BACKGROUND The heart operates in concert with skeletal muscles to facilitate movement, maintain cardiovascular homeostasis, and adapt to exercise/fatigue. However, the exact mechanisms by which autonomic regulation of heart rate variability facilitates coordination with distinct muscle fibers within muscles remain unknown. Here we investigate how cardio-muscular coordination evolves in time and respond to fatigue during a maximal squat test. METHODS: Thirty healthy young adults performed two maximal body weight squat tests until exhaustion. During the protocol, simultaneous recordings were taken of a 3-lead electrocardiogram (EKG Lead II) along with electromyography (EMG) signals from the following muscles: left and right vastus lateralis (LegL, LegR); left and right erector spinae (BackL, BackR). We first obtained instantaneous heart rate (IHR, representing heart rate variability) derived from the EKG signal (Pan-Tomkins QRS detection), and decompose the EMG recordings in ten frequency bands [F1-F10], representing distinct muscle fiber types. We next quantified pairwise coupling (cross-correlation; amplitude-amplitude coupling) between the time series for IHR and all EMG spectral power frequency bands in each Leg and Back muscle. RESULTS: During Set 1, low [F1-F5] EMG frequency bands, associated with type-I slow muscle fibers, exhibited stronger coupling with IHR (CMEAN = 0.35: SD = 0.03) compared to intermediate/fast frequency [F6-F10] EMG bands (CMEAN = 0.20: SD = 0.02). With progression of fatigue in Set 2, a significant overall decline in coupling strength between IHR and all EMG frequency bands was observed. Notably, this decline was more pronounced between IHR and intermediate/high- [F6-F10] frequency EMG bands (98%; p = 0.003), representing type-IIa,b muscle fibers, compared to slow [F1-F5] bands (48%; p = 0.02). CONCLUSION: The overall stronger coupling between IHR and slow muscle fibers underscores the potentially vital role of heart rate variability in supporting the endurance-oriented function of these fibers, which rely on a steady supply of oxygen. The significant decline in coupling strength between IHR and all EMG frequency bands as fatigue progressed in Set 2 reflects the complex impact of exhaustion on cardiac and muscle function. This dynamic network approach can lead to the development of novel network-based markers to study multilevel cardio-muscular interactions.

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