This paper adds proof of the cardioprotective effect of remote ischaemic preconditioning. It describes the positive effect of remote ischaemic preconditioning on lowering cardiac enzymes, high sensitivity troponin T and N-terminal pro b-type natriuretic peptide (proBNP), in patients undergoing vascular surgery. There are no studies that have evaluated the effect of remote ischaemic preconditioning on N-terminal (proBNP) in vascular surgery. If the positive effect of remote ischaemic preconditioning on clinical outcomes can be proven in future studies, it would be easily applicable in patients undergoing vascular surgery. Objective:The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on preventing the leakage of cardiac damage biomarkers in patients undergoing vascular surgery. Methods: This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 minutes of ischaemia, followed by 5 minutes of reperfusion, was applied. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia. High sensitivity troponin T level was measured preoperatively and 2, 8 and 24 hours after surgery and pro b-type natriuretic peptide was measured preoperatively and 24 hours after surgery. Results: There was significantly higher leakage of high sensitivity troponin T (peak change median 2 ng/L, IQR 0.9e6.2 ng/L vs 0.6 ng/L, IQR 0.7e2.1 ng/L, p ¼ .0002) and pro b-type natriuretic peptide (change median 144 pg/mL, IQR 17e318 pg/mL vs 51 pg/mL, IQR 12e196 pg/mL, p ¼ .02) in the sham group compared to the RIPC group. Conclusion: RIPC reduces the leakage of high sensitivity troponin T and pro b-type natriuretic peptide. Therefore, it may offer cardioprotection in patients undergoing non-cardiac vascular surgery. The clinical significance of RIPC has to be evaluated in larger studies excluding the factors known to influence its effect.

WHAT THIS PAPER ADDS The current study is the first clinical study to examine the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery. Although this study failed to demonstrate a significant effect of RIPC on the arterial stiffness parameters, there was marked improvement in arterial stiffness parameters after surgery in both the interventional and the non-interventional (sham) groups. The finding that surgery itself may have an influence on arterial stiffness has some clinical impact. Objectives: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery. Methods: This was a randomised, sham controlled, double blind, single centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited. A RIPC or a sham procedure was performed, using a blood pressure cuff, along with preparation for anaesthesia. The RIPC protocol consisting of four cycles of 5 min of ischaemia, followed by 5 min of reperfusion was applied. Arterial stiffness and haemodynamic parameters were measured pre-operatively and 20e28 h after surgery. Two primary outcomes were selected: augmentation index and pulse wave velocity. Results: Ninety-eight patients were randomised. After dropouts 44 and 46 patients were included in the RIPC and sham groups, respectively. Both groups were comparable. There were no statistically significant differences in augmentation index (p ¼ .8), augmentation index corrected for heart rate of 75 beats per minute (p ¼ .8), pulse wave velocity (p ¼ .7), large artery elasticity indices (p ¼ .8), small artery elasticity indices (p ¼ .6), or mean arterial pressure (p ¼ .7) changes between the RIPC and sham groups. There occurred statistically significant (p .01) improvement in augmentation index (À5.8% vs. À5.5%), augmentation index corrected for a heart rate of 75 beats per minute (À2.5% vs. À2%), small artery elasticity indices (0.7 mL/mmHg  100 vs. 0.9 mL/mmHg  100), and mean arterial pressure post-operatively in both the RIPC and the sham groups (change median values in RIPC and sham groups, respectively). Conclusions: RIPC had no significant effect on arterial stiffness, but there was significant improvement in arterial stiffness after surgery in both groups. Arterial stiffness and haemodynamics may be influenced by surgery or anaesthesia or oxidative stress or all factors combined. Further studies are needed to clarify these findings.

Background and Aims. Perioperative kidney injury affects 12.7% of patients undergoing lower limb revascularisation surgery. Remote ischaemic preconditioning (RIPC) is a potentially protective procedure against organ damage and consists of short nonlethal episodes of ischaemia. The main objective of this substudy was to evaluate the effect of RIPC on kidney function, inflammation, and oxidative stress in patients undergoing open surgical lower limb revascularisation. Materials and Methods. This is a subgroup analysis of a randomised, sham-controlled, double-blinded, single-centre study. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia in patients undergoing open surgical lower limb revascularisation. The RIPC protocol consisted of 4 cycles of 5 minutes of ischaemia, with 5 minutes of reperfusion between every episode. Blood was collected for analysis preoperatively, 2, 8, and 24 hours after surgery, and urine was collected preoperatively and 24 hours after surgery. Results. Data of 56 patients were included in the analysis. Serum creatinine, cystatin C, and beta-2 microglobulin increased, and eGFR decreased across all time points significantly more in the sham group than in the RIPC group (p=0.021, p=0.021, p=0.024, and p=0.015, respectively). Comparison of two time points, baseline and 24 hours after surgery, revealed that the change in creatinine, eGFR, urea, cystatin C, and beta-2 microglobulin was significantly different between the groups (p<0.05). Conclusions. Our finding of reduced release of kidney injury biomarkers may indicate the renoprotective effect of RIPC in patients undergoing open surgical lower limb revascularisation. The trial is registered with ClinicalTrials.gov NCT02689414.

WHAT THIS PAPER ADDS This study evaluates for the first time the effects of remote ischaemic preconditioning (RIPC) on arterial stiffness parameters in patients with symptomatic peripheral arterial disease (PAD) undergoing digital subtraction angiography (DSA). The study shows that RIPC may modulate arterial stiffness and this effect is more pronounced in patients after stenting. As DSA is an additional risk factor in PAD patients with concomitant high cardiovascular risk, RIPC as adjunctive treatment may improve vascular function in these patients and have some clinical impact. Objectives: Remote ischaemic preconditioning (RIPC) is a phenomenon that promotes protection of tissues and organs against ischaemia reperfusion injury. RIPC has been shown to reduce myocardial and renal injury but its effect on arterial stiffness in patients undergoing lower limb digital subtraction angiography (DSA) is unknown. The aim of this study was to evaluate the effect of RIPC on arterial stiffness in patients with peripheral arterial disease (PAD) undergoing lower limb DSA. Methods: In the RIPC intervention, the blood pressure cuff on the arm was inflated to 200 mmHg or to 20 mmHg above systolic pressure, and in the sham intervention to 20 mmHg. For both, the procedure was repeated for four five minute cycles at five minute intervals between the cycles. Changes in heart rate corrected augmentation index (AIx@75), augmentation index (AIx), carotid femoral pulse wave velocity (PWV), and haemodynamic parameters were measured before and 24 h after DSA. Results: 111 (RIPC 54, sham 57) patients with symptomatic lower limb PAD scheduled for DSA were randomised. 102 patients (RIPC 47, sham 55) were included in final analysis. RIPC significantly improved AIx (À5.46% in RIPC and À1.45% in sham group; p ¼ .05), but not AIx@75 (À4.88% in RIPC and À1.38% in sham group; p ¼ .07) or PWV (À0.41 m/s in RIPC and À0.27 m/s in sham group; p ¼ .74). In the RIPC group a significant reduction in AIx (p ¼ .002) and AIx@75 (p ¼ .003) was noted after stenting when compared with the sham intervention. AIx (p ¼ .001), AIx@75 (p ¼ .002), mean arterial (p ¼ .01), peripheral (p ¼ .02), and central systolic blood pressure (p ¼ .006) were significantly reduced only in the RIPC group 24 h after DSA. Conclusion: This study evaluates for the first time the effects of RIPC on arterial stiffness parameters in patients with symptomatic PAD following DSA. RIPC may modulate arterial stiffness following a DSA procedure and is more pronounced in patients after stent placement.