Myocardial injury mediated by acute inflammation after abdominal surgery in mice: a mechanistic translational study.

Abstract

BACKGROUND: Perioperative myocardial injury has often been attributed to type 2 myocardial infarction, but acute systemic inflammation could also contribute. We examined the role of systemic inflammation in myocardial injury after abdominal surgery using a murine model. METHODS: Male C57BL/6 mice underwent standardised abdominal surgery or anaesthesia alone. Myocardial injury (serum cardiac troponin I [cTnI]) and systemic inflammation (serum interleukin-6 [IL-6]) were quantified (enzyme-linked immunoassay) at 1 h to 7 days after surgery with anaesthesia or anaesthesia alone. Transcriptomic changes in myocardial tissue were analysed by RNA sequencing, with protein level confirmation by immuno blotting and immunostaining. Data are presented as mean (sd). RESULTS: Surgery induced an early elevation in cTnI, peaking at 277.8 (69.0) pg mlwithin 3 h after surgery, compared with 6.8 (1.6) pg mlin anaesthesia-only controls (P<0.001). Higher cTnI levels were paralleled by serum IL-6 peaking at 3 h. Perioperative heart rate was similar between each group. RNA sequencing of myocardial tissue showed an acute inflammatory-stress response, with marked upregulated transcription of members of the pro-inflammatory S100 calcium-binding protein family, S100A8 and S100A9. Protein expression of S100A9 was predominantly increased in cardiac macrophages after surgery. Pharmacological inhibition of S100A8/A9 with the potent S100A8/A9 antagonist ABR-238901 (30 mg kg, i.p.) administered 60 min before surgery, reduced myocardial injury as indicated by lower cTnI 3 h after surgery. ABR-238901 had no effect on circulating IL-6 levels. CONCLUSIONS: Myocardial injury after abdominal surgery in mice involves a local, macrophage-mediated inflammatory response, the inhibition of which reduces postoperative cTnI elevation.