Compliance-mediated pressure-independent cerebrovascular regulation: a distinct novel mechanism in youth

Cerebrovascular regulatory capacity is essential for maintaining brain stability. Most previous studies have focused on middle-aged and elderly populations, where regulation depends on vasodilation with reduced resistance and elevated blood pressure-the pressure-dependent mechanism. Whether this paradigm applies to younger individuals remains unclear. Given the rising prevalence of cardiovascular and cerebrovascular risks in young adults, elucidating youth-specific mechanisms is of great importance. In this study, standardized breath-holding was used to induce hypercapnia in 52 young volunteers (23.67 ± 1.77 years). Hemodynamic parameters of both middle cerebral arteries (blood pressure, heart rate, and flow velocity) were measured at rest and during hypercapnia. The breath-holding index (BHI), reflecting cerebrovascular regulatory capacity, was calculated, and a hemodynamic model was applied to derive resistance variation coefficient (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>R</mml:mi><mml:mi>v</mml:mi></mml:msub></mml:math>), diameter variation coefficient (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>D</mml:mi><mml:mi>v</mml:mi></mml:msub></mml:math>), and compliance (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>C</mml:mi></mml:math>), forming a multiparametric framework. In total, 104 unilateral datasets underwent multilevel statistical analysis. Two regulatory patterns were identified: pressure-dependent (n = 72) and pressure-independent (n = 32). The pressure-independent group showed greater dilation (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>D</mml:mi><mml:mi>v</mml:mi></mml:msub></mml:math>: 1.4222 vs. 1.2817, p < 0.05) and more stable blood pressure (1.4271 vs. 5.3937 mmHg, p < 0.05), achieving comparable cerebrovascular regulatory capacity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mtext>BHI</mml:mtext></mml:math>: 1.3327 vs. 1.3907, p > 0.05) via enhanced compliance. Strong correlations were observed between rest and task states for blood pressure, heart rate, and flow velocity (all r > 0.85, p < 0.001). The proposed pressure-independent mechanism challenges the conventional paradigm, highlights individual variability, and offers new insights into cerebrovascular regulatory capacity under hypercapnia.