Ischemic preconditioning delays the time of exhaustion in cycling performance during the early but not in the late phase

Endothelial progenitor cells (EPCs) have been shown to participate in tissue repair under diverse physiological and pathological conditions. It is unknown whether EPCs are mobilized in response to acute renal injury. The aim of this study was to characterize EPC mobilization and homing in the course of acute renal ischemia. Mice were subjected to unilateral renal artery clamping (UC) for 25 min. At 10 min, 3, 6, 24 h, and 7 days after UC, the pool of circulating and splenic CD34+/Flk-1+ cells within the monocytic population was detected by flow cytometry. For ischemic preconditioning (IPC), the first UC was performed 7 days before the repeated ischemic episode. For EPC detection in the kidney, cryosections were stained for c-Kit+/Tie-2+ cells. The number of circulating EPCs was not significantly affected at any time after UC compared with sham-operated or control mice. IPC did not significantly change the circulating pool of EPCs. Splenectomy performed before UC resulted in a surge of circulating EPCs. Accordingly, splenic EPCs were significantly increased after UC at 3 and 6 h, but not at later times. EPC homing to the spleen was absent in IPC animals. Immunohistochemical analysis of the kidneys showed a sixfold increase in the number of c-Kit+/Tie-2+ cells localized in the medullopapillary region in mice by day 7 after ischemia. Enriched population of c-Kit+/Tie-2+ cells from the medullopapillary parenchyma of Tie-2green fluorescent protein chimeric mice subjected to IPC was isolated and transplanted to wild-type mice with acute renal ischemia. This procedure resulted in the improvement of renal function in recipients. In conclusion, 1) renal ischemia rapidly (within 3–6 h) mobilizes EPCs, which transiently home to the spleen, acting as a temporary reservoir of mobilized EPCs; 2) the late phase of IPC is associated with the mobilization of the splenic pool and accumulation of EPCs in the renal medullopapillary region; and 3) transplantation of EPC-enriched cells from the medullopapillary parenchyma afforded partial renoprotection after renal ischemia, suggesting the role of the recruited EPCs in the functional rescue.

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Ischemic Preconditioning: Improved Cycling Performance Despite Nocebo Expectation

International Journal of Sports Physiology and Performance ◽

10.1123/ijspp.2019-0290 ◽

2020 ◽

Vol 15 (3) ◽

pp. 354-360 ◽

Cited By ~ 1

Author(s):

Christian P. Cheung ◽

Joshua T. Slysz ◽

Jamie F. Burr

Keyword(s):

Ischemic Preconditioning ◽

Aerobic Power ◽

Lactate Concentration ◽

Cycling Performance ◽

Cycle Ergometer ◽

Time To Exhaustion ◽

Performance Expectations ◽

Sham Treatment ◽

Positive Expectation ◽

Placebo Controls

Purpose: Ischemic preconditioning (IPC) through purposeful circulatory occlusion may enhance exercise performance. The value of IPC for improving performance is controversial owing to challenges with employing effective placebo controls. This study examines the efficacy of IPC versus a deceptive sham protocol for improving performance to determine whether benefits of IPC are attributable to true physiological effects. It was hypothesized that IPC would favorably alter performance more than a sham treatment and that physiological responses to exercise would be affected only after IPC treatment. Methods: In a randomized order, 16 participants performed incremental exercise to exhaustion on a cycle ergometer in control conditions and after sham and IPC treatments. Participants rated their belief as to the efficacy of each treatment compared with control. Results: Time to exhaustion was greatest after IPC (control = 1331 [270] s, IPC = 1429 [300] s, sham = 1343 [255] s, P = .02), despite negative performance expectations after IPC and positive expectation after sham. Maximal aerobic power remained unchanged after both SHAM and IPC (control = 42.0 [5.2], IPC = 41.7 [5.5], sham = 41.6 [5.5] mL·kg−1·min−1, P = .7), as did submaximal lactate concentration (control = 8.9 [2.6], sham = 8.0 [1.9], IPC = 7.7 [2.1] mmol, P = .1) and oxygen uptake (control = 37.8 [4.8], sham = 37.5 [5.3], IPC = 37.5 [5.5] mL·kg−1·min−1, P = .6). Conclusions: IPC before cycling exercise provides an ergogenic benefit that is not attributable to a placebo effect from positive expectation and that was not explained by traditionally suggested mechanisms.

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Abstract 3313: Smoking Abolishes Ischemic Preconditioning-Induced Augmentation of Endothelium-Dependent Vasodilation: Role of Endothelium-Derived Nitric Oxide and Circulating Endothelial Progenitor Cells

Circulation ◽

10.1161/circ.116.suppl_16.ii_746-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Yukihito Higashi ◽

Masashi Kimura ◽

Chikara Goto ◽

Daisuke Jitsuiki ◽

Kenji Nishioka ◽

...

Keyword(s):

Nitric Oxide ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Ischemic Preconditioning ◽

Late Effects ◽

Late Phase ◽

Limb Ischemia ◽

No Production ◽

Endothelial Progenitor ◽

Before And After

Background: Several studies have shown that both early and late effects of ischemic preconditioning (IPC) protect against myocardial injury following ischemic reperfusion. Recently, we have shown that repetition of IPC stimulus augments endothelium-dependent vasodilation in forearm circulation of healthy subjects through increases in nitric oxide (NO) production and number of endothelial progenitor cells (EPCs) under a local condition. The purpose of this study was to evaluate the late effects of IPC on endothelial function in smokers. Methods and Results: Late phase of IPC was induced by upper limb ischemia (cuff inflation of over 200 mmHg for 5 minutes) six times a day for one month. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh) and to sodium nitroprusside (SNP) before and after IPC stimulus in 15 male smokers (27±7 yr) and 15 male non-smokers (26±5 yr). FBF was measured using a strain-gauge plethysmography. The IPC stimulus significantly increased plasma concentration of vascular endothelial growth factor (VEGF) from 84.7±10.6 to 120.3±13.5 pg/mL (P<0.05), circulating level of EPCs from 1258±198 to 1608±183 cells/mL (P<0.05) and FBF responses to ACh from 17.3±4.9 to 24.8±6.9 mL/min/100 mL tissue (P<0.05) in non-smokers, but these did not change in the smoker group. The FBF responses to SNP were similar before and after the IPC stimulus. Infusion of N G -monomethyl-L-arginine, a NO synthase inhibitor, completely eliminated the IPC stimulus-induced augmentation of FBF responses to ACh in non-smokers. Conclusions: These findings suggest that repetition of IPC stimulus may be a simple, safe, and feasible therapeutic technique for endothelial protection of peripheral vessels. However, smoking abolishes repetition of IPC stimulus-induced augmentation of endothelium-dependent vasodilation.

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The late phase of ischemic preconditioning induces a prosurvival genetic program that results in marked attenuation of apoptosis

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2007.03.908 ◽

2007 ◽

Vol 42 (6) ◽

pp. 1075-1085 ◽

Cited By ~ 20

Author(s):

Adam B. Stein ◽

Roberto Bolli ◽

Yiru Guo ◽

Ou-Li Wang ◽

Wei Tan ◽

...

Keyword(s):

Ischemic Preconditioning ◽

Late Phase ◽

Genetic Program

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Effects of ischemic preconditioning on short-duration cycling performance

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0646 ◽

2016 ◽

Vol 41 (8) ◽

pp. 825-831 ◽

Cited By ~ 26

Author(s):

Rogério Santos de Oliveira Cruz ◽

Rafael Alves de Aguiar ◽

Tiago Turnes ◽

Amadeo Félix Salvador ◽

Fabrizio Caputo

Keyword(s):

Skeletal Muscle ◽

Blood Lactate ◽

Ischemic Preconditioning ◽

Power Output ◽

Muscle Activation ◽

Endurance Performance ◽

Cycling Performance ◽

Oxygen Deficit ◽

Mean Power ◽

Lactate Kinetics

It has been demonstrated that ischemic preconditioning (IPC) improves endurance performance. However, the potential benefits during anaerobic events and the mechanism(s) underlying these benefits remain unclear. Fifteen recreational cyclists were assessed to evaluate the effects of IPC of the upper thighs on anaerobic performance, skeletal muscle activation, and metabolic responses during a 60-s sprint performance. After an incremental test and a familiarization visit, subjects were randomly submitted in visits 3 and 4 to a performance protocol preceded by intermittent bilateral cuff inflation (4 × (5 min of blood flow restriction + 5 min reperfusion)) at either 220 mm Hg (IPC) or 20 mm Hg (control). To increase data reliability, each intervention was replicated, which was also in a random manner. In addition to the mean power output, the pulmonary oxygen uptake, blood lactate kinetics, and quadriceps electromyograms (EMGs) were analyzed during performance and throughout 45 min of passive recovery. After IPC, performance was improved by 2.1% compared with control (95% confidence intervals of 0.8% to 3.3%, P = 0.001), followed by increases in (i) the accumulated oxygen deficit, (ii) the amplitude of blood lactate kinetics, (iii) the total amount of oxygen consumed during recovery, and (iv) the overall EMG amplitude (P < 0.05). In addition, the ratio between EMG and power output was higher during the final third of performance after IPC (P < 0.05). These results suggest an increased skeletal muscle activation and a higher anaerobic contribution as the ultimate responses of IPC on short-term exercise performance.

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