The Relationship Between Skeletal Muscle Mitochondrial Function and Cardiac Workload During Exercise in Young Healthy Subjects

Exaggerated cardiac workload responses to incremental exercise are associated with the development of hypertension and future cardiovascular events. We hypothesized that skeletal muscle mitochondrial function is associated with cardiac workload, quantified as Rate Pressure Product (RPP), during exercise. Healthy adults (n = 18; 9 females; age 25 ± 4 years) performed a maximal exercise test on a cycle ergometer. The test began at 0 W and followed an incremental protocol starting at 40 W, with load increases every 2 minutes until exhaustion. Breath-by-breath gas exchange was measured to determine peak oxygen uptake and the respiratory compensatory point (RCP). Heart rate (HR) and systolic blood pressure (BP) were recorded at each load to calculate RPP. The cardiac workload response to exercise was defined as the change in RPP from 0 W to the intensity corresponding to RCP (ΔRPP). Muscle biopsies from the vastus lateralis were collected on separate days to assess mitochondrial respiration. ΔRPP from 0 W to RCP intensity was 18181 ± 2147 mmHg·bpm and Complex I mediated respiration was 31.9 ± 13.7 pmol·mg^-1 s^-1. ΔRPP was correlated only with Complex I (r = -0.69, p = 0.002) and sex (r = 0.50, p = 0.035). In a forward stepwise linear regression analysis with ΔRPP as the dependent variable and baseline RPP, sex, and complex I mediated respiration as predictors, complex I mediated respiration was the only variable significantly associated with ΔRPP (adjusted R² = 0.44; unstandardized β = -107; 95% CI:-167 to -47; p = 0.002). The cardiac workload response to exercise is strongly associated with skeletal muscle mitochondrial function in young normotensive individuals.