TY - JOUR

T1 - Ischemic preconditioning improves microvascular endothelial function in remote vasculature by enhanced prostacyclin production

AU - Rytter, Nicolai

AU - Carter, Howard

AU - Piil, Peter

AU - Sørensen, Henrik

AU - Ehlers, Thomas

AU - Holmegaard, Frederik

AU - Tuxen, Christoffer

AU - Jones, Helen

AU - Thijssen, Dick

AU - Gliemann, Lasse

AU - Hellsten, Ylva

N1 - CURIS 2020 NEXS 248

PY - 2020

Y1 - 2020

N2 - Background: The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. Methods and Results: A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (P<0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (P<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (P<0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. Conclusions: These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation.

AB - Background: The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. Methods and Results: A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (P<0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (P<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (P<0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. Conclusions: These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation.

KW - Faculty of Science

KW - Ischemic preconditioning

KW - Microvascular endothelial function

KW - Platelets

KW - Prostacyclin

KW - Vasodilation

U2 - 10.1161/JAHA.120.016017

DO - 10.1161/JAHA.120.016017

M3 - Journal article

C2 - 32750305

VL - 9

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 15

M1 - e016017

ER -