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K Messmer

Publications and source records attributed to K Messmer.

At least 343 records · Page 19Linked to original sources

Quantitative analysis of neovascularization of different PTFE-implants.

The process of neovascularization was analyzed in vivo in different expanded polytetrafluoroethylene (e-PTFE) implants which are frequently used in cardio-thoracic and vascular surgery. We have used the model of the hamster dorsal skinfold chamber which allows quantitative analysis of the microcirculation by means of intravital fluorescence microscopy. Pieces of approximately 1 mm2 of the cardiovascular patch (CVP, fibril length: 30 microns; n = 21), surgical membrane (SM, fibril length: 1 micron; n = 16), and soft tissue patch (STP, fibril length: 22 microns; n = 12) were implanted into the skinfold chambers. On day 10 after implantation, the functional density of newly formed microvessels was significantly (P less than 0.05) higher in CVP (145.0 +/- 10.9 cm-1) as compared to SM (688 +/- 13.9 cm-1) and STP (86.9 +/- 21.2 cm-1). In addition, CVP revealed a larger zone of neovascularization (311.6 +/- 19.4 microns) and the tightest integration (dynamic breaking strength: 17.9 +/- 3.0 cN/mm2) into the perigraft tissue, while SM demonstrated only few microvessels and no integration (6.0 +/- 1.9 cN/mm2) into the perigraft. None of the three different PTFE-implants revealed transmural ingrowth of capillaries. The internodal distance of PTFE implants seems to be the most important factor for neovascularization. Surgical membrane used for the replacement of passive biological membranes demonstrated, as is its purpose, little neovascularization and no integration into the perigraft tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neovascularization of prosthetic vascular grafts. Quantitative analysis of angiogenesis and microhemodynamics by means of intravital microscopy.

Neovascularization of prosthetic vascular grafts seems to play an important role in the prevention of early graft failure due to infection of thrombotic occlusion. The process of angiogenesis and neovascularization was analyzed for three different prosthetic vascular grafts (PTFE, Dacron double microvelour and gelatin-coated Dacron double microvelour) in vivo by means of fluorescence microscopy. Under Nembutal anesthesia (50 mg/kg BW) Syrian golden hamsters were fitted with a dorsal skinfold chamber, which contains the cutaneous skeletal muscle as well as subcutaneous tissue, and allows for quantitative analysis of the microcirculation for a prolonged period of time. In each chamber one piece (1mm2) of all three vascular grafts was implanted. Five days after implantation neovascularization was ascertained in 9/11 (coated) and 8/11 (non-coated) Dacron grafts, while only 4/11 PTFE implants revealed new microvessels. On day 10 the density of newly-formed microvessels was significantly higher (p less than 0.001) in Dacron grafts (234.3 +/- 31.2 cm-1 and 238.9 +/- 41.3 cm-1 respectively) as compared to PTFE implants (154.9 +/- 30.4 cm-1). In addition, Dacron grafts revealed a larger neovascularization zone extending into the perigraft tissue. 12 days after implantation non-coated Dacron grafts were most tightly integrated into the perigraft tissue. The better neovascularization of Dacron might be due to the high porosity of the graft compared to low porous PTFE, which revealed insufficient neovascularization.

Animals↗

Acute pulmonary microembolism induces different regional changes in preload and contraction pattern in canine right ventricle.

STUDY OBJECTIVE: The aim of the study was to investigate the influence of acute pulmonary embolism on local myocardial preload and contraction pattern in right ventricle. DESIGN: Measurements of preload and contraction pattern were made in inflow and outflow tracts of canine right ventricular free wall by sonomicrometry. Local right ventricular preload was assessed from end diastolic segment length. Contraction pattern was assessed from pressure-length loops and quantified by calculating maximal, systolic, and postsystolic shortening, and protosystolic segment elongation. Data were obtained before and after microembolization with 100 microns glass beads in combination with oleic acid. SUBJECTS: 13 foxhounds of either sex were used, weight 20.4 +/- 4.0 kg. MEASUREMENTS AND MAIN RESULTS: Pulmonary microembolization resulted in a rise in systolic, mean, and end diastolic right ventricular pressure and pulmonary vascular resistance. At the same time, the pressure-length loops, originally triangular or oval, became rectangular in both inflow and outflow tract. Normalised end diastolic segment length increased in the inflow tract from 10.0 to 10.3 mm (p less than 0.01), but simultaneously decreased in the outflow tract, from 10.0 to 9.6 mm (p less than 0.05). Segment shortening in the inflow tract was not affected but deteriorated in the outflow tract from 11.6 to 2.7% (p less than 0.01). CONCLUSIONS: Increase in afterload due to pulmonary microembolization caused regionally different changes in local preload and segment shortening in right ventricular free wall. Clinically available measures of global right ventricular preload do not assess these local differences in preload and therefore may fail to reflect the functional state of the right ventricle accurately.

Animals↗

Local and global function of the right ventricle in a canine model of pulmonary microembolism and oleic acid edema: influence of ventilation with PEEP.

Right ventricular (RV) dysfunction may occur due to increased RV afterload and, hence, might also contribute to the decrease in cardiac output following institution of PEEP in patients with adult respiratory distress syndrome (ARDS). To test this hypothesis, the authors examined the influence of PEEP on local and global RV function in 12 anesthetized dogs with experimental ARDS (eARDS) induced by pulmonary microembolization with glass beads and oleic acid. Local RV function was analyzed in the RV inflow tract (RVIT) and RV outflow tract (RVOT) by assessing both diastolic segment length, systolic segment shortening, and segment work (sonomicrometry). Global RV contractility was quantified by measuring maximum rate of pressure rise (dRVP/dtmax) and maximum velocity of contractile element shortening (Vmax). In eARDS, despite a fivefold increase in pulmonary vascular resistance, there was no change in cardiac index (CI), global RV contractility, RVIT and RVOT work, and RVIT shortening, whereas RVOT shortening decreased from 12.4 to 7.4% (P less than 0.01). Diastolic segment length increased in RVIT (P less than 0.05) but not in RVOT. PEEP of 10 cmH2O did not alter global RV contractility, RVIT and RVOT shortening, and RVIT work but reduced RVOT work (-35%; P less than 0.01) and CI (-11%; P less than 0.001). Cardiac index further decreased during PEEP of 20 cmH2O (-38%; P less than 0.001), while global RV contractility remained intact despite decreased RVIT and RVOT shortening (-32% and -69%; P less than 0.05) and work (-26% and -59%; P less than 0.01) in the presence of reduced fiber preload in both regions. From these findings, it was concluded that 1) the decreased CI during mechanical ventilation with PEEP at constant right ventricular end-diastolic pressure (RVEDP) is not caused by depressed global RV contractility in dogs with eARDS and a normal myocardium prior to insult. Decreased diastolic segment length and segment shortening during PEEP suggest that 2) PEEP reduces stroke volume by the Starling mechanism rather than by ischemia of the RV free wall. Finally, regionally incongruent changes of fiber preload indicate that 3) local differences in RV wall compliance are likely to occur subsequent to eARDS and PEEP.

Animals↗

Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis.

Dextran of different molecular weight (Dx 40, Dx 60/70) has often been evaluated as adjunct treatment of experimental acute pancreatitis. A beneficial effect has been documented by a decrease in its lethality. However, the mechanism of action is poorly understood. A specific effect on the pancreatic microcirculation generally has not been documented and differentiation from unspecific improvement of pancreatic blood flow due to volume expansion has been difficult. This investigation was designed to quantify the effect of dextran on the impairment of pancreatic microcirculation during acute biliary pancreatitis by means of intravital microscopy. Dextran 60 (Dx 60, molecular weight 60,000) was chosen in light of the increase in vascular permeability in the early stage of pancreatitis as demonstrated previously in the same model. Isovolemic hemodilution, i.e., exchange of whole blood for Dx 60 was used as a mode of administration to achieve instantaneous onset of therapy without changes in intravascular volume. In the control group a progressive reduction of pancreatic capillary perfusion commenced 30 minutes after induction of acute pancreatitis, resulting in cessation of nutritive tissue perfusion after 3 hours. In the animals subjected to hemodilution, stabilization of the pancreatic microcirculation was accomplished throughout the observation period of 6 hours. Because volume-related effects could be excluded by the protocol and by monitoring central venous pressure and hematocrit, a specific effect of hemodilution with DX 60 on the pancreatic microcirculation is indicated by our results.

Acute Disease↗

Direct monitoring of capillary perfusion following normovolemic hemodilution in an experimental skin-flap model.

The effects of normovolemic hemodilution on skin flap survival are studied in a recently developed skin-flap model (homozygous hairless mouse ear) in which nutritional capillary flow is monitored directly by means of intravital microscopy from the time of flap creation throughout the establishment of necrosis. Two diluting agents (dextran 60 and hydroxyethyl starch 200) are utilized. Our quantitative findings demonstrate that the amount of nonperfused tissue following flap creation in both the dextran (n = 23) and starch (n = 13) groups was significantly decreased as compared with controls (n = 19). Our qualitative observations suggest that improved hemorrheologic properties at the microcirculatory level are responsible for the observed decreased necrosis. Various mechanisms by which hemodilution may act to prevent necrosis are discussed.

Animals↗

Erythropoietin accelerates the recovery from extreme hemodilution: a randomized, placebo-controlled study in dogs.

Six splenectomized beagles of either sex (13.8 +/- 2.2 kg) were randomly treated either with 500 U/kg recombinant human erythropoietin (rhu-EPO) (verum group, n = 3) or an equivalent volume of the vehicle (placebo group, n = 3). Both solutions were given intravenously for 3 days. At day 4 after onset of treatment, the dogs were anesthetized and subjected to isovolemic hemodilution using 6% Dextran 60 (MW 60,000) down to a hematocrit of 0.10. During the recovery period vehicle or rhu-EPO was given every other day until the hematocrit reached control values. Every day venous blood samples were withdrawn, and the hematocrit as well as the concentrations of hemoglobin and 2,3-diphosphoglycerate were determined. In addition, the platelets and reticulocytes were counted. Treatment with rhu-EPO shortened the time of hematocrit recovery from 20 (placebo) to 11 days (p less than 0.05). The reticulocyte count peaked at day 2 (verum) versus day 5 (placebo). These findings indicate a successful stimulation of red blood cell production after extreme hemodilution in animals treated with erythropoietin. Therefore, rhu-EPO may allow to optimize blood donation programs as well as preoperative hemodilution and yield both, higher amounts of autologous blood and an accelerated reversal of dilutional anemia.

Animals↗

Blood rheology and systemic oxygen transport.

The interrelationship between systemic oxygen transport and hematocrit, has been studied under various conditions, while the influence of plasma viscosity on oxygen transport and tissue oxygenation has not entirely been explored. In experiments in dogs the plasma viscosity was increased either by isovolemic hemodilution with 6% hydroxyethyl starch (HES) 200/0.62, or 6% dextran-70, or by infusion of dextran-500 in a volume equivalent to 4% of blood volume from baseline to 3 mPa.s. Cardiac output and regional blood flow were assessed by means of radioactive labelled microspheres and local tissue oxygenation by means of pO2 multiwire surface electrodes. In normotensive healthy animals elevated plasma viscosity did neither jeopardize systemic nor regional blood flow; local tissue oxygenation of skeletal muscle remained unchanged or was even improved. We conclude that among the rheological factors influencing oxygen transport, the hematocrit plays the predominant role, while plasma viscosity is of minor importance.

Animals↗

Hyperosmotic saline dextran for resuscitation from traumatic-hemorrhagic hypotension: effect on regional blood flow.

The macro- and microcirculatory effect of small-volume resuscitation with hyperosmotic-hyperoncotic solutions was analyzed in 21 anesthetized beagles subjected to standardized traumatic-hemorrhagic hypotension (laparotomy and exteriorization of the intestine; MAP 40 mmHg for 75 min). Primary resuscitation consisted of bolus infusion of 10% of the blood loss (approx. 4 ml/kg) of either hyperosmotic (7.2%) saline -HSS-, hyperoncotic (10%) dextran 60 -HDS-, or hyperosomotic-hyperoncotic saline dextran (10% dextran 60 in 7.2% saline; HHS). Within 5 min CO was restored and systemic pressure significantly increased. In the HHS-group nutritional blood flow (RBF, measured by radiolabeled microspheres phi 15 microns) in kidneys, gastric mucosa, small intestine, colon, and pancreas was completely restored, while RBF to the myocardium, brain, and skeletal muscles exceeded baseline values. Despite the identical response in central hemodynamics, RBF to gastric mucosa, intestine, pancreas, and kidneys was significantly lower in HSS-animals (P less than 0.05 vs. HHS). In contrast, in the HDS-group CO, splanchnic, myocardial, and renal blood flow remained significantly reduced (P less than 0.05 vs. HHS). Despite the normalization of cardiac output by small volumes of hypertonic solutions, 7.2% saline alone failed to fully restore RBF after protracted traumatic hemorrhage. For the concept of small-volume resuscitation, the hyperosomotic-hyperoncotic solution of 10% dextran 60 in 7.2% saline appears to be most effective to improve organ perfusion during the prehospital period of trauma patients.

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[The importance of animal research for experimental surgery].

Animal experiments in biomedical research are ethically indispensable to minimize risks and to objectify superiority of diagnostic and therapeutic procedures. Innovative models allow understanding of complex systems and to formulate new hypotheses, however due to inherent limits cannot replace animal research. The high degree of complexity required for surgical experiments can often be achieved in small animals and allows to save domestic animals. Further expansion of biomedical research will not be associated with a greater number of animal studies.

Animal Welfare↗

A novel technique for studies on the microvasculature of transplanted islets of Langerhans in vivo.

Transplantation of isolated islets of Langerhans in diabetic patients is frequently followed by an early loss of function due to acute rejection. Since the primary target of host-vs-graft reaction is the endothelium of the microvessels, it is of great importance to analyze the microcirculation of freely grafted pancreatic islets. For this purpose we present a new model, allowing for intravital microscopy of the microvasculature of transplanted islets of Langerhans. The islets are isolated from Syrian golden hamsters and DA-rats, respectively, by a modified collagenase digestion technique. Subsequently, the islets are transplanted into a hamster dorsal skinfold chamber. Using intravital fluorescence microscopy and video techniques, the microcirculation of the islet grafts can be observed repeatedly over a time period of up to four weeks. Quantitative analysis of the microhemodynamics, i.e. functional capillary density, capillary RBC-velocity and microvascular diameters, can be performed by means of a computer assisted image analysis system. In addition, the model allows for investigation of the flow behaviour of white blood cells and their interaction with the endothelium of the microvascular segments. For the first time a model is presented, enabling for in vivo analysis of the revascularization process and microcirculatory function of transplanted islets of Langerhans. Furthermore, the model allows to assess microvascular phenomena during host-vs-graft reaction as well as effects of immunosuppressive regimens.

Animals↗

Microcirculation of the pancreas. A quantitative study of physiology and changes in pancreatitis.

A rabbit model was designed to study the microcirculation of the pancreas with special reference to changes occurring during acute pancreatitis. Intravital microscopy was used in conjunction with video techniques allowing for continuous observation and off-line evaluation of microvessel diameters and blood cell velocities. Based on the microvessel geometry a functional microvascular unit could be defined at the level of the pancreatic lobule consisting of intralobular arteries and veins and an arcade-like preferential pathway framing the capillary network. Experimental acute pancreatitis resulted in immediate leakage of the macromolecular plasma marker (FITC-Dextran 70) from the microvasculature suggesting increased permeability. In contrast to control conditions, pancreatic capillaries were excluded from the circulation during acute pancreatitis starting 30 min after induction with only single capillaries remaining perfused after 3 hours. At the same time, there was constant blood flow through the preferential pathways representing shunt perfusion.

Acute Disease↗