Giannino Giuseppe, Nocera Lorenzo, Andolfatto Maria, Braia Valentina, Giacobbe Federico, Bruno Francesco, Saglietto Andrea, Angelini Filippo, De Filippo Ovidio, D'Ascenzo Fabrizio, De Ferrari Gaetano Maria, Dusi Veronica
Cardiology, Department of Medical Sciences, University of Turin, Torino, Italy.
Division of Cardiology, Cardiovascular and Thoracic Department, 'Città della Salute e della Scienza' Hospital, Corso Bramante 88, Turin, 10126, Italy.
Bioelectron Med. 2024 Sep 13;10(1):22. doi: 10.1186/s42234-024-00153-6.
The identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far.
确定可应用于导管室的针对心肌缺血/再灌注（I/R）损伤的急性心脏保护策略，是目前尚未满足的临床需求，过去在临床前水平评估的几种干预措施在转化应用中均告失败。由异常传入信号维持的自主神经失衡是I/R损伤的关键组成部分。因此，在这种情况下，有充分的理由采用神经调节策略，旨在降低交感神经活动和/或增加迷走神经张力。在本综述中，我们重点关注颈迷走神经刺激（cVNS）和经皮耳迷走神经刺激（taVNS）；后者有可能克服侵入性cVNS的几个问题，包括可在急性情况下使用的可能性，同时保留其有益效果。首先，我们讨论I/R损伤的病理生理学，其主要是活性氧过度产生的结果。其次，我们描述自主神经系统副交感神经分支的功能解剖以及应用于电迷走神经调节的生物电子医学的最相关原理，特别关注taVNS。然后，我们详细全面地总结了侵入性和非侵入性VNS的最相关临床前研究，这些研究支持其在急性或慢性心脏损伤时，特别是在心肌I/R损伤情况下具有强大的心脏保护作用。还提到了其在心脏骤停后综合征（PCAS）这一新兴领域的潜在益处。事实上，电cVNS具有强大的抗肾上腺素能、抗炎、抗氧化、抗凋亡和促血管生成作用；大多数涉及的分子途径已直接证实在心脏水平上taVNS也会发生。临床前数据清楚地表明，VNS应用得越早，结果越好，在再灌注前及再灌注期间立即应用VNS时，有可能显著减小梗死面积并几乎完全实现左心室逆向重塑。最后，我们详细描述了迄今为止taVNS在I/R损伤方面有限但非常有前景的临床经验。
