Venules and arterioles in xenotransplanted human colon adenocarcinoma critically constrict with hyperthermia and serotonin

Abstract

Local and regional hyperthermia for treatment of cancer is often combined with radio- and chemotherapy. In this study we tested whether topically applied serotonin (5-HT) modulates tumor blood flow during local hyperthermia. The surgically unprepared ear microcirculation of anesthetized (75 mg/kg pentobarbital sodium) female nude athymic (nu/nu) mice (18–25 g) was used. Between 5 and 10 days after passaged pieces of human colon adenocarcinoma cells (1 μl) had been implanted under the dorsal epidermis of the ear, that ear (tumor diameter 1.5 mm) was fixed on a temperature-regulated stage, for measurement (via closed-circuit videomicroscopy) of the diameters of large and small (A_1–3) arterioles and venules (V_1–4), and capillaries, during local hyperthermia (28°C–45°C) and during local hyperthermia plus 1 mmol/l 5-HT. In the hyperthermia-alone group all skin vessels dilated, whereas all tumor vessels constricted with increasing temperatures. Hyperthermia combined with 5-HT caused dilation of skin arterioles, but skin venules constricted. In contrast, we observed constriction of all microvessels in human tumor xenografts with the combination of hyperthermia and 5-HT. We conclude that hyperthermia and 5-HT, applied intratumorally, could be clinically effective, since normal skin microcirculation is best protected with this treatment, while tumor blood flow is widely reduced.