Abstract
The effects of different doses of hydralazine and prostacyclin on the 31P magnetic resonance spectra of the LBDS1 fibrosarcoma were investigated and related to their effects on mean arterial blood pressure (MABP) and heart rate. The effect of reducing MABP by bleeding the animals, via the tail artery, was also investigated. Tumour spectral changes following high dose drug treatment (an increase in inorganic phosphate, a reduction in nucleotide triphosphates and a reduction in pH) were consistent with nutrient deprivation. These changes were dose dependent. Changes in MABP and heart rate were consistent with vasodilatation in normal tissues. However, for the same fall in MABP, hydralazine produced a greater rise in tumour inorganic phosphate (Pi) and a greater fall in tumour pH than did prostacyclin. Controlled bleeding was effective in reducing MABP. It also reduced tumour pH but had no significant effect on tumour Pi. The clinical application of the two drugs for reducing tumour blood flow and pH for therapy is likely to be limited by the large degree of hypotension necessary to produce an effect. The differential effect of the two drugs for the same fall in MABP may be related to different degrees of direct tumour vasodilatation or to a direct effect of hydralazine on tumour energy metabolism. The observation that controlled bleeding does not change tumour Pi is further evidence indicating that the degree of arterial hypotension is not the sole factor in determining tumour energy status.
Highlights
In order that the potential of hydralazine, prostacyclin and other vasoactive drugs can be tested clinically, a non-invasive method is required for measuring changes in tumour oxygen and nutrient status and pH, which are thought to be important for improving the types of therapy described above. 31P magnetic resonance spectroscopy (MRS) allows changes in high energy phosphates, inorganic phosphate and pH of tumours to be monitored
The purpose of the present study was to compare the effects of hydralazine and prostacyclin on the energy metabolism and pH of a transplanted rat fibrosarcoma using 31P MRS
The most significant changes are an increase in the inorganic phosphate (Pi) peak and a decrease in the nucleotide triphosphate (NTP) peaks
Summary
In order that the potential of hydralazine, prostacyclin and other vasoactive drugs (for review see Jain & Ward-Hartley, 1984) can be tested clinically, a non-invasive method is required for measuring changes in tumour oxygen and nutrient status and pH, which are thought to be important for improving the types of therapy described above. 31P magnetic resonance spectroscopy (MRS) allows changes in high energy phosphates, inorganic phosphate and pH of tumours to be monitored. In order that the potential of hydralazine, prostacyclin and other vasoactive drugs (for review see Jain & Ward-Hartley, 1984) can be tested clinically, a non-invasive method is required for measuring changes in tumour oxygen and nutrient status and pH, which are thought to be important for improving the types of therapy described above. 31P magnetic resonance spectroscopy (MRS) allows changes in high energy phosphates, inorganic phosphate and pH of tumours to be monitored. The purpose of the present study was to compare the effects of hydralazine and prostacyclin on the energy metabolism and pH of a transplanted rat fibrosarcoma using 31P MRS. Vasodilatation in normal tissues, with a consequent decrease in arterial blood pressure, would lead to a decrease in tumour blood flow, from the relationship blood flow through a tissue = arteriovenous pressure difference + vascular resistance
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