{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T08:58:49Z","timestamp":1762505929245},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,2]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            The single most important determinant of cardiac arrest outcome is the duration of ventricular fibrillation (VF) preceding delivery of a high-energy shock, because of the adverse effect of VF duration on defibrillation threshold (DFT). Although a metabolic mechanism has been proposed, hypoxia, metabolic acidosis, or alkalosis do not adversely affect DFT. However, since (1) catecholamines and adenosine levels are markedly increased during hypoxia, (2) exogenous catecholamines decrease DFT, and (3) adenosine is a potent antagonist of the electrophysiological effects of catecholamines on ventricular myocardium, we hypothesized that release of adenosine during prolonged VF adversely affects DFT and that this effect occurs through an antiadrenergic mechanism.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            DFT was determined in dogs during infusion of adenosine (300 \u03bcg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ) and dipyridamole (0.25 mg\/kg), an adenosine uptake blocker, a regimen that resulted in adenosine levels in the myocardial effluent equivalent to those achieved after 5 minutes of VF. Adenosine increased transthoracic DFT in each dog by 49\u00b114% (n=21) (mean\u00b1SEM) and transmyocardial DFT in a separate group of 10 dogs by 103\u00b116%,\n            <jats:italic>P<\/jats:italic>\n            =.0003. Pretreatment with the specific A\n            <jats:sub>1<\/jats:sub>\n            adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) 5 mg\/kg completely abolished the effects of adenosine on DFT. The effects of adenosine on DFT were also examined in the denervated state (propranolol 0.2 mg\/kg plus bilateral vagotomy). In contrast to its effect in the innervated condition, adenosine had no effect on DFT in the same dogs when denervated, 49\u00b111 versus 53\u00b110 J (\n            <jats:italic>P<\/jats:italic>\n            =NS).\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            Adenosine significantly increases transthoracic and transmyocardial DFT, effects that are mediated by the A\n            <jats:sub>1<\/jats:sub>\n            adenosine myocardial receptor through an antiadrenergic mechanism. These results suggest that enhanced release of adenosine during VF may have a deleterious effect on defibrillation and that intramyocardial delivery of a specific A\n            <jats:sub>1<\/jats:sub>\n            adenosine antagonist during VF may facilitate defibrillation and significantly reduce defibrillation threshold.\n          <\/jats:p>","DOI":"10.1161\/01.cir.91.3.838","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"838-844","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Metabolic Determinants of Defibrillation"],"prefix":"10.1161","volume":"91","author":[{"given":"Bruce B.","family":"Lerman","sequence":"first","affiliation":[{"name":"From the Department of Medicine and the Division of Cardiology, The New York Hospital\u2013Cornell Medical Center, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica D.","family":"Engelstein","sequence":"additional","affiliation":[{"name":"From the Department of Medicine and the Division of Cardiology, The New York Hospital\u2013Cornell Medical Center, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(86)80332-1"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198003000-00014"},{"key":"e_1_3_2_3_2","first-page":"1106","volume":"79","year":"1988","unstructured":"Echt DS, Black JN, Barbey JT, Coxe DR, Cato E. Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Circulation. 1988;79:1106-1117.","journal-title":"Circulation"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.81.5.2331763"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Kerber RE Pandian NG Hoyt R Jensen SR Koyanagi S Grayzel J Kieso R. Effect of ischemia hypertrophy hypoxia acidosis and alkalosis on canine defibrillation. Am J Physiol. 1983;244: H825-H831.","DOI":"10.1152\/ajpheart.1983.244.6.H825"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","unstructured":"Echt DS Cato EL Coxe DR. pH-Dependent effects of lidocaine on defibrillation energy requirements in dogs. Circulation. 1989;80: 1003-1009.","DOI":"10.1161\/01.CIR.80.4.1003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0033-0620(89)90015-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","unstructured":"Belardinelli L Isenberg G. Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes. Circ Res. 1983;53: 287-297.","DOI":"10.1161\/01.RES.53.3.287"},{"key":"e_1_3_2_9_2","first-page":"H674","volume":"248","year":"1985","unstructured":"Ruffy R, Schechtman K, Monje E. \u03b2-Adrenergic modulation of direct defibrillation energy in anesthetized dog heart. Am J Physiol. 1985;248:H674-H677.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.73.2.2867836"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1987.253.4.C500"},{"key":"e_1_3_2_12_2","first-page":"H1232","volume":"258","year":"1990","unstructured":"Shryock JC, Boykin MT, Hill JA, Belardinelli L. A new method of sampling blood for measurement of plasma adenosine. Am J Physiol. 1990;258:H1232-H1239.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(73)90517-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/13.4.314"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113136"},{"key":"e_1_3_2_16_2","first-page":"H1544","volume":"259","year":"1990","unstructured":"Deale OC, Wesley RC Jr, Morgan D, Lerman BB. Nature of defibrillation: determinism versus probabilism. Am J Physiol. 1990;259:H1544-H1550.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.1.2736745"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.1.129"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-118-4-199302150-00006"},{"key":"e_1_3_2_20_2","first-page":"450","volume":"2","year":"1988","unstructured":"Ruffy R, Monje E, Schechtman K. 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