Bernhard Endrich

Quantitative studies of microcirculatory function in malignant tissue: Influence of temperature on microvascular hemodynamics during the early growth of the BA 1112 rat SARCOMA

Abstract Red blood cell (RBC) velocity, vessel diameter and blood flow were determined in the microcirculation of the BA 1112 sarcoma at different levels of ambient temperature. These studies were carried out in modified Algire chamber preparations utilizing television techniques in situ during a period of 7 days. At an environment temperature of 25°C, arteriolar inflow through single vessels was of the order of 10.2±4.7 × 10 −5 ml/min. As a result of increased RBC-velocity, arteriolar volume inflow through individual vessels was significantly higher at an environment temperature of 35°C (24.4±16.2 × 10−5 ml/min). In both groups, the arteriolar inflow was distributed in a similar manner. Acute hyperthermic conditions of 41.3°C decreased arteriolar inflow (3.5 ± 1.5 × 10−5 ml /min) and the number of perfused capillaries. Our findings indicate that blood supply to mesenchymal tumors can be enhanced by elevating the environmental and local temperature to 35°C. However, in comparison to room temperature conditions, the arteriolar volume inflow does not appear to perfuse an increased number of capillaries. Acute hyperthermic temperatures reduced vascularization and transparency only in the tumor portion of the chamber suggesting that microscopic blood vessels in the BA 1112 rat sarcoma can be irreversibly damaged during early growth through local application of heat.

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.

Effects of radiopaque contrast media on the microcirculation of the rabbit omentum.

Histamine concentration in plasma was measured and the microvasculature studied after injections of radiographic contrast materials and hypertonic NaCl solutions. Only 8 ml/kg of contrast material caused a prolonged decrease in systemic and microvascular pressure and a drop in erythrocyte velocity. Concomitantly, a significant increase in plasma histamine concentration was observed after two minutes. Signs of cellular defects and constriction of arterioles were noted after several minutes. These findings suggest that the hyperosmolality of the radiopaque materials tested could initiate the microhemodynamic reactions but is not responsible for cellular and endothelial damage in the microcirculation of the rabbit omentum.

Fluorocarbon emulsions as blood replacement fluid: Influence on the omental microcirculation

Abstract The results of this microvascular in vivo study indicate that, at the present, the tested fluorocarbon emulsions cannot be considered as a blood substitute for clinical applications because these solutions caused the deterioration of microhemodynamic function and caused damage to both endothelial wall and blood cells. This could only be demonstrated by methods currently used for microcirculatory research since the macrohemodynamic parameters measured were not indicative of severe side effects during the experiments. Our findings indicate that the major effect of fluorocarbon emulsions on the microcirculation is due to pharmacological action which causes arteriolar constriction, vessel wall damage, and blood cell aggregation. These effects do not appear to be a consequence of the elevated oncotic pressure. Similarly, particle size associated with a 15% emulsion could not be demonstrated to be the primary cause for the observed microhemodynamic changes. We conclude that emulsions with comparatively higher concentrations of fluorocarbon could only be utilized if their pharmacological activity on the microcirculation can be controlled.

Fluorocarbon emulsions as a synthetic blood substitute: Effects on microvascular hemodynamics in the rabbit omentum

Abstract Red blood cell (RBC) velocity, vessel diameters, and arteriolar pressures were determined in the microcirculation of the rabbit omentum after isovolemic blood replacement by means of different fluorocarbon emulsions. The measurements were carried out at different hematocrit levels utilizing television techniques in situ. The administration of a 15% (by volume) FC-47 fluorocarbon emulsion caused a slight decline of mean arterial pressure, temporary arteriolar constriction, a temporary decrease of arteriolar pressure, and a localized decrease of RBC velocity in postcapillaries and collecting venules. Damage to endothelial cells, as suggested by augmented sticking of leukocytes along the wall of the collecting venules, and destruction and conglomeration of red blood cells were consistently observed in capillaries after injection of the 15% fluorocarbon emulsion, whereas the injection of a 10% FC-43 emulsion did not induce any significant macrohemodynamic or microvascular alteration. Our findings indicate that the fluorocarbon portion of the emulsion can cause deterioration of microhemodynamic function and damage to endothelial and blood cells. More highly concentrated fluorocarbon emulsions are needed to provide the appropriate oxygen-carrying capacity but can only be utilized if they do not cause adverse reactions in the microcirculation. On the basis of these studies, it is concluded that microvascular effects of the solutions tested preclude their clinical utility.

Blood flow measurements by means of radioactive microspheres. A useful technique in malignant tumors

MEASUREMENTS of blood flow in lymphatic metastases of the SMT-2A mammary adenocarcinoma in W/Fu rats were recently reported by R. L. Jirtle [1]. Twenty-five/~m microspheres (MS), labelled with either 57Co or 113Sn, were used to differentiate between flow to the outer and central regions of tumor and tumor metastases. Even though such studies should be essential for planning and evaluating tumor treatment, there are three main drawbacks in the above study concerning the technique of utilizing radioactively labelled MS: (1) For this method to determine blood flow, MS should all be trapped in the terminal vascular bed without deteriorating the circulation. Consequently, to assess the proportion of trapped and still circulating MS, simultaneous reference sampling from the arterial and venous line is inevitable [2]. With a venous reference sample, one could distinguish between nutritional and non-nutritional flow in a malignant tumor. This differentiation has not been performed in the above study, although effective tumor treatment depends on nutritional blood flow only. (2) 240 g rats received approximately 70,000 MS. Cardiac output (CO) was calculated according to