Transmural pattern of sympathetic nerve damage in a rat model of chronic myocardial infarction

Objectives After myocardial infarction (MI), clinical studies show impaired sympathetic innervation of the viable infarct borderzone. This is thought to be relevant for ventricular remodeling and arrhythmia. We investigated whether the rat could serve as a model to study the biology of regional neuronal impairment in chronic MI.

Methods Thoracotomy, followed by 20 min coronary occlusion and reperfusion was performed in 7 male Wistar rats. After 2 months (n=3) and 8 months (n=4), the catecholamine analogue C-11 hydroxyephedrine (HED, 2mCi), and the perfusion tracer Tl-201 (4uCi) were injected intravenously. Animals were sacrificed, heart was extracted, frozen and sliced for dual tracer autoradiography and HE histological analysis.

Results Non-transmural scar was identified in all animals on histology. Unlike in humans, the fibrotic area was located at the mid-myocardial level, with viable portions at both endo- and epicardial side (see figure). Tl-201 defect was well matched with the scar area. On the other hand, reduced HED uptake was found to exceed scar on the endocardial side. HED uptake ratio (vs. remote) at the endocardial portion (0.30±0.05) was significantly lower than Tl-201 (0.81±0.09, p<.001), while it was comparably low at the mid-myocardial level (0.35±0.12), and comparably high at the epicardial level (1.00±0.05).

Conclusions Non-transmural myocardial infarction in rats results in a distinct pattern of mid-myocardial scar. Sympathetic nerve integrity was impaired not only in the infarct area but also in the viable endocardial borderzone. This is probably because nerve axons travel from epicardium to endocardium, so that myocardium distal of scar has persistent neuronal damage. While the rat model provides interesting pathophysiologic insights, it is not a good reflection of the human situation, where nontransmural scar is found on the endocardial level first