Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application

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.