Abstract 18588: Clinical, Systemic, and Pathologic Effects of Intra-Cardiac Communications Created Non-Invasively in Pigs via Therapeutic Ultrasound (Histotripsy).
Introduction: We have previously demonstrated that histotripsy (pulsed cavitational ultrasound) can create atrial septal defects in an open-chest canine model and ventricular septal defects (VSDs) transcutaneously through the intact chest of neonatal pigs. To assess potential untoward effects of these cardiac applications; the clinical, systemic, and pathological effects of histotripsy induced intra-cardiac communications were analyzed.
Methods: Sixteen 3-5kg neonatal pigs were utilized. Applied by a focused 1MHz high power ultrasound transducer outside the chest wall, histotripsy pulses were delivered to the ventricular septa. The ventricular septum was targeted secondary to lack of an appropriate window to the atrial septum in this model. Six animals were sacrificed immediately, three at 2-3 days post procedure, and 7 animals survived for one month. Brain MRIs were performed on long-term survivors. Pathological specimens were obtained at the conclusion of the study.
Results: VSDs were created in 15/16 animals. There were no fatalities. All animals thrived after the procedure with appropriate development until imaging and euthanasia 0 to 28 days after the procedure. No change in gate or feeding behavior was observed. Brain MRI and lung pathology revealed no evidence of thrombo-embolic events. No damage to intervening tissue (lung, chest wall, bone or other cardiac structures) was seen. Inspection of the ventricular septum revealed flanking injury and hemorrhage acutely that was improved after 3 days and by one month showed persistence of a discrete septal defect in 4/6 cases with no flanking hemorrhage. Histologic analysis initially revealed flanking myocyte injury and hemorrhage extending 1.2 to 4.4 mm from the defect. By one month, lesions were tightly demarcated with normal appearing myocytes directly adjacent to the created lesion.
Conclusions: Transcutaneous histotripsy is a safe and effective technique to create intra-cardiac communications non-invasively, without intermediate-term untoward systemic or clinical effects. Flanking injury observed acutely is completely reversible. With further refinement and development, histotripsy has the potential to become an effective tool for palliation of congenital heart disease.
- © 2010 by American Heart Association, Inc.