No abstract

Summary.  Background:  We developed a fibrinogen γ‐chain (dodecapeptide HHLGGAKQAGDV [H12])‐coated, ADP‐encapsulated liposome (H12‐[ADP]‐liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb–IIIa and augments platelet aggregation by releasing ADP. Objective:  To evaluate the efficacy of H12‐(ADP)‐liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. Methods:  Thrombocytopenia (platelets < 50 000 μL−1) was induced in rabbits by repeated blood withdrawal (100 mL kg−1 in total) and isovolemic transfusion of autologous washed red blood cells. H12‐(ADP)‐liposomes with platelet‐poor plasma (PPP), platelet‐rich plasma (PRP), PPP, ADP liposomes with PPP or H12‐(PBS)‐liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. Results:  Administration of H12‐(ADP)‐liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24 h. Administration of H12‐(ADP)‐liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12‐(phosphate‐buffered saline)‐liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25 000 platelets μL−1), the hemostatic effects of H12‐(ADP)‐liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12‐(ADP)‐liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12‐(ADP)‐liposomes. Conclusions:  H12‐(ADP)‐liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.

Summary Background External low‐frequency ultrasound (USD) in combination with microbubbles has been reported to recanalize thrombotically occluded arteries in animal models. Objective The purpose of this study was to examine the enhancing effect of thrombus‐targeted bubble liposomes (BLs) developed for fresh thrombus imaging during ultrasonic thrombolysis. Methods In vitro: after the administration of thrombus‐targeted BLs or non‐targeted BLs, the clot was exposed to low‐frequency (27 kHz) USD for 5 min. In vivo: Rabbit iliofemoral arteries were thrombotically occluded, and an intravenous injection of either targeted BLs (n = 22) or non‐targeted BLs (n = 22) was delivered. External low‐frequency USD (low intensity, 1.4 W cm−2, to 12 arteries, and high intensity, 4.0 W cm−2, to 10 arteries, for both the targeted BL group and the non‐targeted BL group) was applied to the thrombotically occluded arteries for 60 min. In another 10 rabbits, recombinant tissue‐type plasminogen activator (rt‐PA) was intravenously administered. Results In vitro: the weight reduction rate of the clot with targeted BLs was significantly higher than that of the clot with non‐targeted BLs. In vivo: TIMI grade 3 flow was present in a significantly higher number of rabbits with USD and targeted BLs than rabbits with USD and non‐targeted BLs, or with rt‐PA monotherapy. High‐intensity USD exposure with targeted BLs achieved arterial recanalization in 90% of arteries, and the time to reperfusion was shorter than with rt‐PA treatment (targeted BLs, 16.7 ± 5.0 min; rt‐PA, 41.3 ± 14.4 min). Conclusions Thrombus‐targeted BLs developed for USD thrombus imaging enhance ultrasonic disruption of thrombus both in vitro and in vivo.

In order to prevent secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we performed a noncontact determination of exposure to toxic conditions via 1215-MHz microwave radar and thermography. A toxic condition was induced by intravenous administration of lipopolysaccharide (LPS) in rabbits. The exposure to LPS was determined by linear discriminant analysis using non-contact derived variables.

This is the first study to demonstrate that noninvasive transcutaneous low-frequency US energy dilates human brachial arteries. This arterial vasodilator effect has a rapid onset (within 2 min), lasts about 20 min, and is similar in magnitude to that of FMD. The vasodilator effect of US may have diagnostic and therapeutic potential in patients with or at risk for vascular disease.