Pathways and morphologic pattern of blood supply of epicardial ganglionated nerve plexus

The use of animal models in experimental cardiology helps to identify the functional and structural changes in the heart. Highly similar in many anatomical and physiological aspects to the human heart, the pig is often the model of choice in proof-of-principle studies related to thromboembolism, myocardial infarction and hypertrophy, heart failure, the development of coarctation of the aorta or arterial hypertension (Goldman and Raya, 1995, Tarnavski et al., 2004, Suzuki et al., 2011, Pauziene et al., 2017, Watanabe et al., 2018, Hampton, 2020).

The balance between the sympathetic and parasympathetic drive to the heart is essential for sustainable cardiac function where the autonomic sensory and motor components continuously monitor and regulate cardiac chronotropic, dromotropic and inotropic parameters (Vaseghi, and Shivkumar, 2008). Injuries of the intracardiac nerves and ganglia were previously linked to the development of myocardial infarction, heart failure, and. cardiomyopathies, where acute and/or chronic alterations of the intracardiac nervous system preceded atrial fibrillation and even lethal ventricular arrhythmias (Shen and Zipes, 2014, Chen et al., 2014, Qin et al., 2019, Goldberger et al., 2019). Therefore, a detailed description of the blood supply of the intrinsic cardiac neural plexus would allow for a better understanding of cardiac pathology and possible reasons leading to disorders of the intrinsic cardiac nervous system and their persistence during myocardial infarction, when the unbalanced activities of sympathetic and parasympathetic systems or acute chest pain appear (Thackeray et al., 2013; Goldberger et al., 2019). Furthermore, the well-known anatomy of blood supply for intrinsic cardiac ganglionated nerve plexus would guide intracardiac electrophysiological interventions aimed at ablating pulmonary veins or accessory conduction pathways, to make coronary artery bypass grafting or surgical valvuloplasty procedures safer by preserving both the epicardial neural structures and their blood vessels (Kurata et al., 1997, Gimelli et al., 2014, Gimelli et al., 2021).

Recently, a trans-coronary ethanol ablation (TCEA) was introduced as an alternative procedure for patients undergoing incessant ventricular tachycardia or atrioventricular arrhythmia (Gabus et al., 2014, Yamada et al., 2019). With advancing technologies, endocardial and epicardial radiofrequency catheter ablation (RFCA) has become the first-line therapy for the treatment of incessant ventricular tachycardia (Gabus et al., 2014). However, there are cases where RFCA is ineffective or contraindicated for certain patients. Although the application of TCEA is much less common than RFCA, the latter method remains a valuable tool for ablating sites that cannot be reached via RFCA. TCEA is indicated for ventricular tachycardia due to structural heart diseases when conventional RFCA fails (Schurmann et al., 2015). Yamada et al. (2019) reported that TCEA, using a 2 ml ethanol injection into the posterior descending artery of the right coronary artery, effectively eliminated ventricular tachycardia without affecting atrioventricular node conduction, and improved the patient’s condition to first-degree atrioventricular block. Noteworthy, TCEA may be an excellent alternative for the treatment of ventricular tachycardia after unsuccessful endocardial or epicardial RFCA in critical patients, whose arrhythmic foci are in deep, catheter-inaccessible areas of the heart (Gabus et al., 2014, Yamada et al., 2019, Flautt and Valderrábano, 2023). Undeniably, a deep understanding of the anatomy of blood supply for intrinsic cardiac ganglionated plexus is crucial for successful cardiac neuroablation employing the TCEA method, considering the potential dual and triple blood supply to certain atrial sites.

Anatomical data regarding the blood supply of spinal, cranial and, particularly, visceral nerves in humans and other animals remains scarce. Recently, it was reported that the distribution of vessels supplying the epicardial nerves on cardiac ventricles is diverse in different locations since the thicker nerves (>200 µm in diameter) near the coronary sulcus are accompanied by blood vessels, while the epicardial nerves were with the obviously thinner blood vessels, most likely pre-capillary arterioles, or they were absent entirely at the apex of the heart (Stingl et al., 2020). Epicardial nerves contain venules and postcapillary venules which are mostly located in the perineurium and there are usually two of them, while arterioles are mostly located in the endoneurium (Stingl et al., 2020; Musil et al., 2022).

The neural plexuses of the human and porcine hearts were characterized in detail by Pauza et al. (2000); Batulevicius et al. (2008); Pauziene et al. (2017); Inokaitis et al. (2022); Ragauskas et al. (2022); Tomas et al. (2022); Saburkina et al. (2022). Both the human and porcine epicardial nerve plexuses may be considered as a complex of several distinct subplexuses that contain multiple epicardial ganglia interconnected by thin interganglionic nerves (Pauza et. al., 2000; Batulevicius et al., 2008). Although the topography and structural organization of these epicardial subplexuses are comprehensively characterized, data regarding the anatomy of the blood supply of the epicardial neural plexus is limited. Therefore, the purpose of this proof-of-principle study was to trace the pathways and the anatomical pattern of blood supply to epicardial ganglia and nerves. We hypothesize that a continuous blood supply of the epicardial neural plexus may be ensured by an overlapping arterial supply in the proximal part of the epicardial plexus where many epicardial ganglia are located. Addressing this in porcine hearts would enable further pre-clinical and translational studies in humans aimed at evaluating the degree of extra-cardiac blood supply to the human heart.

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