Adenosine A1Antagonism Attenuatesβ-adrenergic-resistant Sudden Hypoxic Cardiac Insufficiency

Autor: Erhe Gao, Lawrence de Garavilla, Justin L. Kaplan, William C. Dalsey, Michelle S. Victain
Rok vydání: 2005
Předmět:
Zdroj: Academic Emergency Medicine. 12:389-395
ISSN: 1553-2712
1069-6563
Popis: 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 beta-adrenergic drugs. Elevated levels of adenosine may mediate such beta-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 beta(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 microg/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
Databáze: OpenAIRE
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