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Biomedical subjects

K Messmer

Publications and source records attributed to K Messmer.

At least 397 records · Page 22Linked to original sources

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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[Effect of the vasoactive drug buflomedil in arterial occlusive disease].

Peripheral occlusive disease is characterized by impairment of microcirculatory function in poststenotic vascular segments, independently from etiology and stage of the disease. The microcirculatory disorder results in impairment of the rheologic properties of blood, stagnation and maldistribution of nutritional flow; as a consequence local hypoxia and tissue acidosis will occur. Treatment of arterial occlusive disease in patients not amenable to surgery, therefore has to abolish the microcirculatory disorder. The vasoactive drug Buflomedil is well tolerated when administered at recommended dose and free from effects on the central hemodynamics. However, Buflomedil improves microvascular perfusion and function. This beneficial effect is the composite outcome of the drugs effect on red cell flexibility, platelet aggregation, oxygen need and redistribution of microvascular blood flow.

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The influence of PEEP ventilation on organ blood flow and peripheral oxygen delivery.

In an experimental study including 10 dogs with intact lungs (group I) and 10 dogs with oleic acid-induced pulmonary edema (group II), the effects of PEEP 10 and 20 (cm H20) on central hemodynamics, lung function, organ blood flow and tissue PO2 (liver and skeletal muscle) were examined. In both groups, PEEP resulted in a significant fall of cardiac output (CO) despite volume substitution. In group I, flow was redistributed favouring brain, heart, kidneys, and adrenals, at the expense of stomach, pancreas and and thyroid gland. Animals with pulmonary edema and consequently lower absolute values of CO showed a more uniform reduction of organ perfusion sparing only brain and heart PEEP 10 led to a marginal improvement of tissue oxygenation, whereas PEEP 20 resulted in a deterioration of local PO2 associated with a decrease in O2 transport. It is concluded that whenever PEEP is applied, a reduction and redistribution of CO may occur possibly jeopardizing tissue oxygenation and thus interfering with organ function.

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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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Oxygen-transporting fluids and oxygen delivery with hemodilution.

The hemodynamic effectiveness and the oxygen characteristics of stroma-free hemoglobin (SFH) solutions were studied in 11 dogs. the animals were bled two-thirds of the estimated blood volume or until cardiac arrest. The shed blood was immediately replaced by equivalent amounts of either SFH or polyhemoglobin (SFH-PLP). Sixty min later, Ringer's lactate was given iv for 180 min to maintain right atrial pressure at the initial value. In a second set of experiments, the intravascular persistence of SFH-PLP was investigated in 5 dogs by withdrawal of blood (7 ml/kg bw) and immediate replacement with 131I-labeled SFH-PLP. Hemodynamic disorders after severe blood loss could be reversed by infusion of hemoglobin solutions. Due to the short intravascular persistence, cardiac output did not increase as one would expect from the degree of hemodilution. Pyridoxalation of the hemoglobin molecule reduced oxygen affinity and improved oxygen unloading at the tissue level. The short intravascular half-time of this compound could be overcome by crosslinking of the pyridoxalated hemoglobin molecules. Further studies must prove whether this polyhemoglobin can be used as a long-term oxygen-carrying blood substitute.

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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.

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[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.

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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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