دورية أكاديمية
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Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.

التفاصيل البيبلوغرافية
العنوان: Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.
المؤلفون: Rivas VN; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Crofton AE; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Jauregui CE; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Wouters JR; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Yang BS; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Wittenburg LA; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Kaplan JL; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Hwee DT; Research and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA., Murphy AN; Research and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA., Morgan BP; Research and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA., Malik FI; Research and Non-Clinical Development, Cytokinetics, Inc., South San Francisco, CA, USA., Harris SP; Department of Physiology, University of Arizona, Tucson, AZ, USA., Stern JA; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA. jastern@ncsu.edu.; Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA. jastern@ncsu.edu.
المصدر: Scientific reports [Sci Rep] 2024 May 27; Vol. 14 (1), pp. 12038. Date of Electronic Publication: 2024 May 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Cardiomyopathy, Hypertrophic*/drug therapy , Cardiac Myosins*/metabolism, Animals ; Cats ; Cat Diseases/drug therapy ; Male ; Female ; Ventricular Outflow Obstruction/drug therapy ; Systole/drug effects ; Echocardiography ; Cross-Over Studies
مستخلص: Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.
(© 2024. The Author(s).)
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معلومات مُعتمدة: TR001861 United States TR NCATS NIH HHS; T32 HL086350 United States HL NHLBI NIH HHS; D22FE-027 Morris Animal Foundation; T34 GM136469 United States GM NIGMS NIH HHS; HL086350 United States HL NHLBI NIH HHS; K01 OD026526 United States OD NIH HHS; T32 OD011147 United States OD NIH HHS; TL1 TR001861 United States TR NCATS NIH HHS; OD011147 NIH Office of the Director; OD026526 NIH Office of the Director; GM136469 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Cat; Left ventricular outflow tract obstruction (LVOTO); Myosin-inhibitor; Obstructive hypertrophic cardiomyopathy (oHCM); Pharmacodynamics
المشرفين على المادة: EC 3.6.1.- (Cardiac Myosins)
تواريخ الأحداث: Date Created: 20240527 Date Completed: 20240527 Latest Revision: 20240604
رمز التحديث: 20240604
مُعرف محوري في PubMed: PMC11130313
DOI: 10.1038/s41598-024-62840-3
PMID: 38802475
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-024-62840-3