Photodynamic therapy (PDT) with verteporfin provides a reliable way to destroy malignant tissues. Changes in the blood flow and oxygen partial pressure (pO2) during verteporfin-PDT were studied here in the tumor tissue of the rat mammary R3230Ac carcinoma model. Oxygen microelectrodes (6-12 microns tip diameter) were used to measure the transients locally within tumors during intravenous injection of 1.0 mg/kg verteporfin followed by irradiation 15 min later with 690 nm light at 200 mW/cm2, for a cumulative dose of 144 J/cm2. The observed changes in pO2 were heterogeneous and there was a difference in the response of low-pO2 regions relative to higher-pO2 regions. The change in pO2 in hypoxic tissue regions (pO2 < 8 mmHg) had acute pO2 loss after treatment, whereas the response in regions of higher pO2 (> 8 mm Hg) was more heterogeneous with some areas maintaining their pO2 value after treatment was completed. Blood flow measurements taken on a subset of the animals indicated a significant loss in flow during the initial light delivery that remained low after treatment, indicating some vascular stasis. The results suggest that hypoxic or poorly perfused vessels may be more susceptible to acute stasis than normoxic vessels in this treatment protocol.

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Normal dogs and two Eck fistula dogs, receiving a daily diet containing an average of 1 gm. of vegetable protein per kilo of body weight, showed after average intervals of 7 to 9 weeks, slight decreases in amounts of circulating plasma protein (Table 21). A third Eck fistula dog under similar circumstances was unable to maintain its plasma protein concentration above the edema level. This dog by biopsy was shown to have an abnormal liver and the evidence indicated that the other organs were normal. The animal showed active thirst and diuresis as compared with controls (Table 25). This Eck fistula dog had less than one-tenth the capacity of the normal dog to form new plasma protein when various food proteins were added to the basal diet, and no significant quantitative differences in the relative potency of these foods (liver, kidney, heart muscle, soy bean, salmon) could be distinguished (Table 22). It appears that the liver abnormality is responsible for this abnormal reaction. This observation gives strong support to the thesis that the liver is actively concerned with fabrication of new plasma protein.

Any experimental technique which involves disturbance of liver function is of particular interest in regard to plasma protein studies, for there is evidence that the liver is associated in the production of plasma protein. When a solution of gum acacia is injected intravenously in the dog, there is a marked decrease in the blood plasma protein concentration (5). That the liver is concerned with this process is suggested by the observation that injected gum acacia is rapidly removed from the blood and deposited to a large extent in the liver, whence it is slowly eliminated in the bile (4).In any attempt to evaluate this phenomenon following gum injection, it is important to ascertain, first, whether decrease in plasma protein amcentratio~ is associated with a decrease in total circulating protein, and second, the degree of impairment of liver function under these conditions. The data given here represent such an attempt: By means of plasma volume determinations it was possible to show a decrease in the total circulating protein. Determinations of plasma fibrinogen were made as a means of estimating the relative degree of hepatic function. Marked disturbance in fibrinogen concentration was demonstrated both in dogs receiving single injections of the gum, and in those in which repeated doses were given. It was possible by means of repeated weekly injections of acacia to maintain dogs at low plasma protein and fibrinogen levels for several weeks. Following 1 We are grateful to Eli Lilly and Company for furnishing valuable material used in these experiments.

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