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Adenosine A 1 Antagonism Attenuates β ‐adrenergic–resistant Sudden Hypoxic Cardiac Insufficiency
Author(s) -
Gao Erhe,
Kaplan Justin L.,
Victain Michelle S.,
Dalsey William C.,
De Garavilla Lawrence
Publication year - 2005
Publication title -
academic emergency medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.221
H-Index - 124
eISSN - 1553-2712
pISSN - 1069-6563
DOI - 10.1197/j.aem.2005.02.006
Subject(s) - aminophylline , medicine , dobutamine , hypoxia (environmental) , adenosine , adenosine receptor , adrenergic , antagonism , oxygenation , endocrinology , anesthesia , cardiology , agonist , hemodynamics , receptor , chemistry , organic chemistry , oxygen
Objectives: In states such as hypoxia, shock, and cardiac arrest, compromised systemic oxygenation or perfusion appears to induce cardiac insufficiency that can be resistant to β ‐adrenergic drugs. Elevated levels of adenosine may mediate such β ‐adrenergic–resistant cardiac insufficiency via the adenosine A 1 receptor (A 1 AdoR). The objective of this study was to test the hypothesis that selective A 1 AdoR antagonism attenuates hypoxic cardiac insufficiency more efficaciously than β 1 ‐adrenergic agonism or nonselective adenosine antagonism. Methods: Rats were paralyzed and ventilated to a pCO 2 level of 35–40 mm Hg. Ten minutes before hypoxia (inspired O 2 concentration = 5%), rats were treated intravenously with one of the following: 0.1 mg/kg BG‐9719 ( n = 9), 10 mg/kg NPC‐205 ( n = 10; BG‐9719 and NPC‐205 are selective A 1 AdoR antagonists, with durations of action of 30–60 minutes and 60–90 minutes, respectively), 10 mg/kg aminophylline ( n = 12), 5 μ g/kg/min dobutamine ( n = 11), or control solutions. These drug doses maximized survival duration in dose‐response studies. Results: Before hypoxia, cardiac work was increased more by aminophylline and dobutamine than by BG‐9719. Mean (±SEM) duration of survival (in minutes) after hypoxia increased from <13 (control solutions) to 13.8 (±1.4) (dobutamine), 20.0 (±1.6) (aminophylline), 31.7 (±4.6) (BG‐9719), and 40.5 (±7.5) (NPC‐205) (p < 0.0001). Heart rate and dP/dt decreased rapidly after hypoxia, but decreases were attenuated with BG‐9719 and NPC‐205 compared with dobutamine (p < 0.05) and tended toward attenuation with aminophylline. Conclusions: BG‐9719 and NPC‐205 improved survival duration, heart rate, and left ventricular contractility during hypoxia more efficaciously than dobutamine and possibly aminophylline. Selective A 1 AdoR antagonists warrant further study as alternatives to β ‐adrenergic agonists in hypoxia, shock, and cardiac arrest, in which compromised systemic perfusion or oxygenation impairs cardiac output.