{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:16:55Z","timestamp":1790435815132,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,10,15]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>Ten percent to 20% of potential cardiac donors with brain injury and no previous cardiac history have myocardial dysfunction. We assessed components of the \u03b2-receptor\u2013G-protein\u2013adenylyl cyclase complex as well as the contractile response in 10 explanted acutely failing human hearts (donor heart dysfunction [DHD]) and compared the results with 13 age-matched nonfailing (NF) organ donor controls.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>As measured by echocardiography, all DHD hearts exhibited a decreased shortening fraction (16\u00b12%, mean\u00b1SEM). Although total and subpopulation \u03b2-receptor densities measured by [<jats:sup>125<\/jats:sup>I]iodocyanopindolol (ICYP) were similar in the DHD and NF groups, DHD hearts exhibited a 30% decrease in maximum isoproterenol-stimulated adenylyl cyclase activity and a 50% decrease in the maximal response to zinterol. DHD hearts also exhibited decreases in adenylyl cyclase maximal stimulation by forskolin (211\u00b125 [DHD] versus 295\u00b123 [NF] pmol cAMP \u00b7 min<jats:sup>\u22121<\/jats:sup>\u00b7 mg<jats:sup>\u22121<\/jats:sup>,<jats:italic>P<\/jats:italic>&lt;.05) and 5\u2032-guanylylimidodiphosphate (12.5\u00b11.8 [DHD] versus 19.6\u00b13.2 [NF] pmol cAMP \u00b7 min<jats:sup>\u22121<\/jats:sup>\u00b7 mg<jats:sup>\u22121<\/jats:sup>,<jats:italic>P<\/jats:italic>&lt;.05), but there was no significant decrease in adenylyl cyclase stimulation by Mn<jats:sup>2+<\/jats:sup>, a direct activator of adenylyl cyclase. Right ventricular trabeculae removed from DHD hearts exhibited a profound decrease in the contractile response to isoproterenol (8.7\u00b11 [DHD] versus 22\u00b12 [NF] mN,<jats:italic>P<\/jats:italic>&lt;.001) as well as reduced calcium responses (7.2\u00b11.6 [DHD] versus 14\u00b13 [NF] mN,<jats:italic>P<\/jats:italic>=.03). Morphological examination of two hearts revealed some ultrastructural evidence suggestive of catecholamine-mediated injury, but there was no difference in tissue creatine kinase activity between the two groups.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>Compared with NF hearts, DHD hearts exhibit marked uncoupling of \u03b2<jats:sub>1<\/jats:sub>- and \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors from adenylyl cyclase and contractile response stimulation as well as decreased intrinsic systolic function. Thus, acute myocardial dysfunction accompanying brain injury is characterized by marked alterations in \u03b2-adrenergic signal transduction as well as changes in the contractile apparatus, and this profile is markedly different from what occurs in the chronically failing human heart.<\/jats:p>","DOI":"10.1161\/01.cir.92.8.2183","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"2183-2189","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":123,"title":["Cardiac \u03b2-Adrenergic Neuroeffector Systems in Acute Myocardial Dysfunction Related to Brain Injury"],"prefix":"10.1161","volume":"92","author":[{"given":"Michel","family":"White","sequence":"first","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Wiechmann","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Roden","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth","family":"Hagan","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Wollmering","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. David","family":"Port","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hammond","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Abraham","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene E.","family":"Wolfel","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Lindenfeld","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fullerton","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Bristow","sequence":"additional","affiliation":[{"name":"From the Cardiology and Cardiothoracic Surgery Divisions, University of Colorado Health Sciences Center, Denver, and the University of Utah School of Medicine, Salt Lake City."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"491","volume":"10","year":"1991","unstructured":"Kriett JM, Kaye MP. 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