Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study

Sarah Ekeloef, Jakob Ohm Oreskov, Andreas Falkenberg, Jakob Burcharth, Anne Marie V Schou-Pedersen, Jens Lykkesfeldt, Ismail Gögenur, Sarah Ekeloef, Jakob Ohm Oreskov, Andreas Falkenberg, Jakob Burcharth, Anne Marie V Schou-Pedersen, Jens Lykkesfeldt, Ismail Gögenur

Abstract

Background: Preoperative endothelial dysfunction is a predictor of myocardial injury and major adverse cardiac events. Non-cardiac surgery is known to induce acute endothelial changes. The aim of this explorative cohort study was to assess the extent of systemic endothelial dysfunction after major emergency abdominal surgery and the potential association with postoperative myocardial injury.

Methods: Patients undergoing major emergency abdominal surgery were included in this prospective cohort study. The primary outcome was the change in endothelial function expressed as the reactive hyperemia index from 4-24 h after surgery until postoperative day 3-5. The reactive hyperemia index was assessed by non-invasive digital pulse tonometry. Secondary outcomes included changes in biomarkers of nitric oxide metabolism and bioavailability. All assessments were performed at the two separate time points in the postoperative period. Clinical outcomes included myocardial injury within the third postoperative day and major adverse cardiovascular events within 30 days of surgery.

Results: Between October 2016 and June 2017, 83 patients were included. The first assessment of the endothelial function, 4-24 h, was performed 15.8 (SD 6.9) hours after surgery and the second assessment, postoperative day 3-5, was performed 83.7 (SD 19.8) hours after surgery. The reactive hyperemia index was suppressed early after surgery and did not increase significantly; 1.64 (95% CI 1.52-177) at 4-24 h after surgery vs. 1.75 (95% CI 1.63-1.89) at postoperative day 3-5, p = 0.34. The L-arginine/ADMA ratio, expressing the nitric oxide production, was reduced in the perioperative period and correlated significantly with the reactive hyperemia index. A total of 16 patients (19.3%) had a major adverse cardiovascular event, of which 11 patients (13.3%) had myocardial injury. The L-arginine/ADMA ratio was significantly decreased at 4-24 h after surgery in patients suffering myocardial injury.

Conclusion: This explorative pathophysiological study showed that acute systemic endothelial dysfunction was present early after major emergency abdominal surgery and remained unchanged until day 3-5 after the procedure. Early postoperative disturbances in the nitric oxide bioavailability might add to the pathogenesis of myocardial injury. This pathophysiological link should be confirmed in larger studies.

Trial registration: clinicaltrials.gov no. NCT03010969.

Keywords: Abdominal surgery; Endothelial function; Myocardial injury; Perioperative medicine.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patients flowchart
Fig. 2
Fig. 2
Correlations between reactive hyperemia index and nitric oxide biomarkers. A. The correlation between reactive hyperemia index (RHI) and L-arginine. B. The correlation between RHI and asymmetric dimethyl arginine (ADMA). C. The correlation between RHI and the L-arginine/ADMA ratio. r = Pearson correlation coefficient
Fig. 3
Fig. 3
Changes in reactive hyperemia index and nitric oxide biomarkers stratified on the presence or absence of myocardial injury within the third postoperative day. Abbreviations: ADMA, asymmetric dimethyl arginine; BH2, dihydrobiopterin; BH4, tetrahydrobiopterin; MINS, myocardial injury; RHI, reactive hyperemia index

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