Journal Logo

APPLIED SCIENCES

Effect of Leg Eccentric Exercise on Muscle Damage of the Elbow Flexors after Maximal Eccentric Exercise

CHEN, TREVOR C.1; CHEN, HSIN-LIAN2; CHENG, LI-FU1; CHOU, TAI-YING3; NOSAKA, KAZUNORI4

Author Information
Medicine & Science in Sports & Exercise: July 2021 - Volume 53 - Issue 7 - p 1473-1481
doi: 10.1249/MSS.0000000000002616
  • Free

Abstract

One bout of unaccustomed maximal eccentric exercise confers strong muscle damage–protective effects on the subsequent bout of the same exercise performed by the same muscle (1–6) or homologous muscle of the contralateral limb (7–12). These adaptations are referred to as the repeated bout effect, and that for the contralateral limb muscle is specifically termed as the contralateral repeated bout effect (3). The contralateral repeated bout effect has been demonstrated for the elbow flexors (EF) (4,8,10–12), knee extensors (7), and knee flexors (KF) (9). Chen et al. (8) showed that the right or left EF maximal eccentric exercise consisting of five sets of six maximal eccentric contractions (MaxEC) attenuated the magnitude of changes in indirect muscle damage markers after the second bout of EF eccentric exercise that was performed by the opposite arm at 24 h, 1 wk, or 4 wk, but not within 12 h or at 8 wk after the first exercise. It was also reported that the first eccentric exercise of the KF attenuated muscle damage after the second bout of the same exercise performed by the contralateral leg at 1 or 7 d later, but no such effect was found when the first and second bouts were separated by 4 wk (9).

These suggest that the first bout of eccentric exercise confers a muscle damage–protective effect to the homologous muscle of the contralateral limb (4,7–12), but no previous study has confirmed if this effect is limited only to homologous muscle. If one of the mechanisms underpinning the contralateral repeated bout effect is adaptations of systemic inflammation (3,13), it seems possible that the first eccentric exercise bout that induces muscle damage confers muscle damage–protective effect on subsequent eccentric bout of other muscles. It might be that a leg eccentric exercise that induced muscle damage reduces the magnitude of muscle damage of an arm eccentric exercise by adaptive immunity (13). It could be that the greater the muscle damage after a leg muscle eccentric exercise, the greater the protective effect on arm muscle damage is conferred. Moreover, it is important to examine whether such effect is different between ipsilateral (e.g., left leg and left arm) and contralateral sides (e.g., right leg and left arm).

The present study tested the hypotheses that the initial bout of knee extensor or KF maximal eccentric exercise would attenuate the extent of muscle damage induced by the subsequent bout of maximal eccentric exercise of the EF, but the ipsilateral and contralateral sides of the leg exercise would not confer the protective effect on muscle damage by the EF eccentric exercise differently. Because the extent of muscle damage was reported to be greater after eccentric exercise of the KF than the knee extensors (14), it was assumed that the KF eccentric exercise would confer a greater muscle damage–protective effect than the knee extensor eccentric exercise on the EF eccentric exercise. The second hypothesis was based on the previous studies (8,15) showing that the magnitude of muscle damage induced by maximal eccentric exercise of the EF was similar between right and left, or dominant and nondominant arms. In addition, the magnitude of muscle damage induced by maximal eccentric exercise of the knee extensors (2) or flexors (9) was shown to be similar between right and left legs. Thus, if adaptive immunity (13) is responsible for the protective mechanisms, no significant differences would be observed between the ipsilateral (e.g., left leg and left arm) and contralateral sides (e.g., right leg and left arm).

If any effects of the leg exercises on the EF eccentric exercise exist, it would be detected by smaller changes in maximal voluntary concentric contraction torque, range of motion (ROM), muscle soreness, and plasma creatine kinase (CK) activity after the EF eccentric exercise, when compared with the changes after the exercise that is performed without a leg exercise. The results of the present study will shed light on the mechanisms underpinning the repeated bout effect.

METHODS

Study Design

Sixty-five young sedentary healthy men who had no musculoskeletal injuries of the upper and lower extremities were recruited for this study. They provided informed consent to participate in the study that had been approved by the Research Ethic Committee of National Taiwan Normal University (Taiwan). The study was conducted in conformity with the policy statement regarding the use of human participants by the Medicine & Science in Sports & Exercise® and Declaration of Helsinki. Their mean (±SD) age, height, body mass, and maximal voluntary isokinetic (60°·s−1) concentric contraction (MVC) torque of the EF (nondominant arm) were 22.0 ± 1.9 yr, 173.5 ± 5.6 cm, and 67.3 ± 10.3 kg, and 31.0 ± 3.6 N·m, respectively.

The sample size was estimated using the data from our previous study in which the contralateral repeated bout effect of the EF was investigated (8). Based on the possible effect size of 1 for a difference in some muscle damage marker changes between the first and second bouts, with an α level of 0.05, and a power (1 − β) of 0.80 (16), it was estimated that at least 12 participants were necessary per group. Considering a possible estimation error, 13 participants were recruited for each group.

The participants were placed in one of the five groups (n = 13 per group) by matching the baseline MVC torque among the groups as much as possible: one control group and four experimental groups. The participants in the control group (all of them were right-arm dominant based on the arm they would use to throw a ball) performed the first and second bouts of MaxEC of the EF using their right or left arm for the first bout and left or right arm for the second bout in a counterbalanced fashion (EF–EF). Although no significant differences between right and left, or dominant and nondominant arms for their responses to maximal eccentric exercise of the EF were reported (8,15), six participants in the control group used their right arms and other seven participants used their left arms for the first bout. Which arm would be used for the first bout was determined by a lottery, after placing the 13 participants to seven subgroups based on their EF MVC torque from the highest to the lowest (1–13). From the lottery result, one participant in each group used his right (dominant) arm, and other participant used his left (nondominant) arm for the first bout. It should be noted that the number of participants who used their right (dominant) arms first was larger (n = 7) than who used their left (nondominant) arms first. However, this imbalance should not be a big issue because of similar responses between arms to the eccentric exercise of the EF as stated previously. The participants in the experimental groups performed MaxEC of the EF by the nondominant arm in the second exercise bout, but the first eccentric exercise bout was different among the groups. Two of the experimental groups performed MaxEC of the KF with ipsilateral (Ipsi-KE-EF) or contralateral side of the nondominant arm (Cont-KE-EF), and other two experimental groups performed MaxEC of the KF with ipsilateral (Ipsi-KF-EF) or contralateral side of the nondominant arm (Cont-KF-EF). The second bout of MaxEC was performed 1 wk after the first bout for all groups. No significant (P > 0.05) differences in age, height, body mass, and baseline EF MVC torque were observed among the groups.

Familiarization Session

A familiarization session was done at 3 d before the first MaxEC, in which the participants experienced measurements of muscle soreness and ROM and performed submaximal (approximately 50%) MVC torque measurements. The investigator demonstrated the MaxEC that would be performed in the first and second bouts, but no eccentric contractions of the EF, KE, or KF were performed by the participants.

Eccentric Exercises

All MaxEC (EF, KE, or KF) consisted of five sets of six MaxEC at the angular velocity of 30°·s−1 on an isokinetic dynamometer (Biodex System S4; Biodex Medical Systems, Shirley, NY). In EF MaxEC, the elbow joint was forcibly extended from 90° to a fully extended position (the elbow joint fully extended position, 0°) by the lever arm of the dynamometer (17–19). In KE MaxEC, the knee joint was forcibly flexed from 30° to a flexed position (120° of knee flexion), and in KF MaxEC, the knee joint was forcibly extended from 90° to a fully extended position (14,20). Each participant was asked to maximally resist against the elbow extending, knee flexing, and knee extending movements of the dynamometer for the EF, KE, and KF MaxEC, respectively (8,14,20). The MaxEC of the EF, KE, and KF were adopted from our previous studies; thus, the details can be found elsewhere (8,14,20). Briefly, each eccentric contraction lasted for 3 s, was repeated every 10 s, and a 2-min rest was given between sets. After each contraction, the isokinetic dynamometer passively brought the participant’s arm or leg to the starting position at the angular velocity of 9°·s−1. The peak torque and work of each contraction were calculated using a software of the Biodex Medical Systems, and their average values of each set were used for further analysis (8,14).

Dependent Variables

The dependent variables consisted of MVC torque, ROM at the elbow and knee joint, muscle soreness, and plasma CK activity. MVC torque and ROM measures were taken 2 d and immediately before, immediately after, and 1, 2, 3, 4, and 5 d after the first and second eccentric exercise bouts, and muscle soreness and plasma CK activity were measured at all time points except immediately after exercise (8,9,14). The test–retest reliability of these measures has been checked in our previous studies (8,9), and based on intraclass correlation coefficient (r) and coefficient of variation, r was greater than 0.88 (KE MVC torque: 0.92, KF MVC torque: 0.91, EF MVC torque: 0.91, ROM of the knee joint: 0.96, ROM of the elbow joint: 0.99, CK: 0.88, and muscle soreness: 1.00), and coefficient of variation is less than 9.8% (9.8%, 9.1%, 8.9%, 5.8%, 1.9%, 9.3%, and 0.0%) for the dependent variables measured in the present study.

MVC torque

MVC torque was measured by the isokinetic dynamometer in the same participant position as that described for the MaxEC, at the angular velocity of 60°·s−1 for the ROM of 120° for the EF (0°–120°) and elbow extensor (120°–0°), and KF (0°–120°) and KE (120°–0°) for three continuous contractions for both directions (14,21). Verbal encouragement was provided during the tests. The highest value of the three trials for each torque was used for further analysis (22–24).

ROM

ROM was determined as the difference in the joint angles between maximal voluntarily flexion and extension using a manual goniometer for the elbow and knee joint. Three measurements were taken for each angle, and the mean of the three measurements was used to calculate ROM (14).

Muscle soreness

Muscle soreness of the EF, KE, and KF was quantified using a visual analog scale (VAS) that had a 100-mm continuous line with “not sore at all” on one side (0 mm) and “very, very sore” on the other side (100 mm) (14,21). The investigator asked the participant to rate his perceived soreness on the VAS when the muscles were passively extended (17,25).

Plasma CK activity

Approximately 5 mL of venous blood was withdrawn by a standard venipuncture technique from the cubital fossa region, put into a vacutainer tube containing dipotassium ethylenediaminetetraacetic acid (K2EDTA; Becton Dickinson and Company, Plymouth, United Kingdom), and then centrifuged (3000 rpm) for 10 min to extract plasma, and plasma samples were stored at −80°C until analyses. Plasma CK activity was assayed spectrophotometrically by an automated clinical chemistry analyzer (Model 7080; Hitachi, Co. Ltd., Tokyo, Japan) using a commercial test kit. Each sample was analyzed in duplicate, and the average value of two measures was used for further analysis.

Statistical Analyses

Data were assessed by a Shapiro–Wilk test for the normality and a Levene test for the homogeneity of variance assumption. All dependent variables before each exercise bout were compared among the groups by one-way ANOVA. Changes in peak torque and work during EF MaxEC were compared among the groups by mixed-design, two-way ANOVA, and changes in peak torque and work during KE or KF MaxEC were compared between the ipsilateral and contralateral conditions by mixed-design, two-way ANOVA. Changes in the dependent variables after EF MaxEC were compared among the groups using mixed-design, two-way ANOVA. Changes in the dependent variables after the KF and KE MaxEC were also compared among the experimental groups by mixed-design, two-way ANOVA. When a significant interaction effect was found, a series of two-way ANOVAs were performed to compare between two groups. When the ANOVA found a significant interaction effect, Tukey’s post hoc test was performed. As a measure of effect size, η2 was calculated for each variable, and ~0.02 was considered as small effect; ~0.13, medium effect; and >0.26, large effect (26). A significant level was set at P ≤ 0.05. The data were presented as mean ± SD, unless otherwise stated. All statistical analyses were performed by the IBM SPSS Statistics 20.0 software (https://www.ibm.com/support/pages/downloading-ibm-spss-statistics-20).

RESULTS

Baseline Measures

No significant (P > 0.05) differences in any of the dependent variables except plasma CK activity existed among the groups before EF MaxEC (Figs. 1–4), and before KE MaxEC and KF MaxEC for the experimental groups (Table 1). Plasma CK activity was significantly higher before the second EF MaxEC compared with the first EF MaxEC for the control group (P = 0.021, η2 = 0.371), and the baseline value of the control group before the second MaxEC was higher than that of other groups (P < 0.001, η2 = 0.371; Fig. 4).

F1
FIGURE 1:
Normalized changes in maximal isokinetic concentric torque of the EF (MVC) before (pre), immediately after (post), and 1–5 d (1–5) after the first (CONTROL1) and second (CONTROL2) bouts of maximal eccentric exercise of the EF for the control group, and after maximal eccentric exercise of the EF for the contralateral (Cont-KE-EF) and ipsilateral (Ipsi-KE-EF) knee extensors and flexors (Cont-KF-EF, Ipsi-KF-EF) groups. Mean ± SD values of 13 subjects are shown for each group. An asterisk (*) indicates a significant difference (P < 0.05) between groups based on the interaction effect shown by the ANOVA.
F2
FIGURE 2:
Absolute changes in ROM of the elbow before (pre), immediately after (post), and 1–5 d (1–5) after the first (CONTROL1) and second (CONTROL2) bouts of maximal eccentric exercise of the EF for the control group, and after maximal eccentric exercise of the EF for the contralateral (Cont-KE-EF) and ipsilateral (Ipsi-KE-EF) knee extensors and flexors (Cont-KF-EF, Ipsi-KF-EF) groups. Mean ± SD values of 13 subjects are shown for each group. An asterisk (*) indicates a significant difference (P < 0.05) between groups based on the interaction effect shown by the ANOVA.
F3
FIGURE 3:
Changes in muscle soreness of the elbow before (pre) and 1–5 d (1–5) after the first (CONTROL1) and second (CONTROL2) bouts of maximal eccentric exercise of the EF for the control group, and after maximal eccentric exercise of the EF for the contralateral (Cont-KE-EF) and ipsilateral (Ipsi-KE-EF) knee extensors and flexors (Cont-KF-EF, Ipsi-KF-EF) groups. Mean ± SD values of 13 subjects are shown for each group. An asterisk (*) indicates a significant difference (P < 0.05) between groups based on the interaction effect shown by the ANOVA.
F4
FIGURE 4:
Changes in plasma CK activity of the elbow before (pre) and 1–5 d (1–5) after the first (CONTROL1) and second (CONTROL2) bouts of maximal eccentric exercise of the EF for the control group, and after maximal eccentric exercise of the EF for the contralateral (Cont-KE-EF) and ipsilateral (Ipsi-KE-EF) knee extensors and flexors (Cont-KF-EF, Ipsi-KF-EF) groups. Mean ± SD values of 13 subjects are shown for each group. An asterisk (*) indicates a significant difference (P < 0.05) between groups based on the interaction effect shown by the ANOVA.
TABLE 1 - Changes in (mean ± SD, n = 13/group) maximal voluntary isokinetic concentric contraction torque at 60°·s−1 (MVC), ROM of the knee joint, muscle soreness (SOR) and plasma CK activity for the contralateral (Cont-KE-EF) and ipsilateral knee extensors (Ipsi-KE-EF) and flexors (Cont-KF-EF, Ipsi-KF-EF) groups before (pre), immediately after (post), and at 1–5 d (d1–d5) after the first bouts of MaxEC (MaxEC1) of the knee extensors (KE) and flexors (KF).
Variables Groups Pre Post d1 d2 d3 d4 d5
MVC, N·m Cont-KE-EF 117.0 ± 12.3 110.4 ± 11.3* 114.5 ± 11.0* 117.2 ± 11.4 117.5 ± 12.5 117.6 ± 13.1 117.3 ± 14.5
Ipsi-KE-EF 114.0 ± 12.0 106.2 ± 11.2* 108.8 ± 11.5* 112.4 ± 11.9 113.3 ± 11.3 114.3 ± 12.1 115.1 ± 12.1
Cont-KF-EF 52.8 ± 7.4 38.1 ± 9.3* 40.2 ± 7.9* 43.5 ± 7.1* 46.4 ± 7.3* 48.5 ± 7.8* 52.0 ± 7.9
Ipsi-KF-EF 50.1 ± 8.9 36.7 ± 7.5* 40.5 ± 9.0* 43.1 ± 8.8* 45.2 ± 8.7* 47.5 ± 9.3* 49.9 ± 8.4
ROM,° Cont-KE-EF 106.1 ± 4.6 103.7 ± 4.4* 102.9 ± 4.4* 103.8 ± 4.5* 104.7 ± 4.5* 105.5 ± 4.6* 106.2 ± 4.6
Ipsi-KE-EF 105.8 ± 3.5 102.9 ± 3.8* 102.2 ± 3.5* 103.2 ± 3.4* 104.2 ± 3.3* 105.1 ± 3.3 105.7 ± 3.5
Cont-KF-EF 108.5 ± 3.8 102.3 ± 5.4* 101.3 ± 4.2* 102.8 ± 4.0* 103.9 ± 3.8* 105.1 ± 3.8* 106.4 ± 3.8*
Ipsi-KF-EF 107.4 ± 5.1 101.7 ± 5.1* 100.9 ± 5.6* 101.7 ± 5.7* 102.5 ± 5.9* 103.5 ± 6.2* 104.5 ± 6.2*
SOR, mm Cont-KE-EF 0 ± 0 –– 13 ± 9* 18 ± 11* 8 ± 9* 6 ± 7* 3 ± 4*
Ipsi-KE-EF 0 ± 0 –– 15 ± 14* 15 ± 14* 10 ± 10* 8 ± 9* 1 ± 2
Cont-KF-EF 0 ± 0 –– 25 ± 16* 24 ± 13* 18 ± 11* 10 ± 7* 4 ± 4*
Ipsi-KF-EF 0 ± 0 –– 26 ± 22* 24 ± 18* 16 ± 13* 9 ± 9* 4 ± 4*
CK, IU·L−1 Cont-KE-EF 128 ± 10 –– 381 ± 235* 464 ± 396* 713 ± 770* 814 ± 1027* 574 ± 650*
Ipsi-KE-EF 121 ± 19 –– 361 ± 234* 432 ± 382* 728 ± 857* 796 ± 1115* 541 ± 694*
Cont-KF-EF 132 ± 12 –– 291 ± 192* 905 ± 544* 2365 ± 1881* 3424 ± 2876* 1619 ± 1312*
Ipsi-KF-EF 138 ± 18 –– 186 ± 56* 857 ± 434* 2187 ± 1763* 3188 ± 1664* 1655 ± 1623*
*Significant (P < 0.05) difference compared with preexercise (pre) level.

Eccentric Exercise

The average peak torque during EF MaxEC was similar (P = 0.955, η2 = 0.042) between the first (40 ± 6 N·m) and second MaxEC (40 ± 8 N·m) of the control group and the Cont-KE-EF (39 ± 6 N·m), Ipsi-KE-EF (38 ± 8 N·m), Cont-KF-EF (42 ± 5 N·m), and Ipsi-KF-EF (40 ± 6 N·m) groups. No significant difference was observed between right and left legs for the average peak torque during KE MaxEC between the Cont-KE-EF (203 ± 44 N·m) and Ipsi-KE-EF (202 ± 29 N·m) groups (P = 0.902, η2 = 0.001) and during KF MaxEC between the Cont-KF-EF (98 ± 8 N·m) and Ipsi-KF-EF (102 ± 5 N·m) groups (P = 0.752, η2 = 0.038).

The average total work during EF eccentric exercise was also similar (P = 0.219, η2 = 0.094) between the first (1270 ± 250 J) and second MaxEC (1224 ± 193 J) of the control group and the Cont-KE-EF (1118 ± 285 J), Ipsi-KE-EF (1164 ± 289 J), Cont-KF-EF (1155 ± 207 J), and Ipsi-KF-EF (1120 ± 111 J) groups. No significant difference was also observed between legs for the average peak torque during KE MaxEC for the Cont-KE-EF (4911 ± 522 N·m) and Ipsi-KE-EF (4703 ± 733 N·m) groups (P = 0.859, η2 = 0.026) and for the average peak torque during KF MaxEC for the Cont-KF-EF (2379 ± 364 N·m) and Ipsi-KF-EF (2316 ± 382 N·m) groups (P = 0.574, η2 = 0.058).

Changes in the Dependent Variables after KE and KF MaxEC

As shown in Table 1, significant (P < 0.05) changes in MVC torque after the KE or KF MaxEC were evident without significant differences between the Cont-KE-EF and Ipsi-KE-EF groups (interaction effect: P = 0.389, η2 = 0.082) and the Cont-KF-EF and Ipsi-KF-EF groups (interaction effect: P = 0.837, η2 = 0.037). This was also the case (P > 0.05) for ROM, muscle soreness, and plasma CK activity, and no significant (P > 0.05) differences were observed between the Cont-KE-EF and Ipsi-KE-EF groups and between the Cont-KF-EF and Ipsi-KF-EF groups (Table 1).

Changes in the Dependent Variables after EF MaxEC

MVC torque

Changes in EF MVC torque after EF MaxEC of the experimental groups (Cont-KE-EF, Ipsi-KE-EF, Cont-KF-EF, and Ipsi-KF-EF) were similar to those of the first bout of the control group (interaction effect: P = 0.529, η2 = 0.074; Fig. 1). The decreases in MVC torque immediately after the second bout of the control group was significantly smaller (P < 0.001, η2 = 0.378) than those of the first bout of the control group, and the four experimental groups showed similar changes (P = 0.384, η2 = 0.082) to those after the first bout of the control group. The recovery of MVC torque after the second bout of the control group was significantly faster than that of the first bout of the control group (interaction effect: P < 0.001, η2 = 0.538) and the Cont-KE-EF (P < 0.001, η2 = 0.412), Ipsi-KE-EF (P < 0.001, η2 = 0.398), Cont-KF-EF (P < 0.001, η2 = 0.524), and Ipsi-KF-EF groups (P < 0.001, η2 = 0.468; Fig. 1).

ROM

The changes in ROM after EF MaxEC of the four experimental groups were similar to those of the first bout of the control group (interaction effect: P = 0.953, η2 = 0.045; Fig. 2). The decreases in ROM immediately after the second bout of the control group were significantly smaller (P = 0.011, η2 = 0.215) than those of the first bout of the control group and the four experimental groups, without significant differences (P = 0.901, η2 = 0.021) among the first bout of the control group and the four experimental groups. The recovery of ROM after the second bout of the control group was significantly faster than that of the first bout of the control group (P = 0.023, η2 = 0.180) and the Cont-KE-EF (P < 0.001, η2 = 0.374), Ipsi-KE-EF (P < 0.001, η2 = 0.306), Cont-KF-EF (P < 0.001, η2 = 0.325), and Ipsi-KF-EF groups (P < 0.001, η2 = 0.291; Fig. 2).

Muscle soreness

The extent of muscle soreness developed after EF MaxEC of the Cont-KE-EF, Ipsi-KE-EF, Cont-KF-EF, and Ipsi-KF-EF groups was similar to that of the first bout of the control group (interaction effect: P = 0.992, η2 = 0.035; Fig. 3). The magnitude of muscle soreness after the second bout of the control group was significantly smaller than those of the first bout of the control group (P < 0.001, η2 = 0.559) and the Cont-KE-EF (P = 0.001, η2 = 0.279), Ipsi-KE-EF (P < 0.001, η2 = 0.305), Cont-KF-EF (P < 0.001, η2 = 0.455), and Ipsi-KF-EF groups (P < 0.001, η2 = 0.339; Fig. 3).

Plasma CK activity

Changes in plasma CK activity after EF MaxEC of the Cont-KE-EF, Ipsi-KE-EF, Cont-KF-EF, and Ipsi-KF-EF groups were similar to those of the first bout of the control group (interaction effect: P = 0.887, η2 = 0.050; Fig. 4). The increase in plasma CK activity after the second bout of the control group was significantly smaller than that after the first bout of the control group (P < 0.001, η2 = 0.573), and also that after the second bout of the Cont-KE-EF (P < 0.001, η2 = 0.479), Ipsi-KE-EF (P < 0.001, η2 = 0.427), Cont-KF-EF (P < 0.001, η2 = 0.818), and Ipsi-KF-EF groups (P < 0.001, η2 = 0.761; Fig. 4).

DISCUSSION

The present study found that muscle damage after EF eccentric exercise that was performed 1 wk after the KE or KF eccentric exercise was not significantly different from that after the first bout of EF eccentric exercise without the leg exercise. In addition, the changes in muscle damage markers after EF eccentric exercise were not affected by the greater changes in the markers after KF than KE eccentric exercise (Figs. 1–4), and no significant differences were evident between the ipsilateral and contralateral sides (Table 1). These results do not support the hypotheses that the protective effects against muscle damage after EF eccentric exercise would be conferred by the leg eccentric exercises, and the protective effect would be greater by KF than KE eccentric exercise. These suggest that no muscle damage–protective effect was transferred from leg to arm muscles.

As shown in Table 1, significant changes in muscle damage markers after the KE or KF MaxEC were observed, without significant differences between the ipsilateral and contralateral sides to the nondominant arm that performed the subsequent eccentric exercise of the EF. The peak torque and work generated during the KE or KF MaxEC between ipsilateral and contralateral limbs were similar. The magnitude of the changes in muscle damage markers after KE or KF MaxEC in the present study (Table 1) was similar to that reported in the previous studies (9,14,20). The present study confirmed that the extent of muscle damage was significantly greater after KF than KE eccentric exercise (14,27). No significant differences in the changes in the muscle damage markers after eccentric exercise between dominant and nondominant legs were also in line with the findings of the previous studies (2,9).

The changes in the muscle damage markers after the first MaxEC of the control group (Figs. 1–4) were similar to those reported in the previous studies in which a similar eccentric exercise of the EF was performed by sedentary men (8,17). This suggests that the responses to the first EF MaxEC of the control group (e.g., MVC torque at 1 d post, −42%; ROM at 1 d post, −13°; peak soreness; 50 mm; peak CK activity; 5914 IU·L−1) were typical. Also, the changes in muscle damage markers (Figs. 1–4) after the second EF MaxEC performed by the opposite arm in the control group (e.g., MVC torque at 1 d post, −23%; ROM at 1 d post, −8°; peak soreness, 21 mm; peak CK activity, 2109 IU·L−1) were similar to those reported in the previous study (8) in which the contralateral repeated bout effect was found (−28%, −9°, 25 mm, 2075 IU·L−1). Thus, the smaller changes in the variables following the second EF MaxEC of the control group were most likely due to the contralateral repeated bout effect (8,9,12,18).

The most important findings of the current study were that changes in all muscle damage markers after the EF MaxEC of the experimental (Cont-KE-EF, Ipsi-KE-EF, Cont-KF-EF, and Ipsi-KF-EF) groups were similar to those after the first EF MaxEC of the control group (Figs. 1–4). If the leg exercises had conferred some protective effect against EF MaxEC, the changes in the muscle damage markers would have been smaller than those after the first EF MaxEC of the control group. Therefore, these results do not support the hypothesis that EF MaxEC-induced muscle damage would be attenuated by prior KE or KF MaxEC. Three review articles about the repeated bout effect (3,13,28) stated that one of the mechanisms underpinning the contralateral repeated bout effect would be adaptations of systemic inflammation. If the adaptations include an increased immunity, it may be that muscle damage induced by the first eccentric exercise bout increases the immunity to reduce the magnitude of muscle damage in the subsequent bout of eccentric exercise, regardless of the muscles involved in the first exercise.

Xin et al. (7) demonstrated that the magnitude of increase in inflammatory-related transcription factor nuclear factor κ–light-chain-enhancer of activated B cells (NF-κB) in the vastus lateralis after 100 MaxEC of the knee extensors (122.9% ± 2.6%) was reduced after the second bout of the same eccentric exercise performed by the opposite leg (109.1% ± 3.0%). The authors stated that the contralateral repeated bout effect could be due to the reduced increase in NF-κB activity after exercise in the nonexercising opposite knee extensors. Deyhle et al. (29) have recently reported interesting results in animal studies in which the role of adaptive immunity in the repeated bout effect was examined by testing the “T-cell memory hypothesis.” They found that electrically stimulated lengthening contractions of tibialis anterior muscle of one limb elicited the repeated bout but not the contralateral repeated bout effect, and increases in several subsets of T cells including conventional CD4+, CD8+, memory, and regulatory T cells found after the first bout were minimal after the second bout. Interestingly, adoptive T-cell transfer from damage-experienced rats did not confer protection to damage-naive recipient rats. It was concluded that T cells were unlikely to mediate the protective adaptations of the repeated bout effect in a manner similar to their role in adaptive immunity, but other immune cells might play an active role in the development of the repeated bout effect. Because nonhomologous muscles did not confer protection, the present study casts doubt on a systemic inflammation-related adaptation as a mechanism of the repeated bout effect.

Hyldahl et al. (3) stated that the muscle damage–protective effect would be conferred by a combination of neural adaptations (e.g., shift in motor unit recruitment, increased α-motoneuron excitability, and increased inhibitory feedback), muscle–tendon complex behavior changes (e.g., reduced in fascicle elongation, increased tendon compliance, and smaller displacement of myotendinous junction), and extracellular matrix structural remodeling (e.g., initial ECM de-adhesion, delayed ECM adhesion, and collagen expression). Because it is unlikely that peripheral adaptations at the level of muscle fibers and extracellular matrix are transferred from one muscle to the other even for the homologous muscle of the contralateral limb, it seems that the contralateral protective effect is more associated with neural adaptations (3–5,12). If a previous bout of eccentric exercise increases recruitment of low-threshold motor units to sustain similar workloads in a subsequent bout performed on the contralateral limb (4,12), it seems reasonable to assume that this adaptation may be more specific to the muscles used in the exercise and thus will not be transferred from a leg to an arm muscle. The exact mechanisms underpinning the “cross-transfer” or “cross-education” effect are not known, although the phenomena of the “cross” effect have been known for a long time (30–32). It has been documented that unilateral resistance training activates neural circuits that chronically modify the efficacy of motor pathways that project to the opposite untrained limb and/or induce adaptations in motor areas that are primarily involved the control of movements of the trained limb, and the opposite untrained limb may access these modified neural circuits (30–34). It is not known how such adaptations, if any, are produced, and whether they are limited to only homologous muscles. Further studies are necessary to elucidate the mechanisms underpinning the contralateral repeated bout effect by investigating how the protective effect is conferred to the homologous muscle of the contralateral limb.

The current study had some limitations, which should be considered for designing future studies. First, sedentary young men were used as participants in the current study. Thus, the findings of the present study cannot be generalized to other populations. Second, the interval between the first and second eccentric exercise bouts was set at 1 wk in the present study. Previous studies reported that the greatest extent of the contralateral repeated bout effect was evident at 1-d interval for the EF (8) and the KF (9). It is important to confirm that the contralateral protective effect is not transferred from leg to arm muscles, even if the interval between the exercises was shorter such as 1 d. Third, muscle damage was determined by indirect markers only, and no neuromuscular measures using EMG and TMS or invasive techniques (muscle biopsies) to assess histological, biochemical, and molecular biological measures were included in the present study. Lastly, the present study did not include conditions to examine the protective effect of an initial bout on antagonist muscle of the same limb (e.g., elbow extensors–EF or knee extensors–KF) or the contralateral limb (e.g., one arm: elbow extensors–opposite arm: EF, one leg: knee extensors–opposite leg: KF). To ensure that the protective effect against muscle damage is conferred to the homologous muscle only, the effect on antagonist muscles in the same limb and opposite limb should be investigated.

In conclusion, the results of the current study showed that no protective effect on EF eccentric exercise was conferred by leg eccentric exercises and thus clarified that no muscle damage–protective effect was transferred from the knee extensors or KF to the EF. It seems that the repeated bout effect only occurs in the same muscles and the contralateral homologous muscles. Future studies are warranted to investigate why only homologous muscles are affected.

The authors would like to thank Mr. Shang-Hen Wu for his assistance for the data collection and Dr Ming-Ju Lin for allowing the of use his laboratory and equipment for collecting some data. This work was supported by the Ministry of Science and Technology (MOST 108-2410-H-003-116-MY3) and the Higher Education Sprout Project by the Ministry of Education, Taiwan.

The authors declare that they have no conflict of interest. The results of the present study do not constitute endorsement by American College of Sports Medicine. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

REFERENCES

1. Nosaka K, Sakamoto K, Newton M, Sacco P. How long does the protective effect on eccentric exercise-induced muscle damage last? Med Sci Sports Exerc. 2001;33(9):1490–5.
2. Hody S, Rogister B, Leprince P, Laglaine T, Croisier JL. The susceptibility of the knee extensors to eccentric exercise-induced muscle damage is not affected by leg dominance but by exercise order. Clin Physiol Funct Imaging. 2013;33(5):373–80.
3. Hyldahl RD, Chen TC, Nosaka K. Mechanisms and mediators of the skeletal muscle repeated bout effect. Exerc Sport Sci Rev. 2017;45(1):24–33.
4. Tsuchiya Y, Nakazato K, Ochi E. Contralateral repeated bout effect after eccentric exercise on muscular activation. Eur J Appl Physiol. 2018;118(9):1997–2005.
5. McHugh MP. Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise. Scand J Med Sci Sports. 2003;13(2):88–97.
6. Pincheira PA, Hoffman BW, Cresswell AG, Carroll TJ, Brown NAT, Lichtwark GA. The repeated bout effect can occur without mechanical and neuromuscular changes after a bout of eccentric exercise. Scand J Med Sci Sports. 2018;28(10):2123–34.
7. Xin L, Hyldahl RD, Chipkin SR, Clarkson PM. A contralateral repeated bout effect attenuates induction of NF-κB DNA binding following eccentric exercise. J Appl Physiol (1985). 2014;116(11):1473–80.
8. Chen TC, Chen HL, Lin MJ, Yu HI, Nosaka K. Contralateral repeated bout effect of eccentric exercise of the elbow flexors. Med Sci Sports Exerc. 2016;48(10):2030–9.
9. Chen TC, Lin MJ, Chen HL, Yu HI, Nosaka K. Contralateral repeated bout effect of the knee flexors. Med Sci Sports Exerc. 2018;50(3):542–50.
10. Marathamuthu S, Selvanayagam VS, Yusof A. Contralateral effects of eccentric exercise and DOMS of the plantar flexors: evidence of central involvement. Res Q Exerc Sport. 2020. doi:10.1080/02701367.2020.1819526.
11. Howatson G, van Someren KA. Evidence of a contralateral repeated bout effect after maximal eccentric contractions. Eur J Appl Physiol. 2007;101(2):207–14.
12. Starbuck C, Eston RG. Exercise-induced muscle damage and the repeated bout effect: evidence for cross transfer. Eur J Appl Physiol. 2012;112(3):1005–13.
13. Deyhle MR, Hyldahl RD. The role of T lymphocytes in skeletal muscle repair from traumatic and contraction-induced injury. Front Physiol. 2018;9:768.
14. Chen TC, Lin KY, Chen HL, Lin MJ, Nosaka K. Comparison in eccentric exercise-induced muscle damage among four limb muscles. Eur J Appl Physiol. 2011;111(2):211–23.
15. Newton MJ, Sacco P, Chapman D, Nosaka K. Do dominant and non-dominant arms respond similarly to maximal eccentric exercise of the elbow flexors? J Sci Med Sport. 2013;16(2):166–71.
16. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale (NJ): Lawrence Erlbaum Associates; 1988. pp. 55–7.
17. Tseng WC, Nosaka K, Tseng KW, Chou TY, Chen TC. Contralateral effects by unilateral eccentric versus concentric resistance training. Med Sci Sports Exerc. 2020;52(2):474–83.
18. Chou YC, Chen HL, Chen TC, Lin MJ. Eccentric exercise-induced different magnitude of variability in blood creatine kinase and indirect markers of muscle damage. Phys Educ J. 2018;51(1):13–24.
19. Huang GL, Chen HL, Nosaka K, Chen TC. Effect of performing order of the first and repeated bouts of maximal eccentric exercise of the right and left elbow flexors on arterial stiffness. Phys Educ J. 2016;49(2):143–56.
20. Lin MJ, Chen TC, Chen HL, Wu BH, Nosaka K. Low-intensity eccentric contractions of the knee extensors and flexors protect against muscle damage. Appl Physiol Nutr Metab. 2015;40(10):1004–11.
21. Chen HY, Chen YC, Tung K, Chao HH, Wang HS. Effects of caffeine and sex on muscle performance and delayed-onset muscle soreness after exercise-induced muscle damage: a double-blind randomized trial. J Appl Physiol (1985). 2019;127(3):798–805.
22. Liu HW, Cheng HC, Tsai SH, Sun WH. Effect of progressive resistance training on circulating adipogenesis-, myogenesis-, and inflammation-related microRNAs in healthy older adults: an exploratory study. Gerontology. 2020;66(6):562–70.
23. Chen WH, Wu HJ, Lo SL, et al. Eight-week battle rope training improves multiple physical fitness dimensions and shooting accuracy in collegiate basketball players. J Strength Cond Res. 2018;32(10):2715–24.
24. Chen YT, Hsieh YY, Ho JY, Lin JC. Effects of running exercise combined with blood flow restriction on strength and sprint performance. J Strength Cond Res. 2019. doi:10.1519/JSC.0000000000003313.
25. Chen WH, Yang WW, Lee YH, Wu HJ, Huang CF, Liu C. Acute effects of battle rope exercise on performance, blood lactate levels, perceived exertion, and muscle soreness in collegiate basketball players. J Strength Cond Res. 2020;34(10):2857–66.
26. Bakeman R. Recommended effect size statistics for repeated measures designs. Behav Res Methods. 2005;37:379–84.
27. Franklin ME, Chamness MS, Chenier TC, Mosteller GC, Barrow LA. A comparison of isokinetic eccentric exercise on delayed-onset muscle soreness and creatine kinase in the quadriceps versus the hamstrings. Isokinet Exerc Sci. 1993;3(2):68–73.
28. Fatouros IG, Jamurtas AZ. Insights into the molecular etiology of exercise-induced inflammation: opportunities for optimizing performance. J Inflamm Res. 2016;9:175–86.
29. Deyhle MR, Carlisle M, Sorensen JR, et al. Accumulation of skeletal muscle T cells and the repeated bout effect in rats. Med Sci Sports Exerc. 2020;52(6):1280–93.
30. Carroll TJ, Herbert RD, Munn J, Lee M, Gandevia SC. Contralateral effects of unilateral strength training: evidence and possible mechanisms. J Appl Physiol (1985). 2006;101(5):1514–22.
31. Lee M, Carroll TJ. Cross education: possible mechanisms for the contralateral effects of unilateral resistance training. Sports Med. 2007;37(1):1–14.
32. Farthing JP. Cross-education of strength depends on limb dominance: implications for theory and application. Exerc Sport Sci Rev. 2009;37(4):179–87.
33. Kidgell DJ, Frazer AK, Daly RM, et al. Increased cross-education of muscle strength and reduced corticospinal inhibition following eccentric strength training. Neuroscience. 2015;300:566–75.
34. Frazer AK, Pearce AJ, Howatson G, Thomas K, Goodall S, Kidgell DJ. Determining the potential sites of neural adaptation to cross-education: implications for the cross-education of muscle strength. Eur J Appl Physiol. 2018;118(9):1751–72.
Keywords:

REPEATED BOUT EFFECT; CROSS-TRANSFER EFFECT; KNEE EXTENSORS; KNEE FLEXORS; MUSCLE FUNCTION; MUSCLE SORENESS; CREATINE KINASE

Copyright © 2021 by the American College of Sports Medicine