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

Abstract

Background: remote ischemic preconditioning (RIPC) is a phenomenon in which short episodes of ischemia are applied to distant organs to prepare target organs for more prolonged ischemia and to induce protection against ischemia-reperfusion injury. This study aims to evaluate whether preoperatively performed RIPC affects the metabolome and to assess whether metabolomic changes correlate with heart and kidney injury markers after vascular surgery. Methods: a randomized sham-controlled, double-blinded trial was conducted at Tartu University Hospital. Patients undergoing elective open vascular surgery were recruited and RIPC was applied before operation. Blood was collected preoperatively and 24 h postoperatively. The metabolome was analyzed using the AbsoluteIDQ p180 Kit. Results: final analysis included 45 patients from the RIPC group and 47 from the sham group. RIPC did not significantly alter metabolites 24 h postoperatively. There was positive correlation of change in the kynurenine/tryptophan ratio with change in hs-troponin T (r = 0.570, p < 0.001), NT-proBNP (r = 0.552, p < 0.001), cystatin C (r = 0.534, p < 0.001) and beta-2-microglobulin (r = 0.504, p < 0.001) only in the RIPC group. Conclusions: preoperative RIPC did not significantly affect the metabolome 24 h after vascular surgery. The positive linear correlation of kynurenine/tryptophan ratio with heart and kidney injury markers suggests that the kynurenine–tryptophan pathway can play a role in RIPC-associated cardio- and nephroprotective effects.

The effect of short‐term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study

“…A clear understanding of rIPC may contribute to evaluating its role in preventing ischemia-related organ injury, while the exact mechanisms of rIPC remain unclear. 24 Previous studies suggested that humoral and neuronal mechanisms, circulating immune cells, and hypoxia-induced gene activation may contribute to its effects. 25 Tong and colleagues reported that rIPC can significantly increase humoral stromal cell-derived factor-1 alpha (hSDF-1α) levels in hypertension.…”

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

“…A significant decrease in glutamate levels during maximal ischemia and 24 h hours after lower limb surgery (−29% and −51%, respectively) has been described earlier, indicating that glutamate usage is upregulated both during and after ischemia [ 25 ]. Elevated glutamate levels following RIPC have been previously observed in both human and animal studies, implying an enhancement in energy metabolism to accommodate increased demand [ 21 , 26 , 27 ]. Our results align with these findings, as a significant change in glutamate levels was noted between the groups, with levels only reduced in the sham group.…”

“…Contrarily, similar patients undergoing vascular surgery did not exhibit significant changes in lysoPCs and PCs. This may be due to the greater metabolic disturbance from open surgery compared to the relatively less invasive stent placement procedure [ 13 , 26 , 34 ]. As the research of lysoPCs used as signal molecules is still scarce, further studies are needed to fully comprehend the changes and pathways seen in the RIPC group.…”