Abstract
Following a myocardial infarction (MI), studies have observed an increase in cardiac sympathetic nerve activity (cSNA). Sympathetic nerve activity (SNA) remains elevated and has been known to drive potentially fatal ventricular arrhythmias post-MI. Ischemic heart disease continues to be the leading cause of death, and studies around MIs and the sustained SNA increase remain prominent in the literature. MIs are known to vary greatly in size in both humans and in animal models where an infarct is induced by left anterior descending coronary artery (LAD) ligation. Many mechanistic studies utilise animal models to investigate sympathetic activation post-MI, however, many of them fail appropriately consider whether the size of infarction is a key determinant of the severity of sympathetic activation.
Our primary aim is to definitively define the relationship between size of MI and magnitude of sympathetic activation for 4 hours following an MI.
Four groups (n = 5-9/group) of male Sprague Dawley rats were used in a surgical protocol. Left thoracotomy was performed to access the heart and cardiac sympathetic nerve. MIs were induced experimentally by ligating the LAD at three distinct locations along the artery to produce small, medium, and large infarcts. The cardiac sympathetic nerve was isolated to directly measure cSNA. SNA, heart rate, and blood pressure were recorded for 4 hours post-MI induction. At the completion of the recording, the heart was perfused with triphenyl tetrazolium chloride (TTC) to selectively stain for infarcted myocardium. The heart was sectioned into 2 mm slices, photographed, and the size of the infarcted tissue was quantified as a proportion of the size of the left ventricle.
As expected, all sham animals (n = 5) survived to the end of the protocol, and interestingly all animals in the largest infarction group (Level 3, n = 8) also survived. Animals with the smallest infarctions (Level 1, n = 9) had a survival rate of 66% and animals with medium sized infarctions (Level 2, n = 5) had a survival rate of 60%. Small and large infarcts elicited a significant increase in cSNA post-MI compared to sham animals at various time points up to 240 min post-MI. There was a positive trending relationship between SNA and infarction size at 240 minutes post-MI. These results indicate that even small infarctions cause an increase in SNA, and suggests that there may be a correlation between infarct size and SNA. SNA elevation post-MI has many clinical implications and this indicates that MI size modulates cSNA, reinforcing the relevance and importance of infarct size in animal studies and patients.