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Effect of Carvedilol on Cardiac Autonomic Nerve Activities
서울대학교병원 내과학 교실¹ Department of Medicine, Indiana University School of Medicine²
최의근¹, 오일영¹ 오세일¹ Mark J. Shen² Shien-Fong Lin² Peng-Sheng Chen²
Introduction: Autonomic nerve activities (ANA) are important in cardiac arrhythmogenesis. However, no pharmacological agents are known to suppress cardiac ANA in ambulatory animals. We tested the hypothesis that carvedilol(CVD) can effectively suppress ANA and paroxysmal atrial tachycardia (PAT) induced by high rate atrial pacing. Method: We implanted radiotransmitters to record stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA) and superior left ganglionated plexi nerve activity (SLGPNA) in 8 ambulatory dogs. CVD (12.5 mg orally twice a daily) was given for 7 days during sinus rhythm and again for 7 days after induction of sustained AF. Arbitrary unit (AU) was used to track the changes of ANA magnitude, with baseline as 1 AU. Results: Sustained AF was induced by 5 ± 2 weeks of rapid left atrial pacing . When given during sinus rhythm (Fig A), CVD significantly suppressed ANA during treatment (SGNA -24%, VNA -25% and SLGPNA -14% (p<0.05 for all vs. baseline) and for 3 days after withdrawal, along with heart rate reduction (108 ± 11 at baseline and 99 ± 10 bpm after withdrawal, p=0.033). CVD significantly reduced the incidence (from 8 ± 6 to 3 ± 3 episodes/d, p<0.05) and duration (from 68 ± 64 sec/d to 16 ± 21 sec/d, p<0.05) of baseline PAT. When CVD was given during sustained AF, 5 dogs continued AF and 3 converted to sinus rhythm. In the former dogs (n=5), the ANA were not suppressed by CVD, but increased after CVD withdrawal (SGNA 22%, VNA 11%, SLGPNA 9%, p<0.05 vs. baseline for SGNA only, Fig B). In the latter dogs (n=3), AF converted to sinus rhythm after 4 ± 2 days. There was significant reduction of SLGPNA (-74%) but not SGNA or VNA (7% and 32%, respectively, Fig C). Conclusion: CVD suppressed ANA and reduced the incidence and duration of PAT episodes in ambulatory dogs during sinus rhythm but not after induction of sustained AF. In dogs that converted to sinus rhythm, CVD selectively suppressed SLGPNA but not SGNA or VNA in the post-treatment period.
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