Remote ischaemic preconditioning influences the levels of acylcarnitines in vascular surgery: a randomised clinical trial

Abstract

Background Vascular surgery patients have reduced tissues` blood supply, which may lead to mitochondrial dysfunction and accumulation of acylcarnitines (ACs). It has been suggested that remote ischaemic preconditioning (RIPC) has its organ protective effect via promoting mitochondrial function. The aim of this study was to evaluate the effect of RIPC on the profile of ACs in the vascular surgery patients. Methods This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open surgical repair of abdominal aortic aneurysm, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 min of ischaemia, followed by 5 min of reperfusion, was applied. A blood pressure cuff was used for RIPC or a sham procedure. Blood was collected preoperatively and approximately 24 h postoperatively. The profile of ACs was analysed using the AbsoluteIDQp180 kit (Biocrates Life Sciences AG, Innsbruck, Austria). Results Ninety-eight patients were recruited and randomised into the study groups and 45 patients from the RIPC group and 47 patients from the sham group were included in final analysis. There was a statistically significant difference between the groups regarding the changes in C3-OH (p = 0.023)—there was a decrease (− 0.007 µmol/L, ± 0.020 µmol/L, p = 0.0233) in the RIPC group and increase (0.002 µmol/L, ± 0.015 µmol/L, p = 0.481) in the sham group. Additionally, a decrease from baseline to 24 h after surgery (p < 0.05) was detected both in the sham and the RIPC group in the levels of following ACs: C2, C8, C10, C10:1, C12, C12:1, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2. In the sham group, there was an increase (p < 0.05) in the levels of C0 (carnitine) and a decrease in the level of C18:1-OH. In the RIPC group, a decrease (p < 0.05) was noted in the levels of C3-OH, C3-DC (C4-OH), C6:1, C9, C10:2. Conclusions It can be concluded that RIPC may have an effect on the levels of ACs and might therefore have protective effects on mitochondria in the vascular surgery patients. Further larger studies conducted on homogenous populations are needed to make more definite conclusions about the effect of RIPC on the metabolism of ACs. Trial registration ClinicalTrials.gov database, NCT02689414. Registered 24 February 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02689414.

Effects of RIPC on the Metabolome in Patients Undergoing Vascular Surgery: A Randomized Controlled Trial

“…A complete list of the analyzed metabolites is provided in Table 2 . All (acyl-) carnitines were excluded as they had been discussed in a separate paper by the same authors [ 5 ]. Forty-five more metabolites were excluded, as >33% of their pre- or postoperative values were below the level of detection (<LOD).…”

“…From 1 January 2016, to 8 February 2018, a randomized sham-controlled double-blind clinical trial was conducted at Tartu University Hospital’s Clinic of Surgery, Department of Vascular Surgery [ 3 , 4 , 5 ].…”

“…It is suggested that humoral and neural mechanisms, circulating immune cells, and activation of hypoxia-inducible genes may facilitate its effects [ 1 ]. Less focus has been given to potential alterations in patients’ metabolomes following RIPC [ 5 ]. Metabolomics can provide new insights into understanding the mechanisms of RIPC.…”

“…Several of RIPC’s beneficial effects in organ protection have been found to be mediated through pathways related to amino acid and energy metabolism [ 5 , 6 , 7 , 8 ]. However, extensive investigation is still needed, since most of the studies explaining the effects of RIPC on metabolism have been conducted on rats and need to be validated in human settings.…”

Effects of RIPC on the Metabolomical Profile during Lower Limb Digital Subtraction Angiography: A Randomized Controlled Trial

“…Research has suggested that RIPC may have the potential to significantly mitigate inflammation related risks associated with interventions, thereby potentially enhancing clinical outcomes for LEAD patients [ 11 ]. In our previous research, we demonstrated that patients receiving RIPC prior to vascular surgery exhibited altered acylcarnitine levels, suggesting potential protective effects on mitochondrial function in LEAD patients [ 12 ]. Considering that percutaneous transluminal angioplasty (PTA) and digital subtraction angiography (DSA) are likely to introduce fewer confounders than open surgery in similar settings, we hypothesized that the metabolic changes induced by RIPC might be more pronounced in this context.…”