Introduction: The upper limit of brachial artery (BA) flow-mediated dilation (FMD) has not been thoroughly interrogated, and long duration occlusion + handgrip exercise may create larger shear stress stimuli than previous manipulations.

Purpose: To determine whether novel combinations of occlusion + handgrip exercise can extend the range of FMD stimulus-response relationship characterization and permit identification of a BA-FMD response ceiling.

Methods: Ten healthy subjects performed eight reactive hyperemia (RH) FMD trials: 5, 10, and 15 min of occlusion (5RH, 10RH, 15RH); 5, 10 and 15 min of occlusion + 3-min ischemic exercise (IE) (5IE, 10IE, 15IE); 10 and 15 min of occlusion + 3-min IE + 4-min post-occlusion exercise (PE) (10IEPE, 15IEPE). Shear stress was estimated as shear rate (SR = blood velocity/BA diameter; (ultrasound assessment)) (SR stimulus = area under the curve (AUC) until peak diameter). Data are mean ± SE.

Results: There were no differences in SR-AUC among IE and IEPE trials (p > 0.70), however, IE consistently increased the SR-AUC (IE + IEPE trial average 17,845.1 ± 2,023.3 a.u.) vs. the 5RH and 10RH trials (4,943.0 ± 428.4 a.u., 6,800.6 ± 805.9 a.u.) (p < 0.05). The %FMD ranged from 7.3 ± 0.8% (5RH) to 19.1 ± 2.0% (15IEPE) (p < 0.001) with no differences among IE and IEPE trials (p > 0.16). FMD increased with increasing SR-AUC (all subjects, all trials: r(2) 0.36, p < 0.001) CONCLUSIONS: The stimulus created by brief (5 min) occlusion + ischemic exercise was not significantly enhanced by prolonging occlusion or continuing to exercise post-occlusion. The FMD response did not clearly plateau with increasing stimulus magnitude; however, the FMD capacity was shown to be more than double the FMD magnitude that was elicited with a standard 5-min occlusion test.