Hepatic Tumor Neovascularity in the Rabbit Vx-2 Carcinoma Model (Microcirculation, Angiography, Velocimetry, Chemotherapy).

The morphologic structure, physiologic function, and pharmacologic response of tumor neovasculature was examined to determine if the selective delivery of diagnostic and therapeutic agents could be enhanced by the local administration of appropriate vasoactive agents. The blood supply to more than 100 tumor nodules, (diameter 15.0 mm), in 25 liver specimens, was evaluated by vascular corrosion casting, silicone rubber perfusion, and microscopy. Arterial hypervascularity at the invading edge of the tumor with progressive central necrosis in tumors > 10 mm diameter was consistently observed. Electron microscopy demonstrated that tumor neovasculature lacked both an endothelial cell lining and smooth muscle layer. Changes in arterial blood flow to normal liver and tumor nodules in response to hepatic arterial infusions of epinephrine, phenylephrine, isoproteranol, and angiotensin were determined by the tracer microsphere method and laser Doppler velocimetry. Phenylephrine was the most potent vasoconstrictor agent, decreasing blood flow to both tumors and normal liver at dose rates < 1.0 mcg/min. Isoproterenol at low dosage rates (