Rajiv Devanagondi, Xi Zhang, Zhen Xu, Kimberly Ives, Albert Levin, Hitinder Gurm, Gabe E. Owens

To investigate the extent and consequences of histotripsy-induced hemolysis in vivo. Porcine femoral venous blood was treated with histotripsy in 11 animals with systemic heparinization and 11 without heparin. Serum and hemodynamic measurements were obtained at 0, 2, 5, 10, 15, and 30 minutes and 48-72 hours after the procedure. Fisher exact test was used to determine differences in mortality between heparinized and nonheparinized groups. A linear mixed effects model was used to test for differences in blood analytes and hemodynamic variables over time. Of 11 animals in the nonheparinized group, 5 died during or immediately after histotripsy (45% nonheparin mortality vs 0% heparin mortality, P = .035). Serum hematocrit, free hemoglobin, lactate dehydrogenase (LDH), and right ventricular systolic pressure changed significantly (P < .001) over the treatment time. Serum hematocrit decreased slightly (from 32.5% ± 3.6% to 29.4% ± 4.2%), whereas increases were seen in free hemoglobin (from 6.2 mg/dL ± 4.6 to 348 mg/dL ± 100), LDH (from 365 U/L ± 67.8 ± to 722 U/L ± 84.7), and right ventricular systolic pressure (from 23.2 mm Hg ± 7.2 to 39.7 mm Hg ± 12.3). After 48-72 hours, hematocrit remained slightly decreased (P = .005), whereas LDH and free hemoglobin remained slightly increased compared with baseline (both P < .001). Intravascular histotripsy applied to free-flowing venous blood is safe with systemic heparinization, causing only transient hemodynamic and metabolic disturbances, supporting its use as a future noninvasive thrombolytic therapy modality.