PMID- 27643992 OWN - NLM STAT- MEDLINE DCOM- 20170814 LR - 20190212 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 9 DP - 2016 TI - Disruption of Prostate Microvasculature by Combining Microbubble-Enhanced Ultrasound and Prothrombin. PG - e0162398 LID - 10.1371/journal.pone.0162398 [doi] LID - e0162398 AB - Previous studies have shown a unique method to disrupt tumor vasculature using pulsed, high-pressure amplitude therapeutic ultrasound combined with microbubbles. In this study, we attempted to destroy the prostate vasculature of canine prostates using microbubble-enhanced ultrasound (MEUS) and prothrombin. The prostates of 43 male mongrel canines were surgically exposed. Twenty-two prostates were treated using MEUS (n = 11) or MEUS and prothrombin (PMEUS, n = 11). The other 21 prostates, which were treated using microbubbles (n = 7), ultrasound (n = 7) or prothrombin (n = 7) only, served as the controls. Prothrombin was intravenously infused at 20 IU/kg. MEUS was induced using a therapeutic ultrasound device at a peak negative pressure of 4.47 MPa and a microbubble injection. Contrast-enhanced ultrasound was performed to assess the blood perfusion of the prostates. Then, the prostate tissue was harvested immediately after treatment and at 48 hours later for pathological examination. The contrast-enhanced ultrasound peak value of the prostate decreased significantly from 36.2 +/- 5.6 to 27.1 +/- 6.3 after treatment in the PMEUS group, but it remained unchanged in the other groups. Histological examination found severe microvascular rupture, hemorrhage and thrombosis in both MEUS- and PMEUS-treated prostates immediately after treatment, while disruption in the PMEUS group was more severe than in the MEUS group. Forty-eight hours after treatment, massive necrosis and infiltration of white blood cells occurred in the PMEUS group. This study demonstrated that PMEUS disrupted the normal microvasculature of canine prostates and induced massive necrosis. PMEUS could potentially become a new noninvasive method used for the treatment of benign prostatic hyperplasia. FAU - Zhang, Jinlong AU - Zhang J AD - Department of Radiology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. FAU - Wu, Shengzheng AU - Wu S AD - Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China. FAU - Liu, Yongliang AU - Liu Y AD - Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing, China. FAU - Qiao, Lu AU - Qiao L AD - Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China. FAU - Gao, Wenhong AU - Gao W AD - Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China. FAU - Zhang, Weiguo AU - Zhang W AD - Department of Radiology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. AD - State key laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. FAU - Liu, Zheng AU - Liu Z AD - Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20160919 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 9001-26-7 (Prothrombin) SB - IM MH - Animals MH - Dogs MH - High-Intensity Focused Ultrasound Ablation/*methods MH - Male MH - Microbubbles/*therapeutic use MH - Microvessels/*pathology MH - Prostate/*blood supply/pathology MH - Prostatic Hyperplasia/pathology/*therapy MH - Prothrombin/administration & dosage/*therapeutic use PMC - PMC5028116 COIS- The authors have declared that no competing interests exist. EDAT- 2016/09/20 06:00 MHDA- 2017/08/15 06:00 PMCR- 2016/09/19 CRDT- 2016/09/20 06:00 PHST- 2016/03/14 00:00 [received] PHST- 2016/07/26 00:00 [accepted] PHST- 2016/09/20 06:00 [entrez] PHST- 2016/09/20 06:00 [pubmed] PHST- 2017/08/15 06:00 [medline] PHST- 2016/09/19 00:00 [pmc-release] AID - PONE-D-16-10630 [pii] AID - 10.1371/journal.pone.0162398 [doi] PST - epublish SO - PLoS One. 2016 Sep 19;11(9):e0162398. doi: 10.1371/journal.pone.0162398. eCollection 2016.