NO EFFECT OF HEAD UP TILT ON TUMOR PERFUSION IN A RAT PRE‐CLINICAL MODEL OF PROSTATE CANCER

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Previous research has demonstrated an enhanced prostate tumor blood flow and oxygenation associated with the augmented mean arterial pressure during exercise. Further, prostate tumor arterioles lack functional smooth muscle and have a diminished myogenic response. Thus, we tested the hypothesis that with elevations in the heart‐to‐prostate tumor hydrostatic gradient 70° head‐up tilt (HUT) would result in an enhanced perfusion of the prostate tumor. An enhanced tumor perfusion may improve tumor oxygenation and radiation therapy outcomes.MethodsDunning AT‐1 tumor cells (1×104) were injected into the ventral prostate of male Copenhagen rats (n=7) and studies were performed ~ 6 weeks after cell injection. After 5 minutes in each body position, fluorescent microspheres (red and blue/green, ~250,000 spheres per label) were injected via the carotid artery in the level and HUT body positions. Blood flow was determined in the tumor, kidneys and soleus muscle. Vascular conductance was calculated as blood flow divided by mean arterial pressure (MAP). Blood flow and conductance rates were calculated and a two‐tailed paired t‐test was conducted to compare values in the level vs. HUT positions.ResultsAverage tumor weight was 7.1 ± 0.5 g. MAP was not different between level and HUT (p = 0.15). Adequate blood flow distribution, as determined by a <15% difference in flow between the left/right kidney and/or soleus muscle, was achieved in all animals. Tumor blood flow was not different between level and HUT (12.0 ± 1.1 vs. 10.4 ± 0.8 ml/100 g/min, respectively). No difference was observed between body positions in tumor vascular conductance (p>0.05).DiscussionContrary to our hypothesis, we did not see any significant differences in either blood flow or vascular conductance in the tumor with HUT. With HUT, the prostate shows an increase in vascular resistance; thus, the combination of immature and co‐opted host tissue arterioles present in tumors may have resulted in an unchanged perfusion of the tumor with tilt. Specifically, there would be an enhanced vascular resistance of the host‐tissue (prostate) that may counter hydrostatic differences in perfusion pressure. These findings suggest that elevations in the hydrostatic gradient via HUT may not be sufficient to enhance prostate tumor perfusion.Support or Funding InformationAmerican Cancer Society RSG 14‐150‐1‐CCE (BJB)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.