Development and assessment of total thrombus-formation analysis system-based bleeding risk model in patients undergoing percutaneous coronary intervention.

BACKGROUND: Antithrombotic therapy is established for the treatment of various cardiovascular events. However, it has been shown to increase the bleeding risk. Total Thrombus-formation Analysis System (T-TAS) is reported to be useful for evaluating thrombogenicity. Here, we estimated whether T-TAS is useful for predicting bleeding events risk in patients undergoing percutaneous coronary intervention (PCI). METHODS: This was a retrospective, observational study at Kumamoto University Hospital between April 2017 and March 2019. Blood samples obtained on the day of PCI were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip). We divided the study population into 2 groups according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) (182 patients in ARC-HBR positive, 118 in ARC-HBR negative). The primary endpoint was 1-year bleeding events that were defined by Bleeding Academic Research Consortium type2, 3, or 5. RESULTS: The AR10-AUC30levels were significantly lower in the ARC-HBR positive group than in the ARC-HBR negative group (median [interquartile range] 1571.4 [1277.0-1745.3] vs. 1726.2 [1567.7-1799.6], p < 0.001). The combination of ARC-HBR and AR10-AUC30 could discriminate the bleeding risk, and improved predictive capacity compared with ARC-HBR by c-statistics. Decision-curve analysis also revealed that combining AR10-AUC30 with ARC-HBR ameliorated bleeding risk-prediction. In multivariate Cox hazards analyses, combining ARC-HBR with lower AR10-AUC30 levels was significantly associated with 1-year bleeding events. CONCLUSIONS: The results highlight that AR10-AUC30 evaluated by T-TAS could be a potentially useful marker for predicting high bleeding risk in patients undergoing PCI.

Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain.

Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [(13) N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [(13) N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [(13) N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [(13) N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [(15) O]H2 O. The reduction of [(13) N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [(13) N]ammonia may enable measurement of GS activity in the living brain.