Acute amiodarone terminates ventricular fibrillation by modifying cellular Ca++ homeostasis in isolated perfused rat hearts.
Intravenous amiodarone has an acute antiarrhythmic action, which may be mediated by effects on intracellular calcium concentration [Ca++]i. We evaluated termination of pacing-induced ventricular fibrillation (VF) and associated changes in [Ca++]i by acute amiodarone in isolated perfused rat hearts loaded with the [Ca++]i indicator 1-(2-amino-5-(6-carboxy-2- indolyl)phenoxy)-2-(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid pentaacetoxymethyl ester. [Ca++]i was evaluated with surface fluorometry through fiberoptics placed on the interventricular septum. Two minutes after VF induction, hearts were perfused with amiodarone (n = 12, 10 micrograms/ml for 5 min followed by 1 micrograms/ml), low extracellular calcium concentration [Ca++]o (n = 12, 0.2 mM) or a control perfusate (n = 12, no treatment). VF termination during a 30-min observation period was significantly more frequent with amiodarone (92%) and with low [Ca++]o (75%) compared with no treatment (17%, P < .05). In nontreated hearts without recovery, [Ca++]i, expressed as a percentage of the base-line amplitude, increased continuously from 206% +/- 44% to 529% +/- 138% during 30-min VF (P < .05). In hearts that recovered with amiodarone and low [Ca++]o, [Ca++]i decreased significantly from 273% +/- 55% and 273% +/- 99% before treatment to 122% +/- 95% and 50% +/- 80% before defibrillation, respectively (P < .05). VF frequency was also significantly decreased with amiodarone. The nature of [Ca++]i transients in VF has not been fully known. Power spectrum analysis disclosed that [Ca++]i transients responded to every one or two electrocardiographic signals in VF with the highest frequency of 22 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)
Kojima
S
S
Department of Medicine, University of California San Francisco, USA.
Wu
S T
ST
Wikman-Coffelt
J
J
Parmley
W W
WW
D000638:Amiodarone / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone; D002118:Calcium