Prevention of arteriovenous shunt occlusion using microbubble and ultrasound mediated thromboprophylaxis.

BACKGROUND: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts. METHODS AND RESULTS: Heparin-bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right-sided side-to-side arteriovenous (AV, carotid-jugular) shunt, and a left-sided arterio-arterial (AA, carotid-carotid) interposition shunt in each animal. After shunt implantation, animals were randomly assigned to one of 3 groups. Transcutaneous, weekly 30-minute treatments (total of 4 treatments) of either guided high MI US+MB (Group 1; n=6) using a 3% MRX-801 MB infusion, or US alone (Group 2; n=6) were given separately to each shunt. The third group of 6 pigs received no treatments. The shunts were explanted after 4 weeks and analyzed by histopathology to quantify luminal thrombus area (mm2) for the length of each shunt. No pigs received antiplatelet agents or anticoagulants during the treatment period. The median overall thrombus burden in the 3 groups for AV shunts was 5.10 mm2 compared with 4.05 mm(2) in AA (P=0.199). Group 1 pigs had significantly less thrombus burden in the AV shunts (median 2.5 mm2) compared with Group 2 (median 5.6 mm2) and Group 3 (median 7.5 mm2) pigs (P=0.006). No difference in thrombus burden was seen between groups for AA shunts. CONCLUSION: Transcutaneous US with intravenous MB is capable of preventing thrombus accumulation in arteriovenous shunts without the need for antiplatelet agents, and may be a method of preventing progressive occlusion of palliative shunts

Dual-specificity MAP kinase phosphatases in health and disease

Source at https://doi.org/10.1016/j.bbamcr.2018.09.002.It is well established that a family of dual-specificity MAP kinase phosphatases (MKPs) play key roles in the regulated dephosphorylation and inactivation of MAP kinase isoforms in mammalian cells and tissues. MKPs provide a mechanism of spatiotemporal feedback control of these key signalling pathways, but can also mediate crosstalk between distinct MAP kinase cascades and facilitate interactions between MAP kinase pathways and other key signalling modules. As our knowledge of the regulation, substrate specificity and catalytic mechanisms of MKPs has matured, more recent work using genetic models has revealed key physiological functions for MKPs and also uncovered potentially important roles in regulating the pathophysiological outcome of signalling with relevance to human diseases. These include cancer, diabetes, inflammatory and neurodegenerative disorders. It is hoped that this understanding will reveal novel therapeutic targets and biomarkers for disease, thus contributing to more effective diagnosis and treatment for these debilitating and often fatal conditions