Preconditioning and Shear Stress in the Microcirculation in Ischemia-Reperfusion Injury

Abstract

Postischemic reperfusion causes microvascular endothelial cell dysfunction characterized by low shear stress, excessive oxidative stress and a reduced nitric oxide (NO) release. Recent studies have demonstrated that reduced shear forces are responsible for the impairment of endothelium-dependent vasodilation after ischemia reperfusion (I/R) injury. Preconditioning is an endogenous phenomenon whereby intermittent periods of ischemia provide protection against subsequent periods of I/R. Several models show that intermittent hypoxia (IH, brief periods of systemic hypoxia and reoxygenation), treatment with erythropoietin (EPO) and ultrasound exposure are methods of preconditioning. This chapter explores the hypothesis that these procedures that improve tolerance to subsequent I/R are directly related to shear stress. It acts as a biochemical mechanotransducer by modulating the production of vasoactive substances by endothelial cells. The adaptation of endothelial cells to high shear stress during the preconditioning period is crucial to ensure vasodilation and capillary perfusion during subsequent periods of I/R. Both IH and EPO treatment increase blood viscosity thus increasing shear stress associated with a reduced oxidative stress during postischemic reperfusion. Ultrasound treatment can also improve tolerance to I/R and normale shear stress during postischemic reperfusion by pulsatile mechanism acting on endothelial cells.

Effects of Recurring IPC vs. rIPC Maneuvers on Exercise Performance, Pulse Wave Velocity, and Red Blood Cell Deformability: Special Consideration of Reflow Varieties

“…This multifactorial condition includes the formation of reactive oxygen species and oxidative stress, calcium overload, and inflammation [ 34 ]. While (r)IPC has been found to reduce I/R injury [ 35 ], the exact mechanism is still debated. It might be reasonable that (r) IPC modulates the production of vasoactive substances including NO [ 10 , 35 ] and oxygen free radicals and reduces the overproduction of ROS [ 36 ], thus providing protection against longer periods of ischemia/reperfusion [ 37 ].…”

“…While (r)IPC has been found to reduce I/R injury [ 35 ], the exact mechanism is still debated. It might be reasonable that (r) IPC modulates the production of vasoactive substances including NO [ 10 , 35 ] and oxygen free radicals and reduces the overproduction of ROS [ 36 ], thus providing protection against longer periods of ischemia/reperfusion [ 37 ]. However, short I/R episodes during (r)IPC, especially those with high reflow conditions, might possibly promote an adverse environment in terms of exercise improvement.…”

Exploration of the effect and mechanism of Shexiang Tongxin Dropping Pill on coronary microvascular dysfunction

“…The adapter protein p66 shc is an integral component of the mitochondrial system that regulates endogenous production of free radicals and apoptosis (Cosentino et al, 2008;Gertz and Steegborn, 2010). It governs a range of cardiovascular pathologies, including endothelial dysfunction, coronary artery disease, and ischemia/reperfusion injuries (Silvia, 2006). Given its control over endothelial ROS and NO production (Costantino et al, 2019), p66 shc is closely associated with coronary microvascular dysfunction.…”