Recovery From 50 Eccentric Biceps Curls in Young, Untrained Men and Women

Muscle Damage Clinical Trial

Official title:

Recovery After Exercise-Induced Muscle Damage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05036239
• Other study ID #: EIMD19
• Status: Completed
• Phase: N/A
• Start date: December 3, 2019
• Est. completion date: December 20, 2020

Study information

• Verified date: November 2023
• Source: Norwegian School of Sport Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to investigate muscle stiffness in relation to muscle damaging work and to investigate how well the change in muscle stiffness correlates with the degree of muscle damage (myofibrillar disruption and necrosis). To date, the reduction in force-generating capacity is the best non-invasive marker of muscle damage. It is already established that muscle stiffness correlates well with the decline in force-generating capacity after damaging exercise. However, the correlation between degree of muscle damage and muscle stiffness has not yet been investigated. The main focus of the study is therefore to investigate the relationship between muscle stiffness and muscle damage. Further, the researchers aim to investigate how calcium cycling is affected by damaging work, and if impaired calcium cycling may partially explain the observed reduction in force-generating capacity.

Description:

Regardless of whether an individual is in rehabilitation or exercise for general health or athletic performance, resistance exercise is an essential form of exercise when the goal is to increase muscle mass, strength and function. Although, resistance exercise primarily is associated with positive effects it may also result in muscle damage when the exercise is of high intensity and/or unaccustomed. This is known as exercise-induced muscle damage (EIMD) and is reflected by a substantial decrease in force-generating capacity and often accompanied by intracellular swelling and delayed onset muscle soreness. On a cellular level, EIMD include myofibrillar disruption, inflammatory response and in severe cases of EIMD; myofibre necrosis. While EIMD with its symptoms clearly is evident, its underlying mechanisms are still to be fully elaborated.

One interesting hypothesis regarding the molecular basis of decreased muscle strength as a result of EIMD, is related to the strain of this exercise mode causing "popped" sarcomeres. When sarcomeres are stretched beyond actin-myosin overlap, some sarcomeres may over-stretch. This results in overload of membranes, leading to opening of stretch-activated channels, and subsequently influx of Ca2+. High levels of cytoplasmic Ca2+ may cause degradation of contractile proteins or Excitation-Contraction coupling proteins mediated through increased calpain activity. However, a recent study by Cully and colleagues (2017) suggest a protective mechanism post heavy-load strength training related to Ca2+-handling. Cully et al. observed formation of vacuoles in longitudinally connecting tubules post exercise when exposing fibers to 1.3 μM [Ca2+] in the cytoplasma. These vacuoles provide an enclosed compartment where Ca2+ can be accumulated, preventing Ca2+ from initiating damage to the muscle. The role of Ca2+-regulation in recovery of muscle function warrants further investigation and clarification.

To the best of the investigators knowledge, the most valid method for estimating EIMD is by investigating myofibrillar disruption, and in some cases necrosis, in muscle biopsies. This requires many resources and is rather expensive. Currently, the best non-invasive marker of muscle damage is the force deficit observed at 48 hours post exercise. However, a measurement estimating muscle damage immediately post exercise is warranted because force deficit immediately post exercise will be confounded by muscle fatigue.

A novel study performed by Lacourpaille et al. (2017) showed a strong negative correlation (-0.80) between stiffness of the muscle tissue, shear modulus, measured 30 minutes post exercise and peak isometric force measured at 48 hours post exercise and therefore a strong relationship between the decline in force production capacity and increased stiffness post exercise, suggesting a possible method to predict EIMD immediately after exercise. However, direct evidence of this association is warranted, with measurements of shear modulus and EIMD biomarkers, such as the proportion of disrupted fibers and sarcoplasmic Ca2+ regulation.

The ability to predict EIMD after training is of great interest to athletes, but also patients suffering from e.g. muscular dystrophies. Being able to predict EIMD quickly and non-invasively after exercise will help employ optimal recovery.

The aim of this project is to investigate the link between exercise-induced muscle damage (EIMD) as changes in shear modulus by ultrasound shear wave elastography, and muscle damage as observed in the analysis of muscle biopsies. The hypothesis is that there is a strong relationship between muscle stiffness acute post exercise and degree of muscle damage observed in muscle biopsies. A secondary aim is to further the understanding of cellular mechanisms causing EIMD and the role of Ca2+ in the recovery of muscle function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 20, 2020
• Est. primary completion date: October 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• 18 to 35 years of age

Exclusion Criteria:

• Injury to the muscle-skeletal system

• Other conditions causing inability to perform heavy-load resistance exercise

• Having engaged in resistance exercise targeting the m. biceps brachii once a week or more over the past year

Related Conditions & MeSH terms

• Muscle Damage
• Muscle Stiffness
• Recovery

Intervention

Other:
• Eccentric biceps curls
10 x 5 repetitions of eccentric biceps curls, interspaced by 30 seconds of rest.

Locations

Country	Name	City	State
Norway	Norwegian School of Sport Sciences	Oslo

Sponsors (6)

Lead Sponsor	Collaborator
Norwegian School of Sport Sciences	Oslo University Hospital, Syddansk Universitet, Denmark, Université de Nantes, University of Copenhagen, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in HSP70	Localization of HSP70 in skeletal muscle using Western blotting	2 hours, 48 hours and 96 hours after eccentric biceps curls
Other	Change in AlphaB-crystallin	Localization of alphaB-crystallin in skeletal muscle using Western blotting	2 hours, 48 hours and 96 hours after eccentric biceps curls
Other	Change in Fiber-specific AlphaB-crystallin staining intensity	Change in staining intensity of AlphaB-crystallin in type-I and type-II skeletal muscle fibers using Immunohistochemistry	2 hours, 48 hours and 96 hours after eccentric biceps curls
Other	Change in Fiber-specific HSP70 staining intensity	Change in staining intensity of HSP70 in type-I and type-II skeletal muscle using Immunohistochemistry	2 hours, 48 hours and 96 hours after eccentric biceps curls
Other	Change in Fatigue	Electrical stimulation of m. biceps brachii at 20 and 50 Hz	Baseline and 1 hour after eccentric biceps curls
Other	Change in Muscle soreness	Subjective rating of muscle soreness using a VAS-scale (0-10)	Baseline, 15 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls
Other	Change in Muscle swelling (circumference)	Circumference of upper arm measured 2 cm above humeral epicondyles and midbelly of m. biceps brachii	Baseline, 15 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls
Other	Change in Muscle swelling (thickness)	Thickness at midbelly of m. biceps brachii using ultrasound B-mode	Baseline, 2 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls
Other	Change in Creatine kinase	Level of serum creatine kinase	Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
Other	Change in Myoglobin	Level of serum myoglobin	Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
Other	Change in Titin	Level of titin-N fragment in urine	Baseline, 2,5 hours, morning day 2, morning day 3, morning day 4, and morning day 5 after eccentric biceps curls
Other	Change in Troponin I	Level of serum Troponin I in fast and slow twitch muscle fibers	Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
Other	Change in Macrophage infiltration	Presence of macrophages in skeletal muscle using Immunohistochemistry	2 hours, 48 hours and 96 hours after eccentric biceps curls
Other	Muscle fiber type	Fiber type composition in cross-sections of muscle samples using Immunohistochemistry	2 hours after eccentric biceps curls
Other	Muscle fiber type	Fiber type composition in cross-sections of muscle samples using Immunohistochemistry	48 hours after eccentric biceps curls
Other	Muscle fiber type	Fiber type composition in cross-sections of muscle samples using Immunohistochemistry	96 hours after eccentric biceps curls
Other	Change in Calcium-related protein abundances in skeletal muscle	Levels of proteins and phosphorylation status using Western blotting	2 hours, 48 hours and 96 hours after eccentric biceps curls
Primary	Change in muscle strength	Recovery of arm flexion torque	Baseline, and 5 minutes, 3 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
Primary	Change in muscle stiffness	Muscle stiffness measured with shear wave elastography as mean young modulus in different conditions (static and dynamic)	Baseline, and 50 minutes, 3 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
Primary	Change in muscle damage	Development of myofibrillar disruption and necrosis observed in skeletal muscle biopsies with electron and confocal microscopy	2 hours, 48 hours, and 96 hours after eccentric biceps curls
Primary	Change in calcium cycling	Calcium cycling in muscle single fibers and Sarcoplasmic reticulum-homogenate	2 hours, 48 hours and 96 hours after eccentric biceps curls
Secondary	Change in organization of the tubular system in skeletal muscle	Quantification of transverse and longitudinal tubules, and number of Vacuoles in single fibers using confocal microscopy	2 hours, 48 hours and 96 hours after eccentric biceps curls