An experimental model was designed for direct, quantitative studies of hemodynamic and morphologic parameters in the microcirculation. It consists of implanting a modified Algire chamber in the dorsal skin flap of hamsters and the implementation of two permanent catheters in jugular vein and carotid artery. The microcirculation was studied using intravital microscopy and television techniques for in situ measurements of blood cell velocity and vascular diameters. Due to the poor contrast between blood cells, blood capillaries and surrounding s.c. tissue, microvascular beds were visualized using fluorescent microscopy after i.v. injection of 0.2 ml of 5% FITC-Dextran 150. The combination of optical elements and low amounts of FITC-Dextran improved the contrast of the televised image without changing macro- and micro-hemodynamic parameters, and blood plasma was delineated as bright structure against the substantially darker background of red blood cells and surrounding tissue. This permitted the quantitative study of practically all blood vessels within a given field of s.c. tissue in unanesthetized animals. Blood cell velocity in arterioles was 0.7-1.1 mm/s, 0.2-0.7 mm/s in midcapillaries and reached 0.6 mm/s in collecting venules. Since i.v. injection of drugs and systemic pressure measurements are possible in this model, it provides a unique means for studying the reactivity of the microcirculation over a prolonged period.
A great number of investigators have, independently, shown that tumour blood flow is affected by a hyperthermic treatment to a larger extent than normal tissue blood flow. While the majority of the studies on experimental tumours show a decrease and even a lapse in blood flow within the microcirculation during or after hyperthermia, the data on human tumours are less conclusive. Some of the investigators do not find a decrease in circulation, while others do. Obviously, this is an important field of investigation in the clinical application of hyperthermia because a shut down of the circulation would not only facilitate tumour heating (by reducing venous outflow, this reducing the 'heat clearance' from the tumour), but would also facilitate tumour cell destruction. The same holds for alterations that occur subsequently to the circulatory changes, like a heat-induced decrease of tissue pO2 and pH. If the frequently reported circulatory collapse of the tumour circulation could selectively be stimulated by, e.g. acidification or by vasoactive agents, hyperthermic treatment of patients would possibly be greatly facilitated and intensified. In hyperthermic tumour therapy a number of complex processes and interactions takes place, especially when the treatment is performed in combination with radiation therapy. One of them represents the group of processes related to the random probability of cell sterilization of individual tumour cells resulting in exponential survival curves which are typically evaluated with e.g. cell survival assays. This aspect has not been the issue of this paper. The other group of processes deals with the heat-induced changes in the micro-physiology of tumours and normal tissues which, as discussed before, may not only enhance the exponential cell kill, but which may also culminate in vascular collapse with the ensuing necrosis of the tumour tissue in the areas affected. If this takes place, a process of bulk killing of tumour cells results, rather than the random type of cell sterilization. At present it is not clear to what extent the various separate mechanisms contribute to the total effect of tumour control. With all these considerations in mind, one should be aware of the fact that effects, secondary to heat-induced vascular stasis alone will never be efficient enough to eliminate all tumour cells, even though a heat reservoir is created. This is so because some malignant cells will inevitably have already infiltrated normal, surrounding structures and will therefore not be affected by changes in the tumour vascular bed.(ABSTRACT TRUNCATED AT 400 WORDS)
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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