Introduction
Athletes and coaches explore a variety of methods to improve athletic performance, in hopes of becoming champions in their discipline (27). Some sports-enhancing substances or techniques are banned from many federations and Olympic committees (23). Remote ischemic preconditioning (RIPC) using a pressure cuff was recently investigated on healthy participants to observe the potential benefits of this methodology in sports performance (1,4,6,7,14). For example, De Groot et al. (7) concluded that RICP increases both
;)
and muscular power in an aerobic incremental maximal ergometer incremental test. Crisafulli et al. (6) found that RIPC caused a significant improvement in maximal wattage output without increasing
, and hypothesized that the enhancement of the performance was the result of an improvement in the subject's anaerobic capacity. Jean-St-Michel et al. (14) observed an increase in performance times in university swimmers. Performance was measured as the time to complete a 100- to 200-m swim for which the participants chose their best swimming style. Bailey et al. (1) used RIPC to assess its effect on a 5-km running trial. In contrast, Clevidence et al. (4) did not report any improvement in submaximal cycling performance. All of the studies listed above explored the direct effect of RIPC on aerobic sports without exploring the potential physiological mechanisms of the intervention.
Remote ischemic preconditioning was first described as a transient ischemia of 1 coronary artery territory that reduces the effect of a potentially lethal ischemia in the territory of another coronary artery (20). The same phenomenon is observed with remote organs (kidney and intestine) to induce myocardial protection (10,17). The skeletal muscle or transient limb ischemia (arms or legs) could also trigger the same protection to the heart (15). The RIPC model is mainly studied in surgical intervention of the heart or in transplantation (18). Remote ischemic preconditioning with limb ischemia can be described as a noninvasive intervention of 4 cycles of 5-minute occlusions, followed by 5 minutes of reperfusion. The potential benefit of RIPC in sport is to let adenosine successfully reach the mitochondria, commonly referred to as a “window of protection.” The first window of protection occurs 10–60 minutes after RIPC, and the second window of protection (SWOP) occurs 24–96 hours after (30). Remote ischemic preconditioning is known to open K-ATP channels in the mitochondria by the release of adenosine (8,25,29,31). If RIPC helps patients in ischemic condition (anaerobic condition) to improve heart metabolism, we may speculate that the effect could allow a healthy subject to improve this metabolic pathway. Anaerobic exercise such as a 6-second sprint or 30-second sprints is associated with a rise of venous lactate, a fall of arterial pH, and a cause of fatigue in all types of muscles (13).
Based on Crisaffulli's suggestion about the effect of RIPC on the anaerobic system, we hypothesize that RIPC may modify the tolerance to hypoxia during anaerobic exercise and therefore enhance temporary performance of short duration (6). The aim of our study was to identify the potential benefit of RIPC on the entire lactic and alactic anaerobic systems by using specific tests for both systems (28).
As a noninvasive method, it has never been reported how patients or athletes tolerate the cycles of ischemia-reperfusion, except the fact that RIPC is well tolerated (6). Our secondary goal was to quantify on a pain scale how the subject feels when the RIPC method is used. If the results are conclusive, we want to know if the method could be tolerated by athletes.
Methods
Experimental Approach to the Problem
The hypothesis was tested with a single-blind, crossover, randomized control trial. Randomization of participants to RIPC and a SHAM intervention was computer designed (22). In our design, one of the limitations is not really double blind, and the “sham” condition is easily detectable by the subject. Each participant randomly picked a number from 1 to 17 for allocation to RIPC or the SHAM intervention in a crossover design. The RIPC intervention consisted of four 5-minute cycles of ischemia, with a pressure cuff (a large suntech medical cuff) inflated at 50 mm Hg above systolic blood pressure on the right arm, followed by 5 minutes of reperfusion. The SHAM intervention consisted of four 5-minute cycles of cuff insufflation at 10 mm Hg followed by 5 minutes of reperfusion. We counterbalanced the order of the 2 interventions with 1 week given between interventions to eliminate the potential effects of the SWOP. Participants were instructed to avoid high-intensity training (more than 7.5 metabolic units [METS], or more than 26.5 ml/O2/kg, or anaerobic intervals or strength training) during the week between tests. The experimental design is presented in Figure 1.
Figure 1: Flowchart depicting the randomization of participants.
Subjects
The ethics committee, Comité d'éthique de la recherche en santé (CERES) of the University of Montréal approved the project (certificate number: 12-048-CERES-D). Based on the sample sizes used in similar studies, a total of 15 participants were required to detect a significant difference on the exercise parameters selected for the study (6,7,14). Participants were healthy students from the University of Montréal's Department of Kinesiology and amateur triathletes affiliated to triathlon clubs (registered by Triathlon Québec). All subjects were engaged in a regular training routine. The inclusion criteria required that participants be healthy men and women between 18 and 40 years old, without any diagnosed diseases. The exclusion criteria were as follows: type 1 or 2 diabetes, high blood pressure (higher than 145/85 mm Hg at rest), heart failure, angina, aortic stenosis, acute aortic dissection, myocardial infarct, kidney failure, asthma, cancer, chronic obstructive pulmonary diseases, metabolic syndrome, hypercholesterolemia, hepatic infection, general infection, or physical handicap. The characteristics of the participants are described in Table 1. Written, informed consent was reviewed and signed by the participants before entering the study.
Table 1: Characteristics of the included participants.*
Exercise Tests
Alactic Anaerobic Test
The alactic anaerobic test was performed on an electromagnetic cycle ergometer (Excalibur; Lode BV, Groningen, Netherlands) and piloted with the Wingate computer program (Wingate Software V1, 2003; Lode BV). Participants were allowed to use either SPD-type pedals or running shoes. Warm-up is important before attending anaerobic testing to maximize the performance (23). Participants began with a warm-up of 8 minutes, at a power output of 100 W (100 rpm), followed by three 3-second sprints (a 50-second active rest between sprints). The test itself consists of six 6-second sets at: 0.9, 1.0, 1.1, 1.2, 1.3, and 1.4 Nm·kg−1 of body weight (12). Between each 6-second test, participants were allowed 2 minutes of active recovery at a low intensity followed by 3 minutes of passive rest, during which time they were allowed to drink water. The same recovery period was provided before starting the Wingate test. During each bout of testing, standardized verbal encouragement was provided by the examiner. The choice of this exercise protocol is to represent an exercise of less than 10 seconds that reflect the alactic anaerobic system.
The Wingate Test
The most accurate and reliable exercise protocol to assess maximal power and anaerobic power is the Wingate protocol (2,3,16,26,32). The Wingate protocol, which lasts for 30 seconds, is used to assess the lactic anaerobic system. The Wingate test is a 30-second maximal sprint at 0.8 Nm·kg−1 body weight for men and 0.77 Nm·kg−1 body weight for women (9).
Data of the 2 Exercises Protocol
The main data of both tests are the mean watts (in Watt). The other data of the tests are peak power (in watt), fatigue index (in watt per second), time to get to peak power (in seconds), minimal power (in watt), ratio between weight and relative mean power (in watt per kilogram), consistency (in watt per kilogram) and perceived effort on Borg scale (from 1 to 10) (9).
Pain Scale for Ischemic Preconditioning Intervention
We also asked the participants how they perceived the pain produced by ischemic preconditioning on a scale of 1–10.
Statistical Analyses
Fifteen participants were required to detect a significant difference of 10% for the comparison “control vs. intervention” in a crossover design (each participant serving as his own control), assuming a significance level of 5%, a power of 80%, and an intraclass correlation of 50%. The number of participants was increased by 10% (17) to compensate for attrition. For qualitative parameters, the population size (N for sample size and n for available data) and the percentage (of available data) for each class of parameters are presented. Quantitative parameters are summarized by the population size (N for sample size and n for available data), the mean, the SD, the median, the minimum, and the maximum values. Statistical inference was performed on all parameters without adjusting for multiplicity. Significance tests (2-sided) were performed using α = 0.05. The p-values are reported for all statistical tests.
Participants who dropped out were not replaced during the study but were included in the data analysis to the extent that datum are available. Computations for results were performed using the SAS Version 8.2 computer software package.
The null hypothesis is there is no difference between the RIPC and SHAM interventions. All data were submitted to a Student paired t-test. This procedure is more powerful in the case of a normal distribution, but because of the relatively small sample size (and potential statistical outliers), a sensitivity procedure (Wilcoxon signed rank test) was also applied to all parameters (5).
Results
All participants completed the SHAM and RIPC interventions except 1 candidate who was excluded from analysis because of illness on the second day of the study (n = 1). A second candidate was excluded from the analysis because of technical problems with the cranks of the bike that limited performance (n = 1). A flowchart depicting the randomization of participants is presented in Figure 1.
The Alactic Anaerobic Test Results
Remote ischemic preconditioning was not associated with an increase in peak power and the fatigue index or decreases in perceived effort (Table 2) for the best anaerobic test. Remote ischemic preconditioning did not alter any of the performance variables during the best alactic anaerobic test. See Table 2 for data and p-values.
Table 2: Results for the alactic test.*†
The Wingate Test Results
Remote ischemic preconditioning was associated with a nonsignificant increase in mean power and peak power and decreases in perceived effort. Remote ischemic preconditioning did not alter any of the performance variables during the Wingate test. See Table 3 for data and p-values.
Table 3: Results for the lactic test (Wingate).*
Transient Limb Ischemia Intervention
Participants were asked to rate their perceived pain on a scale of 1–10 after each cycle of ischemia with the pressure cuff (21). The mean perceived pain was 4.36/10 with a SD of 1.29. All the participants rated 0 out of 10 on the pain scale for the SHAM intervention. See Table 4 for data.
Table 4: Scale of pain perception for ischemic preconditioning intervention.*
Discussion
The results of this study showed no significant improvement provided by RIPC for either the anaerobic lactic test or the anaerobic alactic test. Our results are concordant with the findings of Gibson et al. (11), who demonstrated no potential benefit of RIPC on anaerobic performance in a 30-m sprint for well-trained participants. Our results are also consistent with the results of Crisafulli et al. (6), who did not report any significant changes in anaerobic performance. In the literature, De Groot et al. (7) reported significant findings in maximal power output of 1.6% (372 watts for the RIPC group and 366 watts for the SHAM group, p = 0.05) although the results are not physiologically significant (7). Our data show a similar increase in power, 794 W for the RIPC intervention vs. 776 watts for the SHAM intervention, p = 0.208. The participants in our study and in the study by De Groot et al. (7) were comparable across characteristics (well-trained healthy participants). Our data also showed a 1.6% increase in maximal power performance, but it was not a statistically significant finding. Crisafulli et al. (6) reported a significant increase in power: 278 watts for the SHAM group vs. 290 watts for the RIPC group. The range of increases in power is consistent with our results. Our results are also in accord with Clevidence et al. (4), who did not conclude any significant improvement in cycling performance with RIPC. Our study includes the first protocol designed to investigate the effect of RIPC on the entire anaerobic pathway using a 6-second test and a Wingate test (the difference in power reflects the difference between a specific anaerobic test vs. an incremental aerobic test). The 6-second test was used to assess the maximal capacity of the ATP-PC system, whereas the Wingate test measured both the ATP-CP system and anaerobic glycolysis. Our data clearly demonstrate that RIPC and SHAM interventions have similar outcomes, namely that the ATP-CP system may not respond to RIPC. With our findings and the results of the literature, we can speculate that RIPC may have potential benefit on aerobic-based performance.
To our knowledge, this is the first study to assess the effect of transient limb ischemia using a pain scale. Our participants reported a rating of perceived pain of 4.36/10 after four 5-minute cycles of ischemia. The participants assigned to the SHAM intervention reported a 0/10 on the pain scale. This suggests that the intervention is tolerable for the participants. If the effect of RIPC was significant, many participants reported that they would use the technique despite the pain. It is also interesting to note that 59% of the participants thought that RIPC would enhance their performance.
Our data show that there is no placebo effect of RIPC. Therefore, one limitation of this study was that we could not realistically conduct a double-blind examination because the SHAM intervention induced no perceived pain to render the conditions indistinguishable. Given that an effect of RIPC on performance might be related to the training status of the subjects (4), the use of a heterogeneous population (students and amateur triathletes) in this study could be problematic even if both of them are healthy, well-trained subjects.
Practical Applications
This study provides insight for the coaches who want to use RIPC as a sport enhancement method. Although it was established in previous studies that RIPC could improve some sport performance, none of them assessed the direct effect of this method on the anaerobic system. Our findings provide no significant improvement on short, intense exercise (30 seconds and less) on healthy subjects. Even if RIPC could be well tolerated by the subjects because of a low scoring on the pain scale, we do not recommend the use of RICP before short-term exercise for now. Further studies could possibly demonstrate a potential benefit on aerobic exercise (19).
Acknowledgments
This project has no funding sources. No companies or manufacturers will benefit from the results of the present study. There is no conflict of interest involved in this study.
References
1. Bailey TG, Jones H, Gregson W, Atkinson G, Cable NT, Thijssen DH. Effect of ischemic preconditioning on lactate accumulation and running
performance. Med Sci Sports Exerc 44: 2084–2089, 2012.
2. Bar-Or O. The
Wingate anaerobic test. An update on methodology, reliability and validity. Sports Med 4: 381–394, 1987.
3. Barfield JP, Sells PD, Rowe DA, Hannigan-Downs K. Practice effect of the
Wingate anaerobic test. J Strength Cond Res 16: 472–473, 2002.
4. Clevidence MW, Mowery RE, Kushnick MR. The effects of ischemic preconditioning on aerobic and anaerobic variables associated with submaximal
cycling performance. Eur J Appl Physiol 112: 3649–3654, 2012.
5. Cohen J. Statistical Power Analysis for the Behavioral Sciences (2nd ed.). Hillsdale, NJ: Lawrence Erlbaum Associates, 1988. pp. 19–66.
6. Crisafulli A, Tangianu F, Tocco F, Concu A, Mameli O, Mulliri G, Caria MA. Ischemic preconditioning of the muscle improves maximal
exercise performance but not maximal oxygen uptake in humans. J Appl Physiol (1985) 111: 530–536, 2011.
7. De Groot PC, Thijssen DH, Sanchez M, Ellenkamp R, Hopman MT. Ischemic preconditioning improves maximal
performance in humans. Eur J Appl Physiol 108: 141–146, 2010.
8. Dos Santos P, Kowaltowski AJ, Laclau MN, Seetharaman S, Paucek P, Boudina S, Garlid KD. Mechanisms by which opening the mitochondrial ATP-sensitive K(+) channel protects the ischemic heart. Am J Physiol Heart Circ Physiol 283: H284–H295, 2002.
9. Gastin P, Lawson D, Hargreaves M, Carey M, Fairweather I. Variable resistance loadings in anaerobic power testing. Int J Sports Med 12: 513–518, 1991.
10. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD. Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94: 2193–2200, 1996.
11. Gibson N, White J, Neish M, Murray A. Effect of ischemic preconditioning on land-based sprinting in team-sport athletes. Int J Sports Physiol Perform 8: 671–676, 2013.
12. Gouadec K. Measuring the Anaerobic Capacity Using an Isokinetic Dynamometer. Montreal, Canada: University of Montreal Press, 2008.
13. Hargreaves M, McKenna MJ, Jenkins DG, Warmington SA, Li JL, Snow RJ, Febbraio MA. Muscle metabolites and
performance during high-intensity, intermittent
exercise. J Appl Physiol (1985) 84: 1687–1691, 1998.
14. Jean-St-Michel E, Manlhiot C, Li J, Tropak M, Michelsen MM, Schmidt MR, Redington AN. Remote preconditioning improves maximal
performance in highly-trained athletes. Med Sci Sports Exerc 43: 1280–1286, 2011.
15. Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, MacAllister R. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106: 2881–2883, 2002.
16. Maud PJ, Shultz BB. Norms for the
Wingate anaerobic test with comparison to another similar test. Res Q Exerc Sport 60: 144–151, 1996.
17. Pell TJ, Baxter GF, Yellon DM, Drew GM. Renal ischemia preconditions myocardium: Role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol 275: H1542–H1547, 1998.
18. Pilcher JM, Young P, Weatherall M, Rahman I, Bonser RS, Beasley RW. A systematic review and meta-analysis of the cardioprotective effects of remote ischaemic preconditioning in open cardiac surgery. J R Soc Med 105: 436–445, 2012.
19. Popov DV, Vinogradova OL. Aerobic
performance: Role of oxygen delivery and utilization, glycolytic flux [in Russian]. Usp Fiziol Nauk 43: 30–47, 2012.
20. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic “preconditioning” protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87: 893–899, 1993.
21. Puntillo KA, White C, Morris AB, Perdue ST, Stanik-Hutt J, Thompson CL, Wild LR. Patients' perceptions and responses to procedural pain: Results from Thunder project II. Am J Crit Care 10: 238–251, 2001.
22. Saghaei M. Random allocation software for parallel group randomized trials. BMC Med Res Methodol 4: 26, 2004.
23. Souissi N, Driss T, Chamari K, Vandewalle H, Davenne D, Gam A, Jousselin E. Diurnal variation in
wingate test performances: Influence of active warm-up. Chronobiol Int 27: 640–652, 2010.
24. Thevis M, Kuuranne T, Geyer H, Schanzer W. Annual banned-substance review: Analytical approaches in human sports drug testing. Drug Test Anal 4: 164–184, 2012.
25. Vander Heide RS, Hill ML, Reimer KA, Jennings RB. Effect of reversible ischemia on the activity of the mitochondrial ATPase: Relationship to ischemic preconditioning. J Mol Cell Cardiol 28: 103–112, 1996.
26. Vandewalle H, Peres G, Monod H. Standard anaerobic
exercise tests. Sports Med 4: 268–289, 1987.
27. Wang D. Understanding
performance-enhancing drug use. Conn Med 76: 487–491, 2012.
28. Wells GD, Selvadurai H, Tein I. Bioenergetic provision of energy for muscular activity. Paediatr Respir Rev 10: 83–90, 2009.
29. Wolfrum S, Schneider K, Heidbreder M, Nienstedt J, Dominiak P, Dendorfer A. Remote preconditioning protects the heart by activating myocardial PKCepsilon-isoform. Cardiovasc Res 55: 583–589, 2002.
30. Yellon DM, Downey JM. Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiol Rev 83: 1113–1151, 2003.
31. Zingman LV, Alekseev AE, Hodgson-Zingman DM, Terzic A. ATP-sensitive potassium channels: Metabolic sensing and cardioprotection. J Appl Physiol (1985) 103: 1888–1893, 2007.
32. Zupan MF, Arata AW, Dawson LH, Wile AL, Payn TL, Hannon ME.
Wingate anaerobic test peak power and anaerobic capacity classifications for men and women intercollegiate athletes. J Strength Cond Res 23: 2598–2604, 2009.
