Introduction: Cardiac autonomic nerves are important in cardiac arrhythmogenesis. Beta-blocker is well known agent which can suppress sympathetic nerve activity. We sought to test whether carvedilol modulate sympathetic, parasympathetic or intrinsic cardiac autonomic activity (ICNA) and its influence on the onset of paroxysmal atrial tachycardia (PAT).
Method: We implanted a data sciences international (DSI) radiotransmitter in 4 dogs (male, 19.3 ± 0.5 kg) to record stellate ganglionated nerve activity (SGNA), vagal nerve activity (VNA) and superior left ganglionated plexi nerve activity (SLGPNA). After baseline recording, we recorded SGNA, VNA and SLGPNA during and after withdrawal of carvedilol (12.5 mg bid) for 7 days. The nerve discharges were quantified using integrated nerve activity (Int-NA). We analyzed the Int-NA of SGNA, VNA and SLGPNA according to carvedilol loading and withdrawal. The number of PAT episodes was also analyzed according to carvedilol status.
Results: Heart rate was slightly decreased after CVD loading (99 ± 22 bpm before carvedilol vs. 93 ± 34 bpm during carvedilol vs. 95 ± 21 bpm after withdrawal of carvedilol, p>0.05 respectively). However, Int-NAs from all channels were significantly suppressed after carvedilol loading compared to baseline (SGNA from 2.2 ± 1.5 to 1.6 ± 0.8 mV-sec, p<0.001; VNA from 1.0 ± 0.6 to 0.5 ± 0.2 mV-sec, p<0.001; SLGPNA from 1.4 ± 0.9 to 0.6 ± 0.2 mV-sec, p<0.001). After withdrawal of carvedilol, the Int-NA from all channels were consistently suppressed for 3 days compared to baseline (SGNA from 2.2 ± 1.5 to 1.7 ± 0.9 mV-sec, p=0.002; VNA from 1.0 ± 0.6 to 0.5 ± 0.2 mV-sec, p<0.001; SLGPNA from 1.4 ± 0.9 to 0.5 ± 0.2 mV-sec, p<0.001). The number of PAT episodes showed a decreasing tendency after carvedilol exposure (6.5 ± 3.1 vs. 3.5 ± 1.9 episodes/day, p=0.134), whereas PAT episodes after withdrawal of carvedilol was fewer than those at baseline (3.0 ± 2.1 vs. 6.5 ± 3.1 episodes/day, p=0.035).
Conclusion: Carvedilol could modulate not only sympathetic cardiac autonomic nerve activity but also parasympathetic and ICNA with a dose of incomplete suppression of sinus node function. Furthermore, carvedilol loading suppressed the occurrence of PAT episodes and the effect was maintained for 3 days after withdrawal in normal ambulatory canine model.
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