Noninvasive Creation of an Atrial Septal Defect by Histotripsy in a Canine Model

• DOI: 10.1161/circulationaha.109.889071
• Publication Date: 2010-02-02T03:35:19Z
• Authors: Zhen Xu; Gabe Owens; David Gordon; Charles Cain; Achi Ludomirsky
• Keywords: Atrial Septum; Embolism; Infant, Newborn; Pilot Projects; Heart Septal Defects, Atrial; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Dogs; 0302 clinical medicine; Risk Factors; Hypoplastic Left Heart Syndrome; Animals; Humans; Ultrasonics; Ultrasonography, Doppler, Color

Background—

The primary objective of this study was to develop an image-guided, noninvasive procedure to create or enlarge an atrial septal defect for the treatment of neonates with hypoplastic left heart syndrome and an intact or restrictive atrial septum. Histotripsy is an innovative ultrasonic technique that produces nonthermal, mechanical tissue fractionation through the use of high-intensity ultrasound pulses. This article reports the pilot in vivo study to create an atrial septal defect through the use of extracardiac application of histotripsy in an open-chest canine model.

Methods and Results—

In 10 canines, the atrial septum was exposed to histotripsy by an ultrasound transducer positioned outside the heart. Ultrasound pulses of 6-microsecond duration at a peak negative pressure of 15 MPa and a pulse repetition frequency of 3.3 kHz were generated by a 1-MHz focused transducer. The procedure was guided and monitored by real-time ultrasound imaging. In 9 of 10 canines, an atrial septal defect was produced, and shunting across the atrial septum was visualized. Pathology of the hearts showed atrial septal defects with minimal damage to surrounding tissue. No damage was found on the epicardial surface of the heart or other structures.

Conclusions—

Under real-time ultrasound guidance, atrial septal defects were successfully created with extracardiac histotripsy in a live canine model. Although further studies in an intact animal model are needed, these results provide promise of histotripsy becoming a valuable clinical tool.