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1.
Remote ischemic conditioning for acute respiratory distress syndrome in COVID-19.
Incognito, AV, Millar, PJ, Pyle, WG
American journal of physiology. Lung cellular and molecular physiology. 2021;(3):L331-L338
Abstract
Acute respiratory distress syndrome and subsequent respiratory failure remains the leading cause of death (>80%) in patients severely impacted by COVID-19. The lack of clinically effective therapies for COVID-19 calls for the consideration of novel adjunct therapeutic approaches. Though novel antiviral treatments and vaccination hold promise in control and prevention of early disease, it is noteworthy that in severe cases of COVID-19, addressing "run-away" inflammatory cascades are likely more relevant for improvement of clinical outcomes. Viral loads may decrease in severe, end-stage coronavirus cases, but a systemically damaging cytokine storm persists and mediates multiple organ injury. Remote ischemic conditioning (RIC) of the limbs has shown potential in recent years to protect the lungs and other organs against pathological conditions similar to that observed in COVID-19. We review the efficacy of RIC in protecting the lungs against acute injury and current points of consideration. The beneficial effects of RIC on lung injury along with other related cardiovascular complications are discussed, as are the limitations presented by sex and aging. This adjunct therapy is highly feasible, noninvasive, and proven to be safe in clinical conditions. If proven effective in clinical trials for acute respiratory distress syndrome and COVID-19, application in the clinical setting could be immediately implemented to improve outcomes.
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2.
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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3.
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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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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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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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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Limb Ischemic Conditioning Induces Oxidative Stress Followed by a Correlated Increase of HIF-1α in Healthy Volunteers.
García-de-la-Asunción, J, Perez-Griera, J, Moreno, T, Duca, A, García-Del-Olmo, N, Belda, J, Soro, M
Annals of vascular surgery. 2020;:412-419
Abstract
BACKGROUND Local and remote ischemic preconditioning has been used as a protective intervention against ischemia/reperfusion (I/R) damage in several preclinical and clinical studies. However, its physiological mechanisms are not completely known. I/R increases the production of reactive oxygen species, which also serve as messengers for a variety of functions. Hypoxia-inducible factor 1 alpha (HIF-1α) is probably the most important transcription factor mediator of hypoxic signaling. OBJECTIVE We hypothesized that limb ischemic conditioning (LIC) induces a local oxidative/nitrosative stress and a correlated increase of HIF-1α plasma levels. METHODS An observational, prospective, and single-center study has been conducted in 27 healthy volunteers. LIC was applied: three cycles (5 min of ischemia followed by 5 min of reperfusion) using an ischemia cuff placed on the upper left arm. Time course of 8-isoprostane, nitrite, and HIF-1α levels was measured in blood plasma. Venous blood was sampled from the left arm before tourniquet inflation (basal) and after LIC: 1 min and 2 hr for 8-isoprostane and nitrite; and 1 min, 2 hr, 8 hr, 24 hr, and 48 hr for HIF-1α. RESULTS After LIC, we have found an early increase of 8-isoprostane and nitrite. HIF-1α increased at 2 and 8 hr after LIC. We found a direct correlation between HIF-1α and 8-isoprostane and nitrite plasma levels. CONCLUSIONS We concluded that LIC induces an early oxidative/nitrosative stress in the arm followed by an increase of HIF-1α plasma levels correlated with 8-isoprostane and nitrite levels, possibly as a local response.
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8.
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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Opioids Preconditioning Upon Renal Function and Ischemia-Reperfusion Injury: A Narrative Review.
Palomino, J, Echavarria, R, Franco-Acevedo, A, Moreno-Carranza, B, Melo, Z
Medicina (Kaunas, Lithuania). 2019;(9)
Abstract
Kidneys have an important role in regulating water volume, blood pressure, secretion of hormones and acid-base and electrolyte balance. Kidney dysfunction derived from acute injury can, under certain conditions, progress to chronic kidney disease. In the late stages of kidney disease, treatment is limited to replacement therapy: Dialysis and transplantation. After renal transplant, grafts suffer from activation of immune cells and generation of oxidant molecules. Anesthetic preconditioning has emerged as a promising strategy to ameliorate ischemia reperfusion injury. This review compiles some significant aspects of renal physiology and discusses current understanding of the effects of anesthetic preconditioning upon renal function and ischemia reperfusion injury, focusing on opioids and its properties ameliorating renal injury. According to the available evidence, opioid preconditioning appears to reduce inflammation and reactive oxygen species generation after ischemia reperfusion. Therefore, opioid preconditioning represents a promising strategy to reduce renal ischemia reperfusion injury and, its application on current clinical practice could be beneficial in events such as acute renal injury and kidney transplantation.