Functional characterization of the microcirculation in tumors

Abstract

This review describes some aspects of tumor vessels and the influence of vasoactive agents on tumor blood flow, particularly the characteristic microcirculation of tumors with regard to its selective increase in blood flow. Elevation of blood pressure by infusion of angiotensin II produced a severalfold increase in tumor blood flow. The increase was selective and specific to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mm Hg. Pressure elevation by angiotensin II also selectively increased tumor oxygen tension and influx of lymph flow from the primary transplanted lesion to the lymph node metastatic lesion. Newly devised techniques for analyzing microhemodynamics of tumor vessels showed that the velocity of tumor blood flow, the vascular area in tumor tissue, and the hydrostatic pressure difference between the tumor vessel and extravascular tissue were markedly enhanced. Thus, the extravasation of material into tumor tissues can be increased by the enhancement of blood flow. This demonstration allowed the development of a new approach to cancer chemotherapy, in which the delivery to tumor tissue of systemically administered anticancer drugs can be selectively enhanced.

Effects of tumour cells on angiogenesis and vasoconstrictor responses in sponge implants in mice

“…A weak response was obtained to angiotensin II and adrenalin in neoplastic tissue only after administration of a dose 10-100 fold greater than that which evoked a response in the control neovasculature. Suzuki et al (1984) observed that newly growing tumour vessels did not react to topically administered angiotensin II. The vessels supplying tumours have been reported to be relatively unreactive to locally applied drugs which act on smooth muscle (Hirst et al, 1991).…”

“…A similar progressive loss in the capacity to react to vasoactive agents by blood vessels in experimental mammary tumours as the tumours enlarged was reported by Wickersham et al (1977). A possible explanation for the progressive loss of reactivity in tumour, but not control, implants could be that, unlike the vessels of inflammatory granulation tissue, tumour vessels are characterised by a steady progression to necrosis without any intervening stable maturation phase (Suzuki et al, 1984). Another contributing factor could be that during neoplastic growth some of the preexisting host vessels incorporated in the tumour mass disintegrate, are obstructed or are compressed (Vaupel et al, 1989).…”

“…Thus, experimental studies have suggested either increased (Young et al, 1979;Tveit et al, 1981), similar (Mattsson et al, 1982) or decreased (Wickersham et al, 1977) sensitivity to vasoactive stimuli in the tumour vascular bed compared to normal tissue. These differences have been attributed to the transplantation area of the tumour, the type of tumour and the different techniques used for measuring blood flow (Suzuki et al, 1984). The washout of locally injected radioactive '33Xe (Peterson, 1979) has been shown to be a reliable index of tumour blood flow when applied to relatively small, superficially located cancers (Kallman et al, 1972).…”

Effects of verapamil and alcohol on blood flow, melphalan uptake and cytotoxicity, in murine fibrosarcomas and human melanoma xenografts

“…Most other vasodilators also did not increase blood flow to experimental tumours, including phenoxybenzamine, isoprenaline, papaverine and hydralazine (Jirtle et al, 1978;Debreczeni et al, 1980;Mattsson et al, 1982;Chan et al, 1984). Tumour perfusion depends on the relative vascular resistance of the tumour and host circulations and on systemic blood pressure (Chan et al, 1984;Suzuki et al, 1984). Only doses of verapamil and flunarizine which reduced tumour vascular resistance without reducing blood pressure increased tumour blood flow (Kaelin et al, 1982; and the associated change in tumour FDCO would have been detectable by 86Rb.…”

Histopathological Evaluation on the Effect of Induced Hypertension Chemotherapy Presurgically Performed in Patients with Advanced Carcinoma of the Stomach.

“…histopathology ; induced hypertension chemotherapy ; angiotensin II ; gastric carcinoma Suzuki et al (1981Suzuki et al ( , 1984 in an effort to enhance the effect of cancer chemotherapy. It exploits the peculiar microcirculation of cancer tissue, where, due to lack of autoregulation which is present in ordinary tissues, blood flow is susceptible to fluctuation : The flow strongly increases when the systemic blood pressure is temporarily elevated by angiotensin II.…”