Search PubMed⌕ Search

Biomedical subjects

M M Gebhard

Publications and source records attributed to M M Gebhard.

At least 19 recordsLinked to original sources
PubMed2003

Monitoring of water content and water distribution in ischemic hearts.

We determined water content and water distribution by fitting dielectric spectra of ischemic canine hearts between 5 MHz and 3 GHz with a newly developed model which describes heart cells and subcellular organelles as rotational ellipsoids filled with electrolyte enclosed by an isolating membrane. The fraction of dry material is modelled by spherical particles with a small dielectric permittivity. Free model parameters were water content, cell volume fraction, and the conductivity of the electrolytes. Resulting model parameters were compared to data from tissue desiccation and to conductivity changes produced by protons and lactate ions. We investigated hearts in two states: during ischemia after interruption of blood flow (pure ischemia, PI, n=5) and during ischemia after resuscitation with Tyrode's solution (IAR, n=14). The difference between water content determined by tissue desiccation and by dielectric spectroscopy was less than 0.5%. During 360 min of ischemia, water content in IAR decreased from 85+/-1.6% to 83+/-2.2% and in PI from 80+/-0.8% to 78+/-1.5%. Cellular volume fraction in IAR increased from 0.47+/-0.045 to 0.63+/-0.031 and in PI from 0.62+/-0.014 to 0.73+/-0.013, which is consistent with published morphometric data. After 180 min of ischemia, the increase of the cytosolic conductivity was 0.14+/-0.02 S/m as calculated from the dielectric spectrum and was similar to the conductivity increase which was roughly estimated on the basis of tissue lactate concentration. In conclusion, dielectric spectroscopy combined with our model analysis facilitates the monitoring of water content and distribution by means of nondestructive surface probes.

Animals↗
PubMed2003

Characterization of hepatic parenchymous perfusion heterogeneity and regional flow kinetics after porcine liver transplantation.

BACKGROUND: In clinical practice, a heterogeneous hepatic tissue microperfusion (MC) is often observed after liver resection or transplantation (LTx). Nevertheless this hepatic perfusion phenomenon has never been really quantified with respect to its anatomic distribution and time course in detail. The aim of the study was to characterize liver perfusion heterogeneity and local flow kinetics both in the physiological situation and after standardized ischemia and reperfusion using an established model of porcine LTx. METHODS: Regional distribution of hepatic MC in healthy native porcine livers (control group; n = 8) was analyzed in comparison with data derived 60 min, 24 h, and 72 h after porcine LTx (transplantation group; n = 8 each subgroup; cold ischemia time: 5.7 +/- 1.2 h). MC was measured with implanted thermal diffusion electrodes (TD). Flow in hepatic artery and portal vein was continuously detected by ultrasonic probes. For standardization of measurement localizations, porcine liver lobes were divided anatomically into three horizontal layers (cranial, medial, caudal), defining 12 distinct hepatic measurement regions. RESULTS: In the control group, a homogenous liver MC with a mean flow of 81.6 +/- 13.9 ml/100 g/min was detected in all regions. After LTx, a marked MC heterogeneity was noted 60 min after reperfusion. MC rehomogenization was first documented within horizontal liver planes 24 h later. Comparison of MC between planes showed persisting heterogeneity with a significant intralober drop of mean MC in the cranio-caudal direction. Complete MC rehomogenization (both between horizontal and vertical liver planes) was detected 72 h after reperfusion. Still, an overall reduction of mean liver perfusion by about 15% was existent. CONCLUSIONS: A homogenous tissue perfusion was observed in healthy porcine livers. In contrast, marked heterogeneity of hepatic MC was detected after LTx. Heterogeneity presents as a very dynamic and temporary phenomenon. Early horizontal flow rehomogenization and reconstitution of normal blood flow, particularly primarily in the cranial liver layers, appear to be characteristic features during early flow reconstitution after postischemic reperfusion. Due to heterogeneity and time-dependent flow dynamics, measurement of MC volumes at single hepatic regions may not always allow a valid characterization of liver perfusion quality during the first 24 h after postischemic reperfusion.

Animals↗
PubMed2003

In vivo assessment of angioarchitecture and microcirculation in experimental liver cancer: a new model in rats.

The rising incidence of unresectable hepatocellular malignancies remains a therapeutic challenge. Little is known about the mechanisms of angiogenesis and immunological aspects of liver tumor vessels. The aim of this study was to investigate hepatic and tumor microcirculation and leukocyte-endothelium interaction by means of intravital microscopy in a rat model of hepatocellular carcinoma. Off-line analysis showed that the angioarchitecture as well as blood flow velocity in liver cancer is heterogeneous. The leukocyte-endothelium interaction is significantly reduced compared to normal liver tissue. The data suggest that the main mechanism is a reduced expression of adhesion molecules demonstrating an effective immune escape mechanism of this tumor. The model represents a useful experimental tool to explore angiogenesis inhibition or immunological therapeutic strategies in experimental liver cancer.

Animals↗
PubMed2003

Angiogenesis inhibition with TNP-470, 2-methoxyestradiol, and paclitaxel in experimental pancreatic carcinoma.

INTRODUCTION: Inhibition of tumor angiogenesis is a novel therapeutic modality for various malignancies. AIM: To investigate the effect of different antiangiogenic agents (TNP-470, 2-methoxyestradiol, and paclitaxel) on growth and neovascularization of experimental pancreatic cancer. METHODOLOGY: In 25 male Lewis rats, tumor induction was achieved by orthotopic and subcutaneous tumor fragment implantation of ductlike pancreatic cancer DSL6A. Four weeks after tumor implantation, the animals were randomly treated with TNP-470, 2-methoxyestradiol, or paclitaxel. After 2 weeks of antiangiogenic therapy, total tumor volume, vital tumor surface, vascular density, and apoptosis were measured. RESULTS: Total tumor volume and vital tumor surface were not significantly different in any of the treatment groups. Similarly, vascular density and apoptosis were not altered by treatment with the various angiogenesis inhibitors at the specific doses used. CONCLUSION: We conclude that in contrast to many earlier studies, angiogenesis inhibition by a single-drug application and by the doses used in the present model did not reveal a favorable therapeutic effect on pancreatic cancer DSL6A. The combination of different angiogenesis inhibitors or higher doses might be more effective.

2-Methoxyestradiol↗
PubMed2002

Experimental monitoring of hepatic glucose, lactate, and glutamate metabolism by microdialysis during surgical preparation of the liver hilus.

Mechanical liver manipulation can lead to hepatic microcirculation (MC) impairment. The pathobiochemical relevance of this phenomenon is not fully understood. Microdialysis (MD) allows a quantification of metabolic products in interstitial fluid, thus enabling analysis of the hepatic metabolic state during changes of liver perfusion. The aim of the study was to quantify the functional effects of standardized surgical liver preparation both on liver metabolism and microperfusion. Two groups of animals (pigs, n = 25) were formed: In the trial group (TG; n = 13) the liver was mobilized, followed by hilar preparation. In the control group (CG; n = 12) mobilization of the liver without hilar dissection was performed. Surgical manipulation was followed by an observation in both groups. Hepatic interstitial glucose, lactate, and glutamate concentrations were detected by MD and liver MC by thermodiffusion. During liver mobilization MC decreased significantly in both groups (TG; 86.7 +/- 2.0 to 73.4 +/- 2.3 ml/100 g min; and CG; 88.3 +/- 3.1 to 71.9 +/- 2.2 ml/100 g/min). In the trial group levels decreased further during hilar preparation reaching minimal values of 65.6 +/- 2.8. After preparation MC recovered to baseline. Glucose, lactate, and glutamate concentrations increased significantly during liver mobilization in the trial (glucose; 0.52 +/- 0.13 to 0.88 +/- 0.19 mmol/L; lactate; 0.34 +/- 0.07 to 0.54 +/- 0.07 mmol/L; glutamate; 34.5 +/- 3.6 to 52.6 +/- 8.0 micromol/L) and control group (glucose; 0.58 +/- 0.06 to 0.95 +/- 0.13 mmol/L; lactate; 0.30 +/- 0.06 to 0.49 +/- 0.07 mmol/L; glutamate; 32.9 +/- 2.36 to 56.1 +/- 5.12 micromol/L). Throughout hilus preparation maximum values could be measured in TG (glucose; 1.69 +/- 0.34; lactate; 0.90 +/- 0.18; glutamate; 63.5 +/- 7.2). After termination of mobilization or preparation baseline concentrations were reached again. MD allows monitoring of metabolic changes in hepatic parenchyma. Surgical liver preparation leads to changes of intrahepatic glucose, lactate, and glutamate levels (without alterations of parameters in systemic plasma) along with hepatic MC impairment. Reconstitution of hepatic MC was accompanied by rapid normalization of metabolic parameters. By measuring specific parameters, MD could prove to be of use for functional assessment of metabolic effects due to MC disturbances.

Animals↗
PubMed2002

The complex dielectric spectrum of heart tissue during ischemia.

INTRODUCTION: Because of the variety of tissue structures, the interpretation of the passive complex dielectric permittivity spectrum epsilon (omega) of the heart is still a problem. The aim of this work was to correlate epsilon (omega) of heart tissue with physical processes on cellular level. METHODS: epsilon (omega) of canine hearts was continuously measured in the range from 10 Hz to 400 MHz during cardioplegic perfusion and during following ischemia. Cardioplegic perfusion was performed with HTK (Custodiol) without or with heptanol, in order to produce electrical cell uncoupling via the closure of gap junctions. To analyse epsilon (omega), we present two heart models which consider cell shape, electrical cell coupling, and dielectric polarisation of cell membranes and membranes of intracellular structures. RESULTS: epsilon (omega) of heart tissue shows an alpha-, beta-, and gamma-dispersion. epsilon (omega) remains unchanged during cardioplegic perfusion with HTK, but if heptanol is added, there is an immediate decrease in the region of alpha-dispersion and an increase in the low frequency part of beta-dispersion. Similar changes are observed during ischemia following HTK perfusion without heptanol; additionally, the beta-dispersion shifts to higher frequencies. Using our models, we obtain analogue changes of epsilon (omega) by fitting model parameters which describe water content, water distribution, extra- and intracellular conductivity, and gap junction resistance. DISCUSSION: Changes of these tissue properties as calculated by our models based on the measurement of epsilon (omega) are consistent with intraischemic changes of heart tissue known from immunohistochemical, biochemical, and histological investigations. The next step will be to use our models for the prognosis of irreversible tissue damage.

Animals↗
PubMed2002

Glutathione depletion with L-buthionine-(S,R)-sulfoximine demonstrates deleterious effects in acute pancreatitis of the rat.

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.

Acute Disease↗
PubMed2002

The role of pre-ischaemic application of the nitric oxide donor spermine/nitric oxide complex in enhancing flap survival in a rat model.

Spermine/nitric oxide complex (Sper/NO) is a new nitric oxide (NO) donor with a long half-life providing controlled biological release of NO in vivo. The purpose of this study was to determine whether flap survival could be improved by pre-ischaemic or post-ischaemic intravenous administration of Sper/NO. We divided 37 male Wistar rats into four experimental groups. An extended epigastric adipocutaneous flap was raised in each animal. The mean area of flap necrosis was assessed for all groups on the fifth postoperative day, using planimetry software. The average area of flap necrosis was mean +/- s.d. = 68.2%+/-18.1% in the control group, and 29.7% +/- 13.3% in the non-ischaemic controls. The group with pre-ischaemic application of Sper/NO demonstrated an average flap necrosis of mean+/-s.d. = 11.2%+/-5.9%, whereas this increased to 59.2%+/-14.4% in the group receiving Sper/NO 5 min prior to reperfusion. The group with pre-ischaemic application of Sper/NO showed a significantly lower area of flap necrosis than either of the control groups or the group receiving Sper/NO just prior to reperfusion (P < 0.05). The group receiving Sper/NO just prior to reperfusion demonstrated a significantly higher mean area of flap necrosis than the non-ischaemic controls (P < 0.05), but did not differ significantly from the control group. Our data show that pharmacological preconditioning and enhancement of flap survival can be achieved by intravenous administration of Sper/NO. The application of Sper/NO at the end of the ischaemia period or in the early reperfusion period provides no protection against ischaemia-reperfusion injury.

Animals↗
PubMed2002

Dopexamine attenuates microvascular perfusion injury of the small bowel in pigs induced by extracorporeal circulation.

BACKGROUND: Cardio-thoracic surgery with the use of extracorporeal circulation may lead to an impairment of splanchnic perfusion. The aim of this study was to investigate the effect of dopexamine on gastrointestinal microvascular perfusion failure due to extracorporeal circulation. METHODS: Twenty landrace pigs served as laboratory animals. A loop of the terminal ileum was exteriorized for microscopic observation. In 13 animals a partial left-heart bypass (pLHB), with a non-pulsatile pump flow of approximately 50% of the cardiac output, was established for 2 h. Seven animals received a continuous i.v. infusion of 3 micrograms kg-1 min-1 dopexamine from the beginning of pLHB to the end of the experiment. Seven sham-operated animals served as controls. The microcirculatory network was analysed by means of intra-vital microscopy prior to, during pLHB, and 2 h after bypass. RESULTS: Despite normal haemodynamics measured by arterial pressure and cardiac output, pLHB led to significant impairment of microvascular perfusion characterized by arteriolar vasoconstriction, reduction of functional capillary density (FCD) to 30% 2 h after weaning off bypass and diminished blood-cell velocities in submucous venules. Dopexamine attenuated this perfusion impairment, preventing arteriolar vasoconstriction. FCD remained normal. CONCLUSION: Our data demonstrate that treatment with the vasoactive drug dopexamine leads to a significant reduction of the perfusion injury of the small bowel.

Adrenergic beta-Agonists↗
PubMed2001

Desmopressin impairs microcirculation in donor pancreas and early graft function after experimental pancreas transplantation.

BACKGROUND: Protective effects of desmopressin in brain dead organ donors oppose reports on a hypercoagulatory potential and an increased leukocyte-endothelial interaction (LEI) after application of the drug. The aim was to evaluate the effect of desmopressin on organ donor's pancreas and early graft function. METHODS: Donor microcirculation was evaluated via intra-vital microscopy (IVM) in 24 BR (di/di) rats with central diabetes insipidus, randomly assigned to groups I (control without desmopressin application), II (single i.v. application, no pretreatment) or group III (single i.v. desmopressin application, s.c. pretreatment for 3 days). Microcirculation in recipients was evaluated 1 hr and 6 hr after syngenic pancreas transplantation. Groups III and I served as organ donors. After IVM specimens were taken for histology and immunohistochemistry. RESULTS: Desmopressin in II vs. I led to temporarily (30') increased LEI (Sticker 274.3+/-87.7 vs. 76.5+/-31.1/mm2 endothelial surface; P<0.01) and impaired microcirculation (MCEV 0.43+/-0.07 vs. 0.99+/-0.06 mm/s; P<0.01). Repeated application reduced MCEV and increased LEI for up to 12 hr. Histology in I vs. III showed increased inflammation (n.s.), necrosis (P<0.05) and vacuolization (P<0.01). Immunohistochemistry revealed increased endothelial P-selectin 20' after application. 6 hr after reperfusion organs from III showed reduced MCEV and increased LEI (P<0.01). CONCLUSION: Repeated application of desmopressin impairs graft microcirculation. Perfusion of the pancreas is significantly reduced at the beginning of organ tissue conservation as well as after reperfusion. These disturbances might partly be due to observed endothelial P-selectin expression. Application of desmopressin up to 12 hr prior to organ explantation may impact graft quality.

Animals↗
PubMed2001

Differential value of adenosine myocardial contrast echocardiography and dobutamine stress echocardiography in evaluating functional significance of coronary artery stenosis in a porcine model.

AIM: Myocardial contrast echocardiography (MCE) during adenosine induced hyperemia is an experimental method that detects flow limiting coronary artery stenosis by visualizing myocardial perfusion defects. Noninvasive detection of flow limiting coronary artery stenosis in clinical routine is a frequent domaine of dobutamine stress echocardiography (DSE) visualizing ischemia related regional wall motion abnormalities. This study investigated the values of adenosine MCE and DSE in the detection of functionally significant coronary artery stenosis in an experimental open chest pig model. METHODS: A total of 28 proximal LAD stenoses were instrumented in 12 animals. Reduction of coronary blood flow reserve (delta CFR [%] ) was calculated as a marker of functional significance of coronary artery stenosis (mild to moderate stenosis: delta CFR < or = 50%; severe stenosis: delta CFR > 50%). Fractional area shortening (FAS) and wall thickening (WT) were calculated to evaluate regional wall motion. Peak myocardial contrast intensities (PCI) were measured following aortic root injections of Levovist' to detect mocardial perfusion defects. RESULTS: As a group, severe stenosis significantly reduced wall motion response to dobutamine (delta FAS: 12.0 +/- 3.0%, vs. 20 +/- 3.0% without stenosis, p < 0.05; delta WT: 2.2 +/- 0.9 mm vs. 0.0 +/- 0.8 mm without stenosis, p < 0.05) and diminished myocardial opacification during hyperemia (PCI: 59 +/- 8 units vs. 143 +/- 16 units without stenosis, p < 0.05). Mild to moderate stenosis did not influence wall motion but reduced myocardial opacification (PCI 89 +/- 14 units vs. 143 +/- 16 units). PCI correlated more closely with alterations in CFR (r = -0.7, p < 0.0001) than did FAS (r = -0.5, p < 0.002) or WT (r = -0.2, p = 0.3). CONCLUSION: Adenosine myocardial contrast echocardiography detects flow limiting coronary artery stenosis and compares favorably to regional wall motion analysis during dobutamine infusion.

Adenosine↗
PubMed2001

Influence of steroids on microvascular perfusion injury of the bowel induced by extracorporeal circulation.

BACKGROUND: Extracorporeal circulation is associated with gastrointestinal complications. By means of intravital microscopic methods, we investigated whether preoperative treatment with steroids can attenuate the impairment of the bowel microcirculation. METHODS: In 20 pigs, a partial left heart bypass (pLHB) was established. A loop of the terminal ileum was exteriorized for intravital-microscopic observation. Seven sham-operated animals served as controls. In 13 animals, pLHB was established for 2 hours with a flow rate of 2,000 mL per minute; 7 of the animals received 20 mg/kg body weight prednisolone preoperatively. The microcirculatory network was analyzed before, during pLHB, and 2 hours after bypass. RESULTS: Despite unchanged macro-hemodynamics, pLHB resulted in a significant microvascular perfusion injury of the small bowel. Arteriolar vasoconstriction and a reduction of perfused capillaries per unit area (functional capillary density) to 30% of prebypass values could be found. Blood cell velocities were reduced in submucuous collecting venules. In the steroid-treated animals, the functional capillary density remained normal. In addition, arteriolar vasoconstriction could be prevented. CONCLUSIONS: Treatment with prednisolone largely prevents the microcirculatory alterations in the small bowel induced by extracorporeal circulation.

Animals↗
PubMed2001

Methysergide attenuates leukocyte-independent plasma extravasation during endotoxemia.

PURPOSE: During endotoxemia, the early endothelial damage has been shown to be leukocyte independent. Therefore, it was the aim of our study to investigate the role of serotonin in mediating leukocyte-independent microvascular permeability during endotoxemia. Microvascular permeability was determined after inhibition of the L-selectin mediated leukocyte adherence by fucoidin and after inhibition of serotonin effects by the serotonin (5HT)-receptor antagonist methysergide. MATERIALS AND METHODS: In male Wistar rats, leukocyte rolling, leukocyte adherence, and macromolecular leakage were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the serotonin-receptor antagonist methysergide, animals in the FUCO/ETX/5HT-ANT group received a continuous infusion of endotoxin. Animals in the FUCO/ETX group underwent the same procedure but received saline 0.9% instead of methysergide. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the saline group received volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to saline group. In the FUCO/ETX group, macromolecular leakage increased significantly, starting at 60 minutes. Values in the saline group increased slightly, being significant at 120 minutes, whereas vascular permeability remained unchanged in the FUCO/ETX/5HT-ANT group. Differences in macromolecular leakage between the FUCO/ETX-group versus the FUCO/ETX/5HT-ANT group and the saline group were significant at 120 minutes. Differences in macromolecular leakage between the FUCO/ETX/5HT-ANT group and the saline group were not significant. CONCLUSIONS: The leukocyte-independent endothelial damage during early endotoxemia can be inhibited efficiently by the 5-HT-receptor antagonist methysergide, indicating that serotonin plays an important role in that pathophysiology.

Animals↗
PubMed2001

Hirudin protects from leukocyte/endothelial cell interaction induced by extracorporeal circulation.

BACKGROUND: The clinical complications of Extracorporeal Circulation (ECC) have been linked to disturbances in the microcirculation. In order to prevent these deleterious effects, a biodegradeable agent to coat the extracorporeal circuit was tested. METHODS: Intravital fluorescence microscopy was used on the hamster skinfold chamber model in permanently instrumented, awake animals. ECC was introduced via a micro-roller-pump and a silicon tube shunted between the carotid artery and the jugular vein. The ECC-tube system was coated with PEG-Hirudin-Iloprost, two additional groups received either Iloprost i.v. (0.8 mg/kg/h) or Hirudin i.v. (1 mg/kg b.w.). RESULTS: ECC for 20 minutes resulted in an increase in rolling and adherent leukocytes in postcapillary venules (Roller 9 to 36 [%]; Sticker 24 to 330 [n/mm2]). Use of the coated tube system reduced L/E cell interaction (Roller 9 to 24* [%], Sticker 28 to 194* [n/mm2]; *p<0.05), whereas Hirudin i.v. nearly abolished it. CONCLUSIONS: The protective effects of the coating and of Hirudin i.v are probably a result of an attenuated activation of the coagulation-fibrinolytic system.

Animals↗
PubMed2001

Online detection of myocardial ischemia by near infrared spectroscopy with a fiberoptic catheter.

BACKGROUND: The interruption of myocardial O2-supply in acute myocardial ischemia causes differences in coronary venous O2-content. In this study, the oxygenation status of coronary sinus blood is detected in myocardial ischemia by near infrared (NIR) spectroscopy. METHOD: For the intravascular application, a new fiberoptic catheter is developed. After calibration of the catheter by perfusion of blood with standardized gas mixtures in an in vitro experiment, the in vivo application was performed in 12 domestic pigs. The catheter was placed into coronary sinus and an anterior ischemia was induced by temporary occlusion of LAD. NIR graphs and hemodynamic data were obtained for 90 min ischemia and 90 min reperfusion time. RESULTS: Main NIR-spectroscopic differences between oxygenated and de-oxygenated hemoglobin took place in O2-concentrations less than 30%. Coronary sinus NIR spectra of hemoglobin-oxygen binding showed significant, reproducible differences between pre-ischemia, LAD-occlusion and reperfusion. NIR graphs also show variations related to CO2-concentration, pH and temperature. CONCLUSION: The intravascular application of NIR spectroscopy could be a reliable tool in detection and follow-up of acute myocardial ischemia and infarction.

Animals↗