{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:16:13Z","timestamp":1784128573518,"version":"3.55.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Imaging"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Adenosine stress T1 mapping is an emerging magnetic resonance imaging method to investigate coronary vascular function and myocardial ischemia without application of a contrast agent. Using gene-modified mice and 2 vasodilators, we elucidated and compared the mechanisms of adenosine myocardial perfusion imaging and adenosine T1 mapping.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Wild-type (WT), A\n              <jats:sub>2A<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (adenosine A\n              <jats:sub>2A<\/jats:sub>\n              receptor knockout), A\n              <jats:sub>2B<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (adenosine A\n              <jats:sub>2B<\/jats:sub>\n              receptor knockout), A\n              <jats:sub>3<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (adenosine A\n              <jats:sub>3<\/jats:sub>\n              receptor knockout), and eNOS\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (endothelial nitric oxide synthase knockout) mice underwent rest and stress perfusion magnetic resonance imaging (n=8) and T1 mapping (n=10) using either adenosine, regadenoson (a selective A\n              <jats:sub>2A<\/jats:sub>\n              AR agonist), or saline. Myocardial blood flow and T1 were computed from perfusion imaging and T1 mapping, respectively, at rest and stress to assess myocardial perfusion reserve and T1 reactivity (\u0394T1). Changes in heart rate for each stress agent were also calculated. Two-way ANOVA was used to detect differences in each parameter between the different groups of mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Myocardial perfusion reserve was significantly reduced only in A\n              <jats:sub>2A<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              compared to WT mice using adenosine (1.06\u00b10.16 versus 2.03\u00b10.52,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) and regadenoson (0.98\u00b1026 versus 2.13\u00b10.75,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). In contrast, adenosine \u0394T1 was reduced compared with WT mice (3.88\u00b11.58) in both A\n              <jats:sub>2A<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (1.63\u00b11.32,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) and A\n              <jats:sub>2B<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (1.55\u00b11.35,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Furthermore, adenosine \u0394T1 was halved in eNOS\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              (1.76\u00b11.46,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) versus WT mice. Regadenoson \u0394T1 was approximately half of adenosine \u0394T1 in WT mice (1.97\u00b11.50,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), and additionally, it was significantly reduced in eNOS\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice (\u22120.22\u00b11.46,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Lastly, changes in heart rate was 2\u00d7 greater using regadenoson versus adenosine in all groups except A\n              <jats:sub>2A<\/jats:sub>\n              AR\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              , where heart rate remained constant.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              The major findings are that (1) although adenosine myocardial perfusion reserve is mediated through the A\n              <jats:sub>2A<\/jats:sub>\n              receptor, adenosine \u0394T1 is mediated through the A\n              <jats:sub>2A<\/jats:sub>\n              and A\n              <jats:sub>2B<\/jats:sub>\n              receptors, (2) adenosine myocardial perfusion reserve is endothelial independent while adenosine \u0394T1 is partially endothelial dependent, and (3) \u0394T1 mediated through the A\n              <jats:sub>2A<\/jats:sub>\n              receptor is endothelial dependent while \u0394T1 mediated through the A\n              <jats:sub>2B<\/jats:sub>\n              receptor is endothelial independent.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circimaging.120.011774","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T10:00:14Z","timestamp":1615543214000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Mechanisms of Adenosine Stress T1 Mapping"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-0603","authenticated-orcid":true,"given":"Soham A.","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering (S.A.S., C.E.R., B.A.F., F.H.E.), University of Virginia, Charlottesville, VA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9955-4916","authenticated-orcid":true,"given":"Claire E.","family":"Reagan","sequence":"additional","affiliation":[{"name":"Department of Radiology (B.A.F., F.H.E.), University of Virginia, Charlottesville, VA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-3854","authenticated-orcid":true,"given":"Brent A.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering (S.A.S., C.E.R., B.A.F., F.H.E.), University of Virginia, Charlottesville, VA."},{"name":"Department of Radiology (B.A.F., F.H.E.), University of Virginia, Charlottesville, VA."},{"name":"The Robert M. 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