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Can exercise training enhance the repeated remote ischaemic preconditioning stimulus on peripheral and cerebrovascular function in high-risk individuals?
Maxwell, JD, France, M, Finnigan, LEM, Carter, HH, Thijssen, DHJ, Jones, H
European journal of applied physiology. 2021;(4):1167-1178
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Abstract
BACKGROUND Repeated exposure to remote ischaemic preconditioning (rIPC; short bouts of non-lethal ischaemia) enhances peripheral vascular function within 1 week; whereas, longer periods of rIPC (~ 1 year) may improve cerebral perfusion. Increasing the 'dose' of rIPC may lead to superior effects. Given the similarities between exercise and rIPC, we examined whether adding exercise to the rIPC stimulus leads to greater adaptation in systemic vascular function. METHODS Nineteen individuals with increased risk for cardiovascular disease (CVD) were randomly allocated to either 8 weeks of rIPC (n = 9) or 8 weeks of rIPC + exercise (rIPC + Ex) (n = 10). rIPC was applied three times per week in both conditions, and exercise consisted of 50 min (70% heart rate max) of cycling 3 times per week. Peripheral endothelial function was assessed using flow-mediated dilation (FMD) before and after ischaemia-reperfusion (IR). Cerebrovascular function was assessed by dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVR), and cardio-respiratory fitness (VO2peak) using a maximal aerobic capacity test. RESULTS FMD% increased by 1.6% (95% CI, 0.4, 2.8) following rIPC + Ex and by 0.3% (- 1.1, 1.5) in the only rIPC but this did not reach statistical significance (P = 0.65). Neither intervention evoked a change in dCA or in CVR (P > 0.05). VO2peak increased by 2.8 ml/kg/min (1.7, 3.9) following the rIPC + Ex and by 0.1 ml/kg/min (- 1.0, 1.4) following the rIPC only intervention (P = 0.69). CONCLUSION Combining exercise with rIPC across an 8-week intervention does not lead to superior effects in cerebrovascular and peripheral vascular function compared to a repeated rIPC intervention in individuals at risk of CVD.
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Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study.
Otsuka, H, Miyoshi, T, Ejiri, K, Kohno, K, Nakahama, M, Doi, M, Munemasa, M, Murakami, M, Nakamura, K, Ito, H
Acta medica Okayama. 2021;(1):45-53
Abstract
Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI.
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Concurrent adaptations in maximal aerobic capacity, heat tolerance, microvascular blood flow and oxygen extraction following heat acclimation and ischemic preconditioning.
Waldron, M, Papavasileiou, G, Jeffries, O, Nevola, V, Heffernan S, M, Kilduff, L, Tallent, J
Journal of thermal biology. 2020;:102724
Abstract
We investigated the effects of: 1) Ischemic pre-conditioning (IPC) plus a concurrent five-day heat acclimation + IPC (IPC + HA), 2) five-day HA with sham IPC (HA), or 3) control (CON) on thermoneutral measurements of endurance performance, resting measures of skeletal muscle oxygenation and blood flow. Twenty-nine participants were randomly allocated to three groups, which included: 1) five-days of repeated leg occlusion (4 x 5-min) IPC at limb occlusive pressure, plus fixed-intensity (55% V˙ O2max) cycling HA at ~36 °C/40% humidity; 2) HA plus sham IPC (20 mmHg) or 3) or CON (thermoneutral 55% V˙ O2max plus sham IPC). In IPC + HA and HA, there were increases in maximal oxygen consumption (O2max) (7.8% and 5.4%, respectively; P < 0.05), ventilatory threshold (VT) (5.6% and 2.4%, respectively, P < 0.05), delta efficiency (DE) (2.0% and 1.4%, respectively; P < 0.05) and maximum oxygen pulse (O2pulse-Max) (7.0% and 6.9%, respectively; P < 0.05) during an exhaustive incremental test. There were no changes for CON (P > 0.05). Changes (P < 0.05) in resting core temperature (TC), muscle oxygen consumption (m V˙ O2), and limb blood flow (LBF) were also found pre-to-post intervention among the HA and IPC + HA groups, but not in CON (P > 0.05). Five-days of either HA or IPC + HA can enhance markers of endurance performance in cooler environments, alongside improved muscle oxygen extraction, blood flow, exercising muscle efficiency and O2 pulse at higher intensities, thus suggesting the occurrence of peripheral adaptation. Both HA and IPC + HA enhance the adaptation of endurance capacity, which might partly relate to peripheral changes.
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Ischemic preconditioning prevents impact of prolonged sitting on glucose tolerance and markers of cardiovascular health but not cerebrovascular responses.
Horiuchi, M, Thijssen, DHJ
American journal of physiology. Endocrinology and metabolism. 2020;(5):E821-E826
Abstract
Prolonged, uninterrupted sitting is demonstrated to acutely impair glucose homeostasis, but it also leads to detrimental cardiovascular health effects. We examined whether ischemic preconditioning (IPC) prevents the impact of prolonged sitting-induced glucose intolerance and measured related influencing factors such as (para)sympathetic nerve activity [assessed by heart rate variability (HRV)] and blood pressure during 2 h of prolonged sitting. In this randomized, controlled crossover study, 15 healthy participants (80% men) with a mean age of 21 ± 1 yr (means ± SD) and body mass index of 25.0 ± 2.4 kg/m2 performed IPC (IPC, 4 × 5-min 220-mmHg unilateral occlusion at the thigh muscle) or a sham intervention (sham, 4 × 5 min 20-mmHg), followed by 2 h of sitting. After IPC or sham intervention, fingertip blood glucose was measured before and after 30, 60, 90, and 120 min of 75 g of glucose ingestions. Blood glucose responses during an oral glucose tolerance test were significantly attenuated, resulting in a lower area under the curve when sitting was preceded by a bout of IPC than sham (P < 0.05). IPC increased high-frequency oscillations and decreased the ratio of low-frequency-to-high-frequency oscillations at 120 min in HRV (P < 0.05). Moreover, a lower blood pressure was observed with IPC compared with sham (P < 0.05). Prolonged sitting or IPC did not affect cerebrovascular responses (P > 0.05). Collectively, these results indicate that the application of IPC before prolonged, uninterrupted sitting bout was associated with a better glucose tolerance and prevented impairment in (para)sympathetic nerve activity and blood pressure in healthy young men and women.
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Remote ischemic preconditioning for prevention of contrast-induced nephropathy - A randomized control trial.
Bafna, AA, Shah, HC
Indian heart journal. 2020;(4):244-247
Abstract
BACKGROUND There is a lack of sufficient data regarding the protective effects of remote ischemic preconditioning (RIPC) in patients at risk of developing contrast-induced nephropathy (CIN). Thus, this study was conducted to determine whether RIPC as an adjunct to standard therapy prevents CIN in high-risk patients undergoing coronary intervention. METHODS In a single-center, double-blinded, randomized controlled trial, 162 patients who were at risk of CIN received standard hydration combined with RIPC or hydration with sham preconditioning. RIPC was accomplished by four cycles of 5 min ischemia and 5 min reperfusion of the forearm. The primary endpoint was a rise in serum creatinine (>0.5 mg/dL or >25%) from baseline to serum creatinine 48-72 h after contrast administration. RESULTS Of the 162 patients, 81 were randomly allocated to receive sham preconditioning and 81 to receive RIPC. Significantly reduced serum creatinine levels were observed in patients with a Mehran moderate risk allocated to sham group compared to the RIPC group (0.070 ± 0.16 mg/dL vs. 0.107 ± 0.13 mg/dL, p = 0.001). With regards to the primary endpoint, a significantly higher change in serum creatinine from baseline to 48-72 h was observed in the sham group compared to the RIPC group (0.023 ± 0.2 μmol/L vs -0.064 ± 0.1 μmol/L, p < 0.001). CONCLUSION RIPC as an alternative to standard therapy, improved serum creatinine levels after contrast administration in patients at risk of CIN. However, present data indicate that RIPC might have beneficial effects in patients with a moderate or high risk of CIN.
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Lower limb ischemic preconditioning combined with dietary nitrate supplementation does not influence time-trial performance in well-trained cyclists.
McIlvenna, LC, Muggeridge, DJ, Forrest Nee Whyte, LJ, Monaghan, C, Liddle, L, Burleigh, MC, Sculthorpe, N, Fernandez, BO, Feelisch, M, Easton, C
Journal of science and medicine in sport. 2019;(7):852-857
Abstract
OBJECTIVES Dietary nitrate (NO3-) supplementation and ischaemic preconditioning (IPC) can independently improve exercise performance. The purpose of this study was to explore whether NO3- supplementation, ingested prior to an IPC protocol, could synergistically enhance parameters of exercise. DESIGN Double-blind randomized crossover trial. METHODS Ten competitive male cyclists (age 34±6years, body mass 78.9±4.9kg, V⋅O2peak 55±4 mLkgmin-1) completed an incremental exercise test followed by three cycling trials comprising a square-wave submaximal component and a 16.1km time-trial. Oxygen uptake (V⋅O2) and muscle oxygenation kinetics were measured throughout. The baseline (BASE) trial was conducted without any dietary intervention or IPC. In the remaining two trials, participants received 3×5min bouts of lower limb bilateral IPC prior to exercise. Participants ingested NO3--rich gel (NIT+IPC) 90min prior to testing in one trial and a low NO3- placebo in the other (PLA+IPC). Plasma NO3- and nitrite (NO2-) were measured immediately before and after application of IPC. RESULTS Plasma [NO3-] and [NO2-] were higher before and after IPC in NIT+IPC compared to BASE (P<0.001) but did not differ between BASE and PLA+IPC. There were no differences in V⋅O2 kinetics or muscle oxygenation parameters between trials (all P>0.4). Performance in the time-trial was similar between trials (BASE 1343±72s, PLA+IPC 1350±75s, NIT+IPC 1346±83s, P=0.98). CONCLUSIONS Pre-exercise IPC did not improve sub-maximal exercise or performance measures, either alone or in combination with dietary NO3- supplementation.
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Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study.
Maxwell, JD, Carter, HH, Hellsten, Y, Miller, GD, Sprung, VS, Cuthbertson, DJ, Thijssen, DHJ, Jones, H
European journal of endocrinology. 2019;(6):659-669
Abstract
BACKGROUND Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. METHODS Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. RESULTS For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (-0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P < 0.05) between-group difference in a randomised controlled trial. CONCLUSION We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM.
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Remote ischemic preconditioning to reduce contrast-induced acute kidney injury in chronic kidney disease: a randomized controlled trial.
Ghaemian, A, Yazdani, J, Azizi, S, Farsavian, AA, Nabati, M, Malekrah, A, Dabirian, M, Espahbodi, F, Mirjani, B, Mohsenipouya, H, et al
BMC nephrology. 2018;(1):373
Abstract
BACKGROUND The impact of contrast-induced acute kidney injury (CI-AKI) on patients with chronic renal disease is well-known. Remote ischemic preconditioning (RIPC) is a non-invasive method that can reduce the risk of CI-AKI, but studies on RIPC have had different results. The aim of the present study was to assess the potential impact of RIPC on CI-AKI. METHODS In a randomized, double blinded, controlled trial, 132 patients with chronic renal dysfunction (glomerular filtration rate < 60 mL/min/m2) who underwent coronary angiography or angioplasty received adequate hydration. RIPC was performed in 66 patients by applying an upper arm blood pressure cuff. The cuff was inflated four times for 5 min to 50 mmHg above the systolic blood pressure, followed by deflation for 5 min. In the control group, the blood pressure cuff was inflated only to 10 mmHg below the patient's diastolic blood pressure. The primary endpoint was an increase in serum cystatin C ≥ 10% from baseline to 48-72 h after exposure to the contrast. RESULTS The primary endpoint was achieved in 48 (36.4%) patients (24 in each group). RIPC did not show any significant effect on the occurrence of the primary endpoint (P = 1). In addition, when the results were analyzed based on the Mehran risk score for subgroups of patients, RIPC did not reduce the occurrence of the primary endpoint (P = 0.97). CONCLUSIONS In patients at moderate-to-high risk of developing CI-AKI when an adequate hydration protocol is performed, RIPC does not have an additive effect to prevent the occurrence of CI-AKI. TRIAL REGISTRATION The clinical trial was registered on (Identification number IRCT2016050222935N2 , on December 19, 2016 as a retrospective IRCT).
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Remote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized controlled crossover pilot study.
Nair, A, Khan, S, Omar, S, Pei, XQ, McNeill, K, Chowienczyk, P, Webb, AJ
British journal of clinical pharmacology. 2017;(7):1416-1423
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Abstract
AIM: The aim of this article is to test the hypothesis that remote ischaemic preconditioning (RIPC) increases circulating endogenous local and systemic plasma (nitrite) during RIPC and ischaemia-reperfusion (IR) as a potential protective mechanism against ischaemia-reperfusion injury (IRI). METHODS Six healthy male volunteers (mean age 29.5 ± 7.6 years) were randomized in a crossover study to initially receive either RIPC (4 × 5 min cycles) to the left arm, or no RIPC (control), both followed by an ischaemia-reperfusion (IR) sequence (20 min cuff inflation to 200 mmHg, 20 min reperfusion) to the right arm. The volunteers returned at least 7 days later for the alternate intervention. The primary outcome was the effect of RIPC vs. control on local and systemic plasma (nitrite). RESULTS RIPC did not significantly change plasma (nitrite) in either the left or the right arm during the RIPC sequence. However, compared to control, RIPC decreased plasma (nitrite) during the subsequent IR sequence by ~26% (from 118 ± 9 to 87 ± 5 nmol l-1 ) locally in the left arm (P = 0.008) overall, with an independent effect of -58.70 nmol l-1 (95% confidence intervals -116.1 to -1.33) at 15 min reperfusion, and by ~24% (from 109 ± 9 to 83 ± 7 nmol l-1 ) systemically in the right arm (P = 0.03). CONCLUSIONS RIPC had no effect on plasma (nitrite) during the RIPC sequence, but instead decreased plasma (nitrite) by ~25% during IR. This would likely counteract the protective mechanisms of RIPC, and contribute to RIPC's lack of efficacy, as observed in recent clinical trials. A combined approach of RIPC with nitrite administration may be required.
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Nephroprotective effects of remote ischemic preconditioning in coronary angiography.
Zagidullin, NS, Dunayeva, AR, Plechev, VV, Gilmanov, AZ, Zagidullin, SZ, Er, F, Pavlov, VN
Clinical hemorheology and microcirculation. 2017;(3):299-307
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is a formidable side effect of iodinated contrast medium use in subjects undergoing coronary angiogram (CAG). Remote ischemic preconditioning (RIPC) may reduce the risk of CIN. AIM: The aim of the study was to investigate the nephroprotective effects of RIPC in coronary heart disease (CHD) in patients, undergoing CAG, with mild to moderate lowered estimated glomerular filtration rate (eGFR). MATERIALS In the randomized, blinded, sham RIPC (sRIPC) controlled study 51 patients with CHD and GFR less than 80 mL/min/m2, undergoing CAG, were investigated. The patients were randomized for RIPC (n = 26, 60.5±2.0 years) or sRIPC (n = 25, 62.96±1.7). RIPC was performed before the CAG by means of 3-5-minute cycle cuff pumped on the upper arm + 50 mm Hg above the systolic blood pressure (BP), while in sRIPC it corresponded to diastolic BP. The primary endpoint was the development of CIN and secondary - change of biomarkers (creatinine, urea, neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C). RESULTS In RIPC group, CIN occurred in 28% of cases, while in sRIPC - 3.8%. All investigated markers increased in sRIPC and declined in RIPC; the difference was significant in markers between the groups before and after CAG. CONCLUSIONS RIPC proved nephroprotective effect in prevention of contrast-induced nephropathy in CHD subjects with mild to moderate lowered eGFR.