We are developing a venovenous perfusion-induced systemic
hyperthermia (vv-PISH) system for advanced
cancer treatment. The vv-PISH system consistently delivered
hyperthermia to adult healthy swine, but significant
pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent
pulmonary hypertension. We hypothesized that
pulmonary hypertension results from decreased priming
solution air solubility, which causes pulmonary
gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming
solution preheating. In subsequent sheep (n = 7), the priming
solution was preheated (42-46°C) and the
hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C
hyperthermia. In the group lacking priming
solution preheating, significant
pulmonary hypertension (35-44 mm Hg) developed. In the sheep with priming
solution preheating, pulmonary artery pressure was very stable without
pulmonary hypertension. Blood
electrolytes were in physiologic range, and complete blood counts were unaffected by
hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming
solution preheating completely resolved the problem of
pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for
cancer treatment.