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Biomedical subjects

B Endrich

Publications and source records attributed to B Endrich.

At least 37 records · Page 2Linked to original sources

[Microvascular perfusion of malignant tumors--a therapeutic measure for enhancing the hyperthermia effect?].

Hypoxic regions of malignant tumors are poorly vascularized; they appear to be more susceptible to hyperthermia in vivo than tumor cells in vitro after an exposure to heat. In an attempt to explain this discrepancy, changes of microcirculatory flow in the tumor have been proposed as key mechanism for destroying adjacent tumor cells in particular. This study was conducted to define the impact of the microcirculation on tumor destruction after local hyperthermia. A transparent chamber was implanted in the dorsal skin fold and two permanent indwelling catheters placed in carotid artery and jugular vein of 45 Syrian golden hamsters. 48 h later, 4 X 10(4) cells of the amelanotic melanoma A-Mel-3 were implanted into the s.c. tissue covered by the chamber. 5 days later, at a tumor diameter of 3 mm, the microcirculation of this tumor was studied using intravital microscopy, a platinum multiwire electrode, television as well as micropuncture techniques for the determination of local PO2, microcirculatory blood flow and microvascular pressure. Measurements were taken at 30 degrees C and 15 min after reaching a tumor temperature of 35 degrees and 42.5 degrees C. When heating up the melanoma to 35 degrees C, an increase in capillary perfusion by 35% was noted. With an apparent maximum of capillary perfusion, there was no change in arteriolar pressure but a significant drop in venular pressure from 11.0 +/- 1.1 to 7.4 +/- 0.6 mmHg resulting in an increase of the arteriolo-venular pressure gradient while the systemic pressures were unchanged. At a tumor temperature of 42.5 degrees C, prestasis and stasis became apparent in capillaries and collecting venules. This was accompanied by a rise in capillary and venular pressure by 5 mmHg. At the same time, pronounced tissue hypoxia was present in the tumor with more than 50% of the values within the hypoxic range between 0 and 5 mmHg. Despite tissue hypoxia, the constriction of all tumor arterioles became evident 15-30 min after reaching a tumor temperature of 42.5 degrees C. The deterioration of tumor oxygenation was associated with damage of tumor cells such as swelling and destruction of mitochondria which was seen under the electron microscope. After 40 min at 42.5 degrees C, the attenuation of the endothelial lining around the entire vascular perimeter was seen in tumor capillaries.(ABSTRACT TRUNCATED AT 400 WORDS)

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Induced hypotension: action of sodium nitroprusside and nitroglycerin on the microcirculation. A micropuncture investigation.

Sodium nitroprusside (SNP)-induced hypotension is associated with tissue hypoxia in liver and skeletal muscle, suggesting a redistribution of nutritional capillary flow. To test this hypothesis, the effects of SNP and nitroglycerin (NTG) on striated muscle vessels were studied in 42 hamsters using intravital microscopy, quantitative video image analysis, a platinum multiwire electrode for local Po2 measurements, and a micropuncture system for the determination of microcirculatory pressure. A transparent chamber was implanted in a dorsal skin fold. When the mean arterial pressure was reduced to 70 or 40 mmHg by SNP, the precapillaries dilated and precapillary resistance decreased, but significant changes in venular diameter were not observed. However, SNP-induced hypotension was associated with a consistent increase in intravascular pressure within the venules. As a result, the arteriolar-venular pressure gradient was reduced by more than 50%. Furthermore, the functional capillary density was less, and tissue hypoxia was present during SNP hypotension. In contrast, NTG dilated both arterioles and venules in the microvascular network. Despite a lower blood cell velocity in all segments, the functional capillary density and local Po2 remained unchanged during NTG, principally because there was only a 10% reduction of the arteriolar-venular pressure gradient. These findings suggest that, in terms of tissue oxygenation, NTG may be preferable to SNP for deliberate hypotension.

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A novel method for follow-up studies of the microcirculation in non-malignant tissue implants.

Specimens of syngeneic spleen, myocardium, and spongious bone as well as lyophilized dura were implanted into a dorsal skinfold chamber of hamsters. Using intravital microscopy and quantitative video-image analysis, the formation of the implants microcirculation was observed for 2 weeks. The steps of revascularization were similar for spleen, myocardium, and spongiosa: After initial bleeding into the implants (12-54 h), the specimens cleared up and revealed small channels devoid of blood cells (diameter 2-5 microns) 3-4 days after implantation. After 3-5 days blood flow could be observed throughout the specimens. Despite these similarities, the evolving angioarchitecture was specific for each tissue. In contrast, dura specimens were not vascularized. Histology of the implants revealed characteristic structures of the original organs 10-15 days after implantation. It is concluded that the hamster dorsal skinfold chamber provides a suitable host tissue for syngeneic implants. By this procedure, the study of the microcirculation of remote or unpredictably moving organs becomes possible over prolonged periods of time.

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The fine structure of tumor blood vessels. I. Participation of non-endothelial cells in tumor angiogenesis.

This report provides fine structural evidence that, dependent upon the malignancy, tumor as well as mesenchymal cells may participate actively in the neovascularization of experimental tumors grown in transparent tissue chambers implanted into skinfolds of syrian hamsters. Such non-endothelial cells may help to promote angiogenesis in two different ways: (1) They are incorporated into capillary sprouts thereby accelerating the growth rate of the latter independent of endothelial cell proliferation. (2) Extravascular cells (tumor and mesenchymal elements) become integrated in varying numbers into the linings of comparatively large blood-perfused vessels. This facilitates the rapid establishment and functional remodelling of the microvascular bed to adapt the microcirculation to the varying local demands of the growing tumor. If these results can be confirmed for other tumors, and if they are independent of the tumor's environment and the experimental protocol, then we will have to reconsider the significance of tumor angiogenesis as a realistic biological model from which general conclusions with regard to neovascularization in non-tumorous tissues may be drawn.

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Capillary blood flow in the amelanotic melanoma of the hamster after isovolemic hemodilution.

In malignant tumors, spontaneous arteriolar vasomotion disappeared already during earliest tumor growth (tumor weight less than 200 mg) suggesting that arterioles supplying a malignant tumor with blood are maximally dilated from the very beginning of tumor growth. As a result, the viscosity of blood becomes a limiting factor of tissue perfusion. To evaluate the effects of isovolemic hemodilution in a malignant tumor, a transparent chamber model was used in conjunction with a subcutaneously growing amelanotic melanoma of the hamster. Quantitative intravital microscopy (video image analysis) and a platinum multiwire electrode were utilized to study the tumor microcirculation. Isovolemic hemodilution was performed by exchange of blood vs. Dextran 60 to lower the systemic hematocrit to 30% in 21 animals. Capillary flow increased significantly and improved tissue pO2 on the tumor's surface without any change in capillary density. Since tumor growth was accelerated after hemodilution, these data suggest to combine with hemodilution other treatment modalities to improve blood-mediated tumor therapy.

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[Effects of halothane and enflurane on the microcirculation].

The microcirculatory effects of halothane and enflurane were studied in a new experimental model before, during and after anaesthesia. It was only with complete volume substitution and a constant CVP during anaesthesia that blood cell velocity and capillary perfusion remained unchanged, whereas functional capillary density shifted the histogram of local pO2 to the right, i.e. towards increased pO2 values. Spontaneous arteriolar vasomotion was inhibited during anaesthesia with halothane and enflurane. The study also shows that homogeneous capillary perfusion and microcirculatory flow distribution during anaesthesia are closely related to normovolaemia and changes in CVP.

Anesthesia↗

Spontaneous arteriolar vasomotion as a determinant of peripheral vascular resistance.

Spontaneous changes of diameter in small arteries and arterioles were studied in the hamster skin fold chamber preparation, which allows to observe the microcirculation without acute exposure and anesthesia. Continuous measurements of diameter were made when the preparation appeared to be physiologically normal according to preset criteria. 89% of the arterial vessels studied showed spontaneous changes in diameter. The activity was prevalently periodic with 29% of the vessels exhibiting random changes in diameter. The amplitude of the periodic activity expressed as a percentage of the mean diameter increases in proportion to the vessel size, arterial vessels in the 40-100 micron diameter range exhibit amplitudes of the order of 10-20%. The smallest arterioles show changes as large as 100% of mean diameter, which cause these vessels to become temporarily occluded. This phenomenon is analyzed in terms of its effect on peripheral vascular resistance by means of an analytical model that assumes vasomotion to be a periodic phenomenon. It is shown that the presence of time dependent changes in vessels diameter similar to those observed, has an important effect on peripheral vascular resistance.

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Effects of prolonged cold injury on the subcutaneous microcirculation of the hamster. I. Technique, morphology and tissue oxygenation.

An animal model is described allowing for direct measurements of local tissue PO2, microhemodynamics and vascular density in the event of a prolonged non freezing cold injury. The model consists of implanting a transparent skin fold chamber in the dorsal skin fold in hamsters and of inserting two permanent indwelling catheters in jugular vein and carotid artery, respectively. The microcirculation was studied using a Wild Photomacroscope for photography and a platinum multiwire electrode for measurements of local PO2 in the conscious animal. After 72 h of recovery from anesthesia and surgery, the experimental was started with the animal immobilized. The decrease of local s.c. temperature was achieved by perfusing a heat exchanger with distilled H2O and Isopropanol 70% (1:1) at a rate of 81/min with the heat exchanger located directly beneath the aluminium frame of the chamber. With this technique, a decrease in local tissue temperature from 28 degrees C to 15 degrees C could be obtained within 15 min and was kept constant for 60 min. After photography of the microcirculation and local PO2-measurements, the local temperature was further reduced to 5 degrees C with 15 min. Sixty minutes later, the area exposed was slowly rewarmed from a level of 5 degrees C within 30 min. This procedure was repeated in intervals of 24 h over a period of five days. During the course of the experiments, local PO2 values shifted toward hypoxic or even anoxic values. Intravital microscopic observation revealed aggregate formation, stasis and obstruction of capillary flow associated with pronounced tissue anoxia after five cold exposures. This event resulted inevitably in tissue necrosis and scar formation after seven consecutive exposures to cold. It is concluded that this model can be used to study the effects of local non freezing cold injury in a precisely reproducible manner.

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Microcirculatory blood flow, capillary morphology and local oxygen pressure of the hamster amelanotic melanoma A-Mel-3.

Transparent chambers and permanent indwelling catheters were implanted in the dorsal skin flaps of 24 inbred golden Syrian hamsters. After 48 hours, 4 x 10(4) amelanotic melanoma cells (A-Mel-3) were transplanted sc (12 hamsters) in areas exposed for intravital microscopy. A platinum multiwire electrode and techniques for a quantitative analysis of television images were used for measurements of local oxygen pressure (PO2), capillary blood cell velocity, capillary density, and capillary diameter and length, whereas capillary morphology was evaluated by electron microscopy. Compared to the mean local PO2 of the skin flaps of controls (12 hamsters), the mean local PO2 on the tumor surface of melanoma-bearing hamsters decreased with tumor size. Although capillary density of the melanoma was elevated 4 days after tumor transplantation, it decreased significantly until day 12. Of hemodynamic significance were huge platelet conglomerates in short, dilated capillaries. Electron microscopy revealed endothelial hyperplasia, open endothelial junctions, and disintegration of the capillary endothelium. These findings strongly suggest that elevated microvascular resistance, intratumor tissue pressure, and widening of intercapillary distances in the melanoma might significantly diminish the impact of chemotherapeutic treatment.

Animals↗

[The effect of pentobarbital on the microcirculation of skeletal muscles and the subcutis. An animal-experimental study].

The effects of pentobarbitone anaesthesia on the macrohaemodynamics and the microvasculature of subcutaneous tissue and skin muscle were studied in hamsters (n = 14) utilizing intravital microscopy, quantitative video techniques and a platinum multiwire electrode for local PO2 measurements. After achieving anaesthesia with 35 mg/kg b.w. pentobarbitone, changes in macrohaemodynamic parameters, blood cell velocity and vessel diameters were not observed. However, after 30 min of pentobarbitone anaesthesia, 25% of the arteriolar blood volume coursed through arteriovenous shunts. The increase in a-v shunting was accompanied by a significant decrease of functional capillary density. As a result, local PO2 values decreased slightly after 30 min of pentobarbitone anaesthesia. These findings provide evidence that 35 mg/kg b.w. pentobarbitone cause alterations in capillary density and perfusion. It is concluded that with a dose of up to 35 mg/kg b.w. pentobarbitone, these changes have little effect on local tissue oxygenation.

Animals↗

Distribution of microflow and oxygen tension in hamster melanoma.

The present study was based upon the assumption that the efficacy of tumor treatment depends not only on the response of malignant cells to a given drug but on local oxygen tension as well as on number and alignment of capillaries. Transparent chambers were implanted in the dorsal skin flap of 32 Syrian (Gold) hamsters. Permanent indwelling catheters in carotid artery and jugular vein served for measuring the systemic pressures and heart rate; 48 hours later, 4 X 10(4) cells of the amelanotic melanoma A-Mel-3 were transplanted (16 animals) s.c. in the area exposed for daily intravital microscopy. A platinum multiwire electrode and quantitative video techniques were utilized for measurements of local PO2 and capillary blood flow. Capillary density, capillary diameter and surface area were analyzed throughout the vascularized melanoma during the first 12 days of growth. When compared to controls (16 animals) and tissue in the immediate neighborhood of the tumor, mean local PO2 on the tumor's surface decreased with tumor size. Capillary density of the melanoma was elevated 4 days after tumor inoculation but decreased significantly until day 12. As a result of enhanced capillary diameters, capillary surface area increased eight-fold during earliest growth of the melanoma. Of hemodynamic significance were huge platelet conglomerates consistently noted in short, dilated capillaries at the melanoma edge. As a consequence, the number of erythrocyte perfused capillaries decreased with tumor growth and 38% and 50% of the arterial inflow was bypassing the capillary network 8 and 12 days after tumor inoculation. These data indicate that due to rarefication of capillaries, the full impact of tumor treatment is diminished by an elevated microvascular resistance which could significantly affect the therapy of the melanoma. On the basis of these studies it is concluded that improvement of the blood's fluidity might result in a better response to adjuvant chemotherapy of the melanoma.

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[Changes in microcirculation by the administration of sodium nitroprusside and nitroglycerin].

The effects of hypotension induced by sodium nitroprusside (SNP) or nitroglycerin (NTG) were evaluated in hamsters (n = 12). No differences in macrohemodynamic parameters were found during and after hypotension with either drug tested. SNP dilated predominantly the precapillaries and NTG dilated all microvascular segments. Blood cell velocity decreased in both groups. A significant volume of blood was diverted through av-shunts during SNP hypotension of 40 mm Hg. Capillary density decreased significantly during and after SNP-induced hypotension, whereas capillary density remained unchanged when NTG was used. The data favour the use of NTG when hypotension is deliberately induced.

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