The effect of hypoxemia on muscle sympathetic nerve activity and cardiovascular function: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis to determine the effect of acute poikilocapnic, high-altitude, and acute isocapnia hypoxemia on muscle sympathetic nerve activity (MSNA) and cardiovascular function. A comprehensive search across electronic databases was performed until June 2021. All observational designs were included: population (healthy individuals); exposures (MSNA during hypoxemia); comparators (hypoxemia severity and duration); outcomes (MSNA; heart rate, HR; and mean arterial pressure, MAP). Sixty-one studies were included in the meta-analysis. MSNA burst frequency increased by a greater extent during high-altitude hypoxemia [P < 0.001; mean difference (MD), +22.5 bursts/min; confidence interval (CI) = -19.20 to 25.84] compared with acute poikilocapnic hypoxemia (P < 0.001; MD, +5.63 bursts/min; CI = -4.09 to 7.17) and isocapnic hypoxemia (P < 0.001; MD, +4.72 bursts/min; CI = -3.37 to 6.07). MSNA burst amplitude was only elevated during acute isocapnic hypoxemia (P = 0.03; standard MD, +0.46 au; CI = -0.03 to 0.90), and MSNA burst incidence was only elevated during high-altitude hypoxemia [P < 0.001; MD, 33.05 bursts/100 heartbeats; CI = -28.59 to 37.51]. Meta-regression analysis indicated a strong relationship between MSNA burst frequency and hypoxemia severity for acute isocapnic studies (P < 0.001) but not acute poikilocapnia (P = 0.098). HR increased by the same extent across each type of hypoxemia [P < 0.001; MD +13.81 heartbeats/min; 95% CI = 12.59-15.03]. MAP increased during high-altitude hypoxemia (P < 0.001; MD, +5.06 mmHg; CI = 3.14-6.99), and acute isocapnic hypoxemia (P < 0.001; MD, +1.91 mmHg; CI = 0.84-2.97), but not during acute poikilocapnic hypoxemia (P = 0.95). Both hypoxemia type and severity influenced sympathetic nerve and cardiovascular function. These data are important for the better understanding of healthy human adaptation to hypoxemia.