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Role of endogenous adenosine in atrial fibrillation after coronary artery bypass graft
Turhan Yavuz1, Barry Bertolet, Yavuz Bebooul
1University of Suleyman Demirel, School of Medicine, Department of Cardiovascular Surgery, Isparta, Turkey.
Insights
Theophylline effectively converted atrial fibrillation (AF) to sinus rhythm in patients post-coronary artery bypass graft (CABG) surgery, suggesting endogenous adenosine plays a role in early post-CABG AF.
Area of Science:
- Cardiology
- Cardiac Surgery
- Pharmacology
Background:
- Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery.
- The precise mechanisms driving post-CABG AF remain unclear, but endogenous adenosine release due to tissue hypoxia is a potential factor.
Purpose of the Study:
- To investigate if intravenous theophylline, by antagonizing adenosine A1 receptors, could resolve or alter early-onset AF (<48 hours post-CABG).
- To determine if this intervention implicates endogenous adenosine in the development of post-CABG AF.
Main Methods:
- A prospective, double-blind, placebo-controlled study involving 385 patients undergoing CABG.
- 30 patients who developed AF within 48 hours of CABG were randomized to receive intravenous theophylline (5 mg/kg) or placebo.
- Conversion to sinus rhythm within 15 minutes of administration was the primary endpoint.
Main Results:
- 53% (8/15) of patients in the theophylline group converted to sinus rhythm within 15 minutes.
- No patients in the placebo group converted to sinus rhythm within 15 minutes (p<0.007).
Conclusions:
- Adenosine A1 receptor antagonism with theophylline promptly converted many patients with early post-CABG AF to sinus rhythm.
- These findings support a mechanistic role for endogenously released adenosine in inciting early AF following CABG surgery.
Background:
Atrial fibrillation (AF) is the most common complication following coronary artery bypass graft (CABG). The mechanism of AF after CABG is not well defined; however, it is suggested that endogenous adenosine, released in response to tissue hypoxia, may play a mechanistic role in these arrhythmias.
Hypothesis:
The purpose of this study was to examine whether intravenous theophylline, via adenosine A1 receptor antagonism, would correct or modify new-onset early (<48 h post CABG) atrial fibrillation in patients post CABG, and thereby implicate endogenous adenosine as an inciting agent.
Methods:
A prospective double-blind, placebo-controlled study design was applied to 385 consecutive patients with coronary artery disease who had undergone CABG. Any patient who developed AF within 48 h of the operative procedure was randomly assigned to receive 5 mg/kg of intravenous theophylline (Group A) or matched intravenous placebo (Group B). The patients who converted to sinus rhythm within 15 min of drug administration were accepted as showing positive responses.
Results:
Thirty patients comprised the study group. In Group A, 8 of the 15 patients (53%) converted from AF to sinus rhythm within 15 min of theophylline administration. One patient who converted to sinus rhythm 20 min after theophylline administration was accepted as showing a negative response. In the placebo-treated group, no patient converted to sinus rhythm within 15 min (p<0.007 compared with Group A).
Conclusions:
The mechanism of AF after CABG is not well defined and is probably multifactorial. However, this study demonstrated that antagonism of the adenosine A1 receptor can promptly convert many of these patients back to sinus rhythm, and thereby implicates endogenously released adenosine in a mechanistic role for inciting early (<48 h) post-CABG AF.
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