Electroanatomic remodeling of the left stellate ganglion after myocardial infarction

Abstract

Objectives: The purpose of this study was to evaluate the changes of left stellate ganglionic nerve activity (SGNA) and left thoracic vagal nerve activity (VNA) after acute myocardial infarction (MI).

Background: Whether MI results in remodeling of extracardiac nerve activity remains unclear.

Methods: We implanted radiotransmitters to record the SGNA, VNA, and electrocardiogram in 9 ambulatory dogs. After baseline monitoring, MI was created by 1-h balloon occlusion of the coronary arteries. The dogs were then continuously monitored for 2 months. Both stellate ganglia were stained for growth-associated protein 43 and synaptophysin. The stellate ganglia from 5 normal dogs were used as control.

Results: MI increased 24-h integrated SGNA from 7.44 ± 7.19 Ln(Vs)/day at baseline to 8.09 ± 7.75 Ln(Vs)/day after the MI (p < 0.05). The 24-h integrated VNA before and after the MI was 5.29 ± 5.04 Ln(Vs)/day and 5.58 ± 5.15 Ln(Vs)/day, respectively (p < 0.05). A significant 24-h circadian variation was noted for the SGNA (p < 0.05) but not the VNA. The SGNA/VNA ratio also showed significant circadian variation. The nerve densities from the left SG were 63,218 ± 34,719 μm(2)/mm(2) and 20,623 ± 4,926 μm(2)/mm(2) for growth-associated protein 43 (p < 0.05) and were 32,116 ± 8,190 μm(2)/mm(2)and 16,326 ± 4,679 μm(2)/mm(2) for synaptophysin (p < 0.05) in MI and control groups, respectively. The right SG also showed increased nerve density after MI (p < 0.05).

Conclusions: MI results in persistent increase in the synaptic density of bilateral stellate ganglia and is associated with increased SGNA and VNA. There is a circadian variation of the SGNA/VNA ratio. These data indicate significant remodeling of the extracardiac autonomic nerve activity and structures after MI.

Figure 1. Examples of SGNA and VNA After MI

Each panel shows the simultaneous recordings of the stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and subcutaneous electrocardiogram (ECG) at around 11:00 am. The SGNA and VNA increased with increasing time from myocardial infarction (MI). bpm = beats per minute; HR = average heart rate; iSGNA = integrated stellate ganglion nerve activity over 1 min; iVNA = integrated vagal nerve activity over 1 min; LSG = left stellate ganglion; VN = vagal nerve.

Figure 2. SGNA and VNA Ratio

(A, B, top) The serial changes in the ratio of integrated SGNA and VNA at different times after MI. (A, B, bottom) The comparison of baseline and after MI, which reveals significant increase in nerve activity after MI in both SGNA and VNA. (*p < 0.05 compared with baseline). Abbreviations as in Figure 1.

Figure 3. Nerve Activity and Heart Rate

The circadian changes in 1-h integrated nerve activity (i-NA) of SGNA (A) and VNA (B) for an entire day at baseline and after MI. The circadian pattern of the SGNA was maintained after MI, but VNA did not exhibit a circadian pattern. (C) Significant circadian variation in heart rate. BPM = beats per min; other abbreviations as in Figures 1 and 2.

Figure 4. Increase in SGNA and VNA After MI

(A and B) Increase in integrated SGNA and VNA after MI. There was a significant increase of SGNA in the morning to midday (A) but no change in the VNA (B). The increase in the SGNA/VNA ratio 4 and 7 weeks after MI showed significant circadian variation (C). SD of normal to normal R-R interval (SDNN) also showed significant circadian variation (D), correlating with the SGNA/VNA ratio. Int-NA = integrated nerve activity; other abbreviations as in Figures 1 and 2.

Figure 5. Immunohistochemical Staining of the Stellate Ganglia

Immunohistochemical staining with growth-associated protein 43 (upper panel) and synaptophysin (lower panel) of left and right stellate ganglia in control dogs and in dogs with myocardial infarction (MI). Arrows point to positive stains (brown). The figures show that growth-associated protein 43–positive and synaptophysin-positive nerve structures are both more prominent in myocardial infarction dogs than in control dogs. The line segments are 50 μm long.