingival inflammation. GBF demonstrated significant differences in EG and CG. Modifications of the probe are needed to enhance its clinical applicability in clinical research of periodontal diseases.

Adult↗
PubMed2006

Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina.

Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore,the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0. I mg/kg or 5 mg/kg), aspirin (I mg/kg or 7 mg/kg) or LDC (0. I mg/kg clopidogrel and I mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min.CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, -48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg,-65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0. I mg/kg) plus aspirin (I mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (-70%, p<0.05 y. Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.

Acute Disease↗
PubMed2005

Ultrasound-induced blood clot dissolution without a thrombolytic drug is more effective with lower frequencies.

BACKGROUND AND PURPOSE: Therapeutic ultrasound as stand-alone therapy or in combination with rt-PA has proven to be an effective measure for recanalisation of acute vessel occlusion in different in vitro and in vivo studies. Uncertainty still exists concerning the optimal frequency and intensity with regard to the thrombolytic efficacy of ultrasound. The purpose of this study was a direct comparison of different ultrasound frequencies, when otherwise using identical measurement settings and parameters. METHODS: Ultrasound-induced dissolution of fresh human blood clots was studied in a flow system using low-frequency continuous wave ultrasound of 20, 40 and 60 kHz. After calibration of each ultrasound probe, blood clots were exposed to local time average intensities of either 0.12 or 0.2 W/cm2. Exposure time of the clots to ultrasound was 10 min, the number of treated clots in each experimental group was 12. RESULTS: As tested with 0.2 W/cm2, we found the most pronounced thrombolytic effect with the 20-kHz probe (weight loss of blood clots: 52.4%) and the 40-kHz probe (49.4%), as compared to the 60-kHz probe (21.4%) and the control group (18.5%). The difference between the 20- and 60-kHz probes was statistically significant (p < 0.001). The treatment effect was clearly intensity dependent with a less pronounced, but still significant treatment effect at 0.12 W/cm2 (24.5% at 20 kHz; p < 0.001 compared to 0.2 W/cm2; p = 0.045 compared to controls). CONCLUSIONS: These data show that therapeutic efficacy of ultrasound, in absence of a thrombolytic drug, is frequency and intensity dependent with best results at low frequencies. With continuous wave transmission, the benefit may be limited to the very low frequency range. The results are a basis for further evaluation in animal models.

Anticoagulants↗
PubMed2005

MitoKATP-channel opener protects against neuronal death in rat venous ischemia.

OBJECTIVE: Mitochondrial adenosine triphosphate-dependent potassium (mitoKATP) channels are present in the brain, and several reports have shown their neuroprotective, preconditioning effect against an ischemic insult. The role of mitoKATP channels in the penumbra area has not been studied thoroughly. In a model of venous ischemia, widespread penumbra-like low flow areas are created, which are susceptible to cortical spreading depression. Thus, we studied effects of mitoKATP channels on infarct size in this model. METHODS: Male Wistar rats were subjected to two-vein occlusion by photochemical thrombosis of two adjacent cortical veins combined with KCl-induced cortical spreading depression. The rats were assigned to four experimental groups pretreated intraventricularly 15 minutes before two-vein occlusion with 1) vehicle, 2) the mitoKATP channel opener diazoxide (2 mmol/L), 3) diazoxide (2 mmol/L) plus the selective mitoKATP channel blocker 5-hydroxydecanoate (5-HD; 100 mmol/L), or 4) 5-HD alone (100 mmol/L). Regional cerebral blood flow (laser Doppler scanning) and brain cell swelling (impedance) were monitored acutely. Infarct volume was assessed 7 days after ischemia. RESULTS: Pretreatment with diazoxide significantly reduced the infarct volume from 6.2 +/- 0.7 mm3 to 3.8 +/- 0.4 mm3, whereas regional cerebral blood flow in the vicinity of the two veins was comparable in both groups 70 minutes after two-vein occlusion. Effects of diazoxide were abolished by 5-HD, whereas 5-HD alone even increased infarct volume. CONCLUSION: These results suggest that the opening of mitoKATP channels plays a major role in brain protection under penumbra-like conditions, as shown in this venous occlusion model.

Analysis of Variance↗
PubMed2005

Prolonged recirculation is required to detect secondary metabolic and hemodynamic deterioration after superior mesenteric artery occlusion.

We evaluated late (4 hrs) effects of reperfusion on hemodynamics after 30 or 60 min occlusion of the superior mesenteric artery (SMA) in a rat model. Spontaneously breathing animals (n=30) underwent occlusion of the SMA for 0 (sham), 30 (SMAO_30) or 60 min (SMAO_60) followed by reperfusion with normal saline. Abdominal blood flow (ABF), SMA blood flow (SBF), arterial blood pressure and heart rate were recorded continuously. Systemic vascular resistance (SVR) and SMA vascular resistance (MVR) were calculated at baseline and after 240 min reperfusion (240R). All animals survived in SMAO_30 and sham, two died in SMAO_60 after 120R. ABF remained constant in all groups. SVR increased in SMAO_30 and sham and decreased in SMAO_60 at 240R. SBF was significantly lower after reperfusion in ischemia groups as compared to sham. After 120R, SBF had increased significantly in SMAO_60 versus SMAO_30. MVR increased significantly in SMAO_30 but not in SMAO_60 and sham at 240R. 60 minutes SMA occlusion revealed early hemodynamic changes of septic circulation with increased blood flow in the SMA, decreased SVR, and pseudo-normalization of MVR. Prolonged observation periods are required to detect these significant changes which are overlooked when only studying 120 minutes of reperfusion as usually done.

Abdomen↗
PubMed2004

Accuracy and stability of temperature probes for intracranial application.

Intracranial temperature measurement may play a pivotal role for prognosis and treatment of neurological and neurosurgical patients. For reliable clinical application, accurate temperature readings are therefore necessary. We present an independent in vitro study investigating the accuracy and stability of three temperature probes. Eight Neurovent-P Temp (RN), eight Licox temperature sensors (LT) and eight Neurotrend sensors (NT) were placed into a water bath. The temperature was increased in 3 degrees C increments from 30 to 42 degrees C before (accuracy test day 0) and after (accuracy test day 5) a long-term stability test run at 37 +/- 0.2 degrees C. The accuracy tests revealed deviations of <0.25, <0.2 and >0.4 degrees C for the RN, NT and LT probes, respectively, when compared to the reference measurement by a precision Pt100 temperature measuring instrument. All sensor types showed stable readings over the course of 120 h. The high variability of LT probes was due to a malfunctioning Licox monitor. Excluding these values reduced deviation below 0.21 degrees C the standard deviation at each temperature step was below +/-0.08 (RN, NT) and +/-0.12 (LT), laying within the range provided by the manufacturer (RN, NT: +/-0.1; LT: +/-0.2). In general, RN, NT and LT temperature measurement is reliable, but malfunctioning parts may lead to false interpretation of temperature readings. Therefore, validation of temperature probes to a reference temperature prior to clinical use is recommended.

Body Temperature↗
PubMed2004

Capillary flow and diameter changes during reperfusion after global cerebral ischemia studied by intravital video microscopy.

The reaction of cerebral capillaries to ischemia is unclear. Based on Hossmann's observation of postischemic "delayed hypoperfusion," we hypothesized that capillary flow is decreased during reperfusion because of increased precapillary flow resistance. To test this hypothesis, we measured cerebral capillary erythrocyte velocity and diameter changes by intravital microscopy in gerbils. A cranial window was prepared over the frontoparietal cortex in 26 gerbils anesthetized with halothane. The animals underwent either a sham operation or fifteen minutes of bilateral carotid artery occlusion causing global cerebral ischemia. Capillary flow velocities were measured by frame-to-frame tracking of fluorescein isothiocyanate labeled erythrocytes in 1800 capillaries after 1-hour reperfusion. Capillary flow velocities were decreased compared to control (0.25 +/- 0.27 mm/s vs. 0.76 +/- 0.45 mm/s; P<0.001). Precapillary arteriole diameters in reperfused animals were reduced to 76.3 +/- 6.9% compared to baseline (P<0.05). Capillary diameters in reperfused animals (2.87 +/- 0.97 microm) were reduced (P<0.001) compared to control (4.08 +/- 1.19 microm). Similar reductions of precapillary (24%) and capillary vessel diameters (30%) and absolute capillary flow heterogeneity indicate that delayed (capillary) hypoperfusion occurs as a consequence of increased precapillary arteriole tone during reperfusion.

Animals↗
PubMed2004

The hemodynamic effects of ephedrine on the onset time of rocuronium in pigs.

Several studies have found a correlation between the onset time of muscle relaxants, cardiac index, and muscle blood flow. Ephedrine increases these hemodynamic variables and shortens onset time of rocuronium in humans. Our aim in this animal study was to determine the effect of ephedrine on the onset time of rocuronium, cardiac index, and muscle blood flow after administration of thiopental. At predefined measuring points, mean arterial blood pressure and cardiac index were measured invasively and onset time was determined mechanomyographically. Twenty-four pigs were randomly assigned to three groups. Group I received etomidate and subsequently rocuronium (2 x 95% effective dose). Instead of etomidate, Group II received thiopental. In Group III, ephedrine 100 mug/kg was given before thiopental; additionally, muscle blood flow was measured (fluorescent microspheres). Although there were differences in hemodynamics between Groups I and II, this was not reflected in different onset times of rocuronium. In Group III, ephedrine compensated the thiopental-induced decrease of mean arterial blood pressure, cardiac index, and muscle blood flow, but no significant shortening of onset time (Group I: 74 +/- 21 s; Group II: 71 +/- 24; Group III: 69 +/- 22 s) was found. Our results demonstrated that ephedrine-related increases in cardiac index and blood flow did not shorten onset time of rocuronium in healthy pigs.

Androstanols↗
PubMed2003

Moderate controlled cortical contusion in pigs: effects on multi-parametric neuromonitoring and clinical relevance.

Over the last decade, routine neuromonitoring of ICP and CPP has been extended with new on-line techniques such as microdialysis, tissue oxygen (ptiO(2)), acid-base balance (ptiCO(2), pH) and CBF measurements, which so far have not lead to clear-cut therapy approaches in the neurointensive care unit. This is partially due to the complex pathophysiology following a wide-range of brain injuries, and the lack of suitable animal models allowing simultaneous, clinically relevant neuromonitoring under controlled conditions. Therefore, a controlled cortical impact (CCI) model in large animals (pig) has been developed. After placement of microdialysis, ptiO(2), temperature and ICP catheters, an unilateral CCI injury (2.6-2.8 m/sec velocity, 9 mm depth, 400 ms dwell time) was applied and neuromonitoring continued for 10 h. CCI caused a rapid drop in CPP, ptiO(2) and glucose, whereas ICP, glutamate and lactate increased significantly. Most parameters returned to baseline values within hours. Lactate stayed elevated significantly throughout the experiment, but the lactate-to-pyruvate ratio (LPR) changed only slightly, indicating no severely ischemic CBF. Contralateral parameters were not affected significantly. Evaluation of brain water content and histology (12 h post-CCI) showed ipsilateral brain swelling by 5% and massive cell damage underneath the injury site which correlated with changes of ICP, CPP, glutamate, lactate, and ptiO(2) within the first hours post-CCI. Moderate controlled cortical contusion in pigs induced a complex pattern of pathophysiological processes which led to 'early' histological damage. Thus, this new large animal model will enable us to investigate the effect of therapeutic interventions on multi-parametric neuromonitoring and histological outcome, and to translate the data into clinical practice.

Animals↗
PubMed2002

[The ultrasound contrast medium levovist increases the thrombolytic effect of low frequency ultrasound].

BACKGROUND: Therapeutic application of ultrasound is a promising tool to develop an alternative or additional treatment modality of acute vessel occlusion. It has previously been shown that ultrasound enhances the effect of pharmacologic thrombolytic agents and has a thrombolytic potential in "stand-alone" therapy. The purpose of this study was to determine, whether the presence of the echo contrast agent Levovist further increases the thrombolytic efficacy of ultrasound. MATERIAL AND METHODS: Thrombolytic efficacy of low-frequency (20.5 kHz) continuous-wave ultrasound was evaluated. Fresh human blood clots (age 3-6 h) were sonicated for 10 min at an intensity of 0.35 W/cm2. The thrombolytic effect of ultrasound alone and in combination with rt-PA (3 micrograms/ml) was assessed with and without addition of Levovist (2 mg/ml). Loss in weight of each blood clot was used to measure the extent of thrombolysis. The number of thrombi in each group was between ten and 18. Experiments were carried out in sodium phosphate buffer, at a temperature of 37 degrees C, in a flow system with a flow rate of 15 ml/min. RESULTS: The use of ultrasound alone showed a significant thrombolytic effect (41.8% weight loss), as compared to a control group (24.2%). The addition of Levovist further increased thrombolysis to 44.7%, which was not significant. However, in combination with rt-PA, ultrasound-mediated thrombolysis could be significantly increased from 65.8% to 74.2%, when Levovist was added (p < 0.05). CONCLUSION: These data show that the thrombolytic efficacy of low-frequency continuous-wave ultrasound in combination with rt-PA is augmented in the presence of Levovist.

Contrast Media↗