{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:59:11Z","timestamp":1740139151610,"version":"3.37.3"},"reference-count":56,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["13POST16810018"],"award-info":[{"award-number":["13POST16810018"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p> This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure ( P = 0.59), dP\/d t<jats:sub>max<\/jats:sub> ( P = 0.26), or dP\/d t<jats:sub>min<\/jats:sub> ( P = 0.85) in dogs. However, heart rate dose-dependently increased &gt; 70% ( P &lt; 0.01), which was accompanied by a significant increase in coronary blood flow ( P &lt; 0.05) and reductions in left ventricular end-diastolic volume and stroke volume ( P &lt; 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow ( P = 0.83) or vasorelaxation in isolated, endothelium-intact ( P = 0.89) or denuded ( P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs ( P &lt; 0.001; R<jats:sup>2<\/jats:sup>\u2009=\u20090.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species ( P &lt; 0.001; R<jats:sup>2<\/jats:sup>\u2009=\u20090.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion. <\/jats:p>","DOI":"10.1152\/ajpheart.00365.2019","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T15:55:02Z","timestamp":1582905302000},"page":"H747-H755","source":"Crossref","is-referenced-by-count":3,"title":["Distinct hemodynamic responses to (pyr)apelin-13 in large animal models"],"prefix":"10.1152","volume":"318","author":[{"given":"Johnathan D.","family":"Tune","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana E.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, 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