Nicotinamide exerts different acute effects on microcirculatory function and tissue oxygenation in rat tumors

Abstract

Purpose : Nicotinamide has been reported to preferentially radiosensitize tumor tissue, supposedly through a reduction in tumor hypoxia. This may occur as a result of nicotinamide-induced changes in tumor blood flow and therefore the present study was undertaken to evaluate the effect of nicotinamide on circulatory parameters in skeletal muscle and tumor tissue (subcutaneously-implanted DS-sarcomas) of the rat. Methods and Materials : Mean arterial blood pressure (measured in the common carotid artery using a pressure transducer) and red blood cell flux (as measured by laser Doppler flowmetry) were continuously monitored for 120 min following a single intraperitoneal application of nicotinamide (500 mg/kg). An arterial blood pressure/laser Doppler flux ratio was estimated for tumor and muscle tissue. Results : Nicotinamide significantly reduced the mean arterial blood pressure to a minimum value 25% below the pretreatment value 20 min after the commencement of drug administration, with partial recovery thereafter. Red blood cell flux through tumor tissue, following an initial rapid decrease, rose steadily to values 34% above those measured in control animals at t = 60 min, while the arterial blood pressure/laser Doppler flux ratio in tumor tissue fell to values 34% below those of control animals. In skeletal muscle similar trends were seen although the changes were not of the same extent as those seen in tumor tissue. Tumor pO 2 was measured 60 min following i.p. application of nicotinamide using polarographic needle electrodes. Despite the significant increase in blood flow following nicotinamide, no significant difference was seen between pO 2 histograms obtained in tumors in nicotinamide treated and control animals. Conclusion : These findings suggest that nicotinamide preferentially improves tumor microcirculatory function and effectuates a decrease in the arterial blood pressure/laser Doppler flux ratio within tumor tissue, effects which reach their maximum approximately 60 min following nicotinamide administration.