Cardiac Autonomic Disorders and Botulinum Toxin Treatment
Received Date: Jul 17, 2018 / Accepted Date: Aug 04, 2018 / Published Date: Aug 14, 2018
Botulinum toxin, which has a zinc-binding metalloendopeptidase function, is a bacterial endotoxin produced by Clostridium botulinum during growth and reproduction. Botulinum toxin acts at the neuromuscular junction and autonomic preganglionic and parasympathetic postganglionic neurons to inhibit the exocytotic release of acetylcholine stored in synaptic vesicles . Therefore, botulinum toxin blocks cholinergic neurotransmission at the neuromuscular junction and autonomic nerve endings, which is important for motor function and autonomic neuronal activity especially parasympathetic activity. Recently, botulinum toxin was established as a highly effective and safe treatment option for movement disorders (focal dystonias, focal spasticity, essential tremor, etc.) and autonomic disorders (focal hyperhidrosis, hypersalivation, hyperactive bladder, etc.) [2-3]. Interestingly, botulinum toxin has a markedly longer duration of action in autonomic than in motor disorders [4-5], suggesting that it is more effective for the treatment of autonomic disorders than motor disorders.
Cardiac Autonomic Disorders and Botulinum Toxin Treatment
It is well-known that autonomic nerves intensively and asymmetrically innervate the heart and regulate the cardiac function . In particular, unbalanced activation of cardiac autonomic nerves may induce cardiac rhythm disturbance such as bradycardia and tachyarrhythmia. At the beginning of this century, however, there was no available data on whether botulinum neurotoxin inhibits parasympathetic ganglionic neurotransmission in the heart, although botulinum toxin as a clinical drug inhibits the release of acetylcholine at the neuromuscular junction. As the preganglionic parasympathetic nerve endings are primarily located in the epicardial and endocardial fat pads (i.e., ganglionated plexi) close to the heart, we examined the effects of botulinum toxin on parasympathetic ganglionic activation and demonstrated that the selective injection of botulinum toxin into the sinoatrial fat pad blocked bradycardia induced by parasympathetic ganglionic activation in dog hearts . Moreover, we also demonstrated that successive conditioning low-frequency cervical vagal stimulation accelerated botulinum toxininduced inhibition of the bradycardia induced by vagal stimulation, suggesting that botulinum toxin treatment might be more effective in the setting of increased vagal tone. The existence and location of epicardial fat pads in the human heart is known to be similar to those of the canine heart . Moreover, targeting cardiac autonomic ganglia by fat pad ablation has been shown to effectively suppress atrial fibrillation . Therefore, botulinum toxin may be a highly effective and safe treatment option for parasympathetic mediated atrial fibrillation and other diseases that are aggravated by parasympathetic activation in a clinical setting. In fact, recent clinical and experimental studies demonstrated that fat pad ablation by botulinum toxin is effective for the inhibition of atrial fibrillation. For example, Oh et al.  demonstrated that the injection of botulinum toxin into the sinoatrial and atrioventricular fat pads suppressed vagally-mediated atrial fibrillation for at least 1 week with a reduced dispersion of the effective refractory period in mongrel dogs. Moreover, botulinum toxin injection into 4 epicardial fat pads provided atrial tachyarrhythmia suppression during a year without any serious adverse events in humans . However, longer-term effects of botulinum toxin treatment on atrial fibrillation suppression remain unclear. Moreover, partial atrial vagal ablation has facilitated rather than prevented the initiation of vagally mediated atrial fibrillation  (Table 1). We need to conduct further studies on the effectiveness of botulinum toxin treatment to suppress atrial fibrillation to answer the questions. Finally, we hope the broad possibilities of botulinum toxin are realized in the treatment of several autonomic disorders, including cardiac autonomic disease.
|1||Botulinum toxin injection into cardiac epicardial fat pads suppresses post-cardiac operation- and vagally-mediated atrial tachyarrhythmias without any serious adverse events.|
|2||Selective injection of botulinum toxin into the sinoatrial fat pad can block vagally-mediated-bradycardia especially in the setting of increased vagal tone.|
|3||Botulinum toxin may be a highly effective and safe treatment option for autonomically-mediated atrial fibrillation and other diseases that are aggravated by parasympathetic activation in a clinical setting.|
Table 1: Summary of botulinum toxin treatment for cardiac autonomic disorders.
- Montecucco C, Schiavo G, Tugnoli V, de Grandis D (1996) Botulinum neurotoxins: Mechanism of action and therapeutic applications. Mol Med Today 2: 418-424.
- Simpson DM, Blitzer A, Brashear A, Comella C, Dubinsky R, et al. (2008) Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70: 1699-1706.
- Naumann M, So Y, Argoff CE, Childers MK, Dykstra DD, et al. (2008) Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology, Neurology 70: 1707-1714.
- Scheffer AR, Erasmus C, van Hulst K, van Limbeek J, Jongerius PH, et al. (2010) Efficacy and duration of botulinum toxin treatment for drooling in 131 children. Arch Otolaryngol Head Neck Surg 136: 873-877.
- Sengoku A, Okamura K, Kimoto Y, Ogawa T, Namima, et al. (2015) Botulinum toxin A injection for the treatment of neurogenic detrusor overactivity secondary to spinal cord injury: Multi-institutional experience in Japan. Int J Urol 22: 306-309.
- Ardell JL, Randall WC, Cannon WJ, Schmacht DC, Tasdemiroglu E (1988) Differential sympathetic regulation of automatic, conductile and contractile tissue in dog heart. Am J Physiol 255: H1050-H1059.
- Tsuboi M, Furukawa Y, Kurogouchi F, Nakajima K, Hirose M, et al. (2002) Botulinum neurotoxin a blocks cholinergic ganglionic neurotransmission in the dog heart. Jpn J Pharmacol 89: 249-254.
- Carlson MD, Geha AS, Hsu J, Martin PJ, Levy MN, et al. (1992) Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node. Circulation 85: 1311-1317.
- Lu Z, Scherlag BJ, Lin J, Niu G, Fung KM, et al. (2008) Atrial fibrillation begets atrial fibrillation: Autonomic mechanism for atrial electrical remodeling induced by short-term rapid atrial pacing. Circ Arrhythm Electrophysiol 1: 184-192.
- Oh S, Choi EK, Zhang Y, Mazgalev TN (2011) Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation. Circ Arrhythm Electrophysiol 4: 560-565.
- Pokushalov E, Kozlov B, Romanov A, Strelnikov A, Bayramova S, et al. (2015) Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: One-year follow-up of a randomized pilot study. Circ Arrhythm Electrophysiol 8: 1334-1341.
- Hirose M, Leatmanoratn Z, Laurita KR, Carlson MD (2002) Partial vagal denervation increases vulnerability to vagally induced atrial fibrillation. J Cardiovasc Electrophysiol 13: 1272-1279.
Select your language of interest to view the total content in your interested language
Share This Article
- Total views: 1799
- [From(publication date): 0-2018 - Nov 20, 2018]
- Breakdown by view type
- HTML page views: 1773
- PDF downloads: 26