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      Utility and safety of nafamostat mesilate for anticoagulation in dogs

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          Abstract

          Background

          Surgical interventions are recommended for cases of advanced mitral regurgitation, however, limited facilities are available. The most prominent complication in such procedures is heparin‐derived bleeding. An alternative anticoagulant to heparin, nafamostat mesilate (NM), can reduce the occurrence of complications associated with heparin such as bleeding or shock.

          Objectives

          This study aimed to evaluate the utility and safety of using NM during anaesthesia in canines.

          Methods

          Six healthy adult Beagle dogs were anaesthetised, and NM was administered intravenously as a 10 mg/kg bolus dose over 5 min, followed by a continuous infusion of 10 mg/kg/h over 20 min. Blood tests and blood pressure measurements were performed at 0, 5, 25 and 55 min after NM administration.

          Results

          Activated thromboplastin times at 0, 25 and 55 min were 13.0 ± 0.7 s, 106.7 ± 13.3 s and 28.2 ± 2.9 s, respectively, with a significant difference between 0 and 25 min ( p < 0.01) only. No significant differences were observed in prothrombin time, antithrombin, fibrinogen and fibrin degradation product concentrations between timepoints. Activated clotting times (ACTs) at 0, 5, 25 and 55 min were 119.5 ± 9.6 s, 826.7 ± 78.6 s, 924.8 ± 42.4 s and 165.2 ± 13.5 s, respectively. Significant differences were observed between 0 and 5 min ( p < 0.05) and between 0 and 25 min ( p < 0.05). Blood pressure changes occurred in four dogs (66.7%). No other serious adverse effects were observed.

          Conclusions

          ACT results indicated that NM use in anaesthetised healthy dogs was sufficient to obtain procedural anticoagulation with minimal adverse effects. However, these preliminary data require validation in further studies on cardiopulmonary bypass surgery.

          Abstract

          This study aimed to evaluate the utility and safety of using nafamostat mesilate during anesthesia in canines. Blood tests and blood pressure measurements were performed at 0, 5, 25, and 55 min after nafamostat mesilate administration. The study found activated clotting time prolongation was sufficient with nafamostat mesilate use, indicating its safety during anesthesia in healthy dogs.

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          Most cited references19

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          ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs

          Abstract This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.
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            Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments.

            FUT-175, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamstat mesilate), a novel synthetic protease-inhibiting agent, was studied to determine its in vitro effects against various proteases and other enzymes, as well as to determine its in vivo protease inhibitory effects. FUT-175 was found to inhibit, in an intense, specific and reversible way, the enzyme activities of trypsin, C1r, C1s, thrombin, kallikrein and plasmin with IC50 values of the order of 10(-6)-10(-8) M. FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, sites of inhibition being on C1r and C1s as evidenced by the intermediate-cell technique. In animal model reactions in which the complement system is known to be involved as pathogenetic factors, e.g., Forssman shock, Forssman cutaneous vasculitis, zymosan-induced paw edema, endotoxin shock and local Shwartzman reaction, FUT-175 was highly effective in that, for example, intravenous dosing at 3 mg/kg could completely protect guinea pigs from the lethal Forssman shock. FUT-175 was also found to be effective in trypsin-induced shock in mice, in lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.
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              Postoperative complications of patients undergoing cardiac surgery.

              Cardiac surgery is at high risk for the development of postoperative complications involving cardiovascular and respiratory system, as well as kidneys and central nervous system. The aim of this review is to provide an overview on the most recent findings concerning the type and incidence of different complications after cardiac surgery and to summarize the current recommendations.
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                Author and article information

                Contributors
                noriko.isayama@gmail.com
                Journal
                Vet Med Sci
                Vet Med Sci
                10.1002/(ISSN)2053-1095
                VMS3
                Veterinary Medicine and Science
                John Wiley and Sons Inc. (Hoboken )
                2053-1095
                21 November 2022
                January 2023
                : 9
                : 1 ( doiID: 10.1002/vms3.v9.1 )
                : 68-75
                Affiliations
                [ 1 ] Department of Cardiology Ueno no Mori Animal Hospital Taito Tokyo Japan
                [ 2 ] Department of Cardiovascular Surgery The Heart Institute of Japan Tokyo Women's Medical University Shinjyuku‐ku Tokyo Japan
                Author notes
                [*] [* ] Correspondence

                Noriko Isayama, Department of Cardiology, Ueno no Mori Animal Hospital, 1‐5‐11‐B1, Yanaka, Taito, Tokyo 110‐0001, Japan.

                Email: noriko.isayama@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-4240-2134
                Article
                VMS31002
                10.1002/vms3.1002
                9856972
                36408760
                f6dc2170-838e-4cec-9e98-909115fdce9d
                © 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 5, Tables: 2, Pages: 8, Words: 4190
                Categories
                Original Article
                DOGS
                Original Articles
                Custom metadata
                2.0
                January 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.3 mode:remove_FC converted:20.01.2023

                anticoagulants,cardiac surgery,cardiopulmonary bypass,mitral valve insufficiency

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