Cardiac sympathetic hyperinnervation after myocardial infarction: a systematic review and qualitative analysis
Creators: name: Chen, H. Sophia
name: van Roon, Lieke
name: Schoones, Jan
name: Zeppenfeld, Katja
name: DeRuiter, Marco C.
name: Jongbloed, Monique R. M.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Physiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Biological Sciences not elsewhere classified
subject: Developmental Biology
subject: Science Policy

description: Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac sympathetic hyperinnervation remain underexposed. To provide a systematic review on cardiac sympathetic hyperinnervation after MI, taking into account: (1) definition, experimental model and quantification method and (2) location, amount and timing, in order to obtain an overview of current knowledge and to expose gaps in literature. References on cardiac sympathetic hyperinnervation were screened for inclusion. The included studies received a full-text review and quality appraisal. Relevant data on hyperinnervation were collected and qualitatively analysed. Our literature search identified 60 eligible studies performed between 2000 and 2022. Cardiac hyperinnervation is generally defined as an increased sympathetic nerve density or increased number of nerves compared to another control group (100%). Studies were performed in a multitude of experimental models, but most commonly in male rats with permanent left anterior descending (LAD) artery ligation (male: 63%, rat: 68%, permanent ligation: 93%, LAD: 97%). Hyperinnervation seems to occur mainly in the borderzone. Quantification after MI was performed in regions of interest in µm<sup>2</sup>/mm<sup>2</sup> (41%) or in percentage of nerve fibres (46%) and the reported amount showed a great variation ranging from 439 to 126,718 µm<sup>2</sup>/mm<sup>2</sup>. Hyperinnervation seems to start from three days onwards to &gt;3 months without an evident peak, although studies on structural evaluation over time and in the chronic phase were scarce. Cardiac sympathetic hyperinnervation after MI occurs mainly in the borderzone from three days onwards and remains present at later timepoints, for at least 3 months. It is most commonly studied in male rats with permanent LAD ligation. The amount of hyperinnervation differs greatly between studies, possibly due to differential quantification methods. Further studies are required that evaluate cardiac sympathetic hyperinnervation over time and in the chronic phase, in transmural sections, in the female sex, and in MI with reperfusion. KEY MESSAGESCardiac sympathetic hyperinnervation occurs three days after MI mainly in the borderzone and remains present at all timepoints.It is most commonly studied in male rats with permanent LAD ligation.The amount of hyperinnervation differs greatly between studies, possibly due to the differential quantification methods. Cardiac sympathetic hyperinnervation occurs three days after MI mainly in the borderzone and remains present at all timepoints. It is most commonly studied in male rats with permanent LAD ligation. The amount of hyperinnervation differs greatly between studies, possibly due to the differential quantification methods.