Key result
Myocardial infarction induces ~3-fold greater sympathetic nerve density at the ischemic border zone.
Why the study?
The three-dimensional structure of the cardiac sympathetic nervous system and its changes after myocardial infarction have been revealed only to a limited extent by conventional methods.
Effect estimate: 2.9-fold increase in volume, 3.1-fold increase in surface area
p-value: p=<0.05
A novel 3D imaging technique using tissue clearance and immunostaining successfully visualizes and quantifies sympathetic hyperinnervation and denervation in murine hearts following myocardial infarction.
May link post-MI arrhythmias to border-zone hyperinnervation; leaves open translation from murine 3D imaging to human risk stratification.
Background The sympathetic nervous system is critical in maintaining the normal physiological function of the heart. Its dysfunction in pathological states may exacerbate the substrate for arrhythmias. Obviously, knowledge of its three-dimensional (3D) structure is important, however, it has been revealed by conventional methods only to a limited extent. In this study, a new method of tissue clearance in combination with immunostaining unravels the 3D structure of the sympathetic cardiac network as well as its changes after myocardial infarction. Methods and results Hearts isolated from adult male mice were optically cleared using the CUBIC-perfusion protocol. After making the hearts transparent, sympathetic nerves and coronary vessels were immunofluorescently labeled, and then images were acquired. The spatial distribution of sympathetic nerves was visualized not only along the epicardial surface, but also transmurally. They were distributed over the epicardial surface and penetrated into the myocardium to twist around coronary vessels, but also independent from the coronary vasculature. At 2 weeks after myocardial infarction, we were able to quantify both denervation distal from the site of infarction and nerve sprouting (hyperinnervation) at the ischemic border zone of the hearts in a 3D manner. The nerve density at the ischemic border zone was more than doubled in hearts with myocardial infarction compared to intact mice hearts (3D analyses; n = 5, p<0.05). Conclusions There is both sympathetic hyperinnervation and denervation after myocardial infarction. Both can be visualized and quantified by a new imaging technique in transparent hearts and thereby become a useful tool in elucidating the role of the sympathetic nervous system in arrhythmias associated with myocardial infarction.
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Yokoyama et al. (2017) studied Myocardial infarction (n=10). Myocardial infarction induction (coronary artery ligation) vs. Intact mice hearts was evaluated on Sympathetic nerve density at the ischemic border zone (2.9-fold increase in volume, 3.1-fold increase in surface area, p=<0.05). Myocardial infarction induced sympathetic hyperinnervation at the ischemic border zone, with nerve density increasing 2.9 times in volume and 3.1 times in surface area compared to intact hearts.
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