title: Hemodynamic and Hematologic Effects of Histotripsy of Free-Flowing Blood: Implications for Ultrasound-Mediated Thrombolysis.
abstract: OBJECTIVE
  To investigate the extent and consequences of histotripsy-induced hemolysis in vivo.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Pediatric and Congenital Heart Disease, Cleveland Clinic, 9500 Euclid Avenue, M4-37A, Cleveland, OH 44915.. Electronic address: rajiv.devanagondi@gmail.com.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Devanagondi
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.; Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ives
authors.affiliation: Henry Ford Health System, Detroit, Michigan.
authors.forename: Albert
authors.initials: A
authors.lastname: Levin
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Hitinder
authors.initials: H
authors.lastname: Gurm
authors.affiliation: Michigan Congenital Heart Center, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Gabe E
authors.initials: GE
authors.lastname: Owens
mesh_terms: D000818:Animals; D001769:Blood / Q000528:radiation effects*; D001783:Blood Flow Velocity / Q000502:physiology* / Q000528:radiation effects; D006439:Hemodynamics / Q000502:physiology* / Q000528:radiation effects; D006461:Hemolysis / Q000502:physiology* / Q000528:radiation effects; D019220:High-Energy Shock Waves; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D061185:Mechanical Thrombolysis / Q000379:methods*; D013552:Swine