{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:01:57Z","timestamp":1787742117909,"version":"build-2784847793"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>The nitroxyl (HNO) donor, Angeli\u2019s salt, exerts positive inotropic, lusitropic, and vasodilator effects in vivo that are cAMP independent. Its clinical usefulness is limited by chemical instability and cogeneration of nitrite which itself has vascular effects. Here, we report on effects of a novel, stable, pure HNO donor (CXL-1020) in isolated myoctyes and intact hearts in experimental models and in patients with heart failure (HF).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              CXL-1020 converts solely to HNO and inactive CXL-1051 with a t\n              <jats:sub>1\/2<\/jats:sub>\n              of 2 minutes. In adult mouse ventricular myocytes, it dose dependently increased sarcomere shortening by 75% to 210% (50\u2013500 \u03bcmol\/L), with a \u224830% rise in the peak Ca\n              <jats:sup>2+<\/jats:sup>\n              transient only at higher doses. Neither inhibition of protein kinase A nor soluble guanylate cyclase altered this contractile response. Unlike isoproterenol, CXL-1020 was equally effective in myocytes from normal or failing hearts. In anesthetized dogs with coronary microembolization-induced HF, CXL-1020 reduced left ventricular end-diastolic pressure and myocardial oxygen consumption while increasing ejection fraction from 27% to 40% and maximal ventricular power index by 42% (both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). In conscious dogs with tachypacing-induced HF, CXL-1020 increased contractility assessed by end-systolic elastance and provided venoarterial dilation. Heart rate was minimally altered. In patients with systolic HF, CXL-1020 reduced both left and right heart filling pressures and systemic vascular resistance, while increasing cardiac and stroke volume index. Heart rate was unchanged, and arterial pressure declined modestly.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>These data show the functional efficacy of a novel pure HNO donor to enhance myocardial function and present first-in-man evidence for its potential usefulness in HF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifiers: NCT01096043, NCT01092325.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.113.000632","type":"journal-article","created":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T16:08:30Z","timestamp":1381421310000},"page":"1250-1258","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["Nitroxyl (HNO)"],"prefix":"10.1161","volume":"6","author":[{"given":"Hani N.","family":"Sabbah","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Gabriele","family":"Tocchetti","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjun","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantapudi","family":"Daya","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh C.","family":"Gupta","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Tunin","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Mazhari","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Takimoto","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazareno","family":"Paolocci","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Cowart","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson S.","family":"Colucci","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Kass","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI (H.N.S., M.W., R.C.G.); Department of Medicine, Division of Cardiology, The Johns Hopkins School of Medicine, Baltimore, MD (C.G.T., S.D., R.S.T., E.T., N.P., D.A.K.); Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (R.M., D.C.); Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, MA (W.S.C.); and Clinica Montevergine, Mercogliano, Italy (C.G.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.04.028"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs117"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-12-0130"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.10.910"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11936-011-0149-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr026"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-9842(02)00041-7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02968-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.12.1541"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61126-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200113"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.03.015"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3841"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.3937"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.129254"},{"key":"e_1_3_3_17_2","first-page":"614","article-title":"Nitroxyl enhances myocyte Ca2+ transients by exclusively targeting SR Ca2+-cycling.","volume":"2","author":"Kohr MJ","year":"2010","unstructured":"Kohr MJ, Kaludercic N, Tocchetti CG, Dong Gao W, Kass DA, Janssen PM, Paolocci N, Ziolo MT. 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