Resistance to flow through tissue-isolated transplanted rat tumours located in two different sites

Abstract

Summary The perfusion characteristics of the P22 carcinosarcoma were investigated in tissue-isolated tumour preparations in the ovarian and inguinal fat pads of BD9 rats. Tumours were perfused with a physiological buffer of known viscosity and changes in perfusion pressure were recorded at different perfusion rates in an ex vivo system. At perfusion pressures exceeding [30][31][32][33][34][35][36][37][38][39][40] The potential importance of differentially modifying tumour perfusion as a means of enhancing some forms of cancer therapy has been recently reviewed (Jirtle, 1988;Hirst & Wood, 1989;Jain, 1990). The delivery of oxygen and other radiosensitisers is enhanced when tumour perfusion is increased, as is the delivery of chemotherapeutic agents to the tumour, whilst reducing tumour blood flow has been shown to have value in the response of tumours to hyperthermia. The identification of those factors which may be modified to produce a preferential change in tumour perfusion could have important implications for therapy.Tumour perfusion rate, q, is dependent on the pressure gradient across the tumour vascular bed, AP, and on the resistance to flow, FR, imposed by the geometric resistance of the vasculature, z, and the viscosity of the perfusing fluid, ij:Ex vivo perfusion of tissue-isolated tumours supplied by a single artery and drained by a single vein permits determination of both FR and z, if i is known, of a tumour over a range of perfusion pressures (Sevick & Jain, 1989a,b). In the rat, there are two suitable sites in which tissue-isolated tumours can be grown, the ovarian and inguinal fat pads (Gullino & Grantham, 1961;Grantham et al., 1973).One of the many problems encountered in trying to predict the outcome of various forms of cancer therapy is the variability of the response of tumours of the same type located in different sites to physiological manipulations (Hirst et al., 1991). Using the two isolated tumour models, the opportunity exists to characterise the physiological parameters governing perfusion in each site and this may provide an indication as to the mechanism behind the site dependency of tumour response to treatment. Materials and methods Animals and tumourA transplanted rat carcinosarcoma, designated P22, was used for these experiments. This tumour arose in the treated site Ovarian fat pad Ovarian-isolated tumours were implanted using the technique established by Gullino & Grantham (1961), using parafilm as the enclosing material.Inguinal fat pad A 1 -2 cm incision was made in the skin overlying the inner right thigh of male rats. The fat pad supplied by the epigastric artery was identified and cut free so that no contralateral supply was possible. The epigastric vessels were carefully cleared of any fat and connective tissue between the fat pad and the femoral vessels. The inguinal fat pad was cut so that a piece of fat ; 3-5 mm3 was left attached to the vascular pedicle. Two I mm3 tumour fragments were placed in the fat pad which was subsequently enclosed in a specially designed silic...

The response of tumour vasculature to angiotensin II revealed by its systemic and local administration to 'tissue-isolated' tumours

“…Secondly, hypervolaemia had no effect on tumour vascular resistance despite significantly increasing mean arterial blood pressure. A similar relationship between perfusion pressure and flow resistance has been found for ex vivo perfusions of the P22 tumour where systemic factors could not be involved in the response (Sensky et al, 1993 (Gullino, 1976;Vaupel et al. 1987).…”

In Vitro and In Vivo Evaluations of a Hydrophilic 64Cu-Bis(Thiosemicarbazonato)–Glucose Conjugate for Hypoxia Imaging

“…Early-generation transplants of P22 syngeneic carcinosarcomas were used for all experiments (21). The tumors were grown subcutaneously on the left flank of 7-to 9-wk-old male BDIX rats.…”

The Influence of Nitric Oxide on Tumour Vascular Tone

“…insulin (50 iu/l), sodium pyruvate (0.2 mM) and heparin ( 7 000 USP units/l). Delivery, oxygenation and warming of the buffer have been described previously (7). Pressure was monitored distal to a bubble trap in the afferent perfusion line using a physiological pressure transducer.…”