{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:58:33Z","timestamp":1791410313000,"version":"4.3.3"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,4,6]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of \u226530 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55\u00b15% versus 30\u00b17%,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.02). After tyramine, NE spillover did not change significantly in patients but increased 50\u00b110% in control subjects (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5\u00b10.05 versus 1.0\u00b10.1 \u03bcg,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105\u00b111 versus 210\u00b112 \u03bcg,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001). Baroreflex sensitivity was lower in patients (12\u00b11 versus 18\u00b12 ms\/mm Hg,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.02), but the intrinsic heart rate was similar in both groups.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.13.1706","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"1706-1712","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["Abnormal Norepinephrine Clearance and Adrenergic Receptor Sensitivity in Idiopathic Orthostatic Intolerance"],"prefix":"10.1161","volume":"99","author":[{"given":"Giris","family":"Jacob","sequence":"first","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Shannon","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Costa","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaello","family":"Furlan","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Italo","family":"Biaggioni","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Mosqueda-Garcia","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose Marie","family":"Robertson","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Robertson","sequence":"additional","affiliation":[{"name":"From the Nathan Blaser Shy-Drager Research Program, Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn, and Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-104-3-298"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(97)00133-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114878"},{"key":"e_1_3_3_4_2","first-page":"326","volume":"111","year":"1988","unstructured":"Streeten DH, Anderson GJ, Richardson R, Thomas FD. Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling. J Lab Clin Med. 1988;111:326\u2013335.","journal-title":"J Lab Clin Med"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-73-1-132"},{"key":"e_1_3_3_6_2","first-page":"S19","volume":"45","year":"1995","unstructured":"Low PA, Opfer-Gehrking TL, Textor SC, Benarroch EE, Shen WK, Schondorf R, Suarez GA, Rummans TA. Postural tachycardia syndrome (POTS). Neurology. 1995;45:S19\u2013S25.","journal-title":"Neurology"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.1_Part_1.132"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.2.575"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","unstructured":"Mosqueda-Garcia R. Evaluation of autonomic failure. In: Robertson D Biaggioni I eds. Disorders of the Autonomic Nervous System. London UK: Harwood Academic Publishers; 1995:25\u201359.","DOI":"10.1201\/9781315141367-3"},{"key":"e_1_3_3_10_2","first-page":"H581","volume":"239","year":"1980","unstructured":"Eckberg DL. Parasympathetic cardiovascular control in human disease: a critical review of methods and results. Am J Physiol. 1980;239:H581\u2013H593.","journal-title":"Am J Physiol"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.90.2.7913886"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/4.2.160"},{"key":"e_1_3_3_13_2","first-page":"I","volume":"61","year":"1987","unstructured":"Davis D, Sinoway LI, Robison J, Minotti JR, Day FP, Baily R, Zelis R. Norepinephrine kinetics during orthostatic stress in congestive heart failure. Circ Res. 1987;61:I-87\u2013I-90.","journal-title":"Circ Res"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI102445"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(82)90559-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000137495"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1958.sp006104"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(84)80264-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198606053142307"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-5-358"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.5.1072"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1966.03870110006002"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(87)90055-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","unstructured":"Davies IB Sudera D Sever PS. Endogenous agonist regulation of alpha-adrenoceptors in man. Clin Sci. 1981;61(suppl 7):207s\u2013210s.","DOI":"10.1042\/cs061207s"},{"key":"e_1_3_3_25_2","unstructured":"Hoffman BB Lefkowitz RJ. Catecholamines sympathomimetic drugs and adrenergic receptor antagonists. In: Hardman JG Limbird LE Molinoff PB Ruddon RW Gilman AG eds. Goodman & Gilman\u2019s The Pharmacological Basis of Therapeutics. New York NY: McGraw-Hill; 1996:199\u2013248."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.32.1.101"},{"key":"e_1_3_3_27_2","unstructured":"Shannon JR Jordan J Black BK Diedrich A Biaggioni I Robertson D. Sympathetic support of the circulation in idiopathic orthostatic intolerance. Circulation. 1998;98(suppl I):I-336. Abstract."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.98.20.2154"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198201000-00016"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.99.13.1706","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:33:24Z","timestamp":1715531604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.99.13.1706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4,6]]},"references-count":29,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1999,4,6]]}},"alternative-id":["10.1161\/01.CIR.99.13.1706"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.99.13.1706","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,4,6]]},"assertion":[{"value":"1998-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-04-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}