Mechanisms by which low-intensity ultrasound improve tolerance to ischemia-reperfusion injury

Abstract

Recent studies show that low-intensity ultrasound (US) increases endothelial nitric oxide (NO) levels in different models both in vitro and in vivo. Ischemia-reperfusion (I/R) injury is characterized by endothelial cell dysfunction, mainly as a result of altered shear stress responses associated with vasoconstriction, reduced capillary perfusion and excessive oxidative stress. This review provides an overview of the microvascular effects of low-intensity US and suggests that US exposure can be a method to provide tolerance to I/R damage. The hamster cheek pouch, extensively used in studies of I/R-induced injury, has been characterized in terms of changes of arteriolar diameter, flow and shear stress. The low-intensity US exposure reduces vasoconstriction and leukocyte adhesion and increases capillary perfusion during postischemic reperfusion. These effects may be the result of enhanced fluctuations in shear stress exerted by the flowing blood on the vessel wall. The fluctuations in turn are due to mechanical perturbations arising from the difference in acoustical impedance between the endothelial cells and the vessel content. We believe that periodic pulses of US may also cause a sustained reduction of oxidative stress and an enhanced endothelial NO level by increasing oscillatory shear stress during postischemic reperfusion. Low-intensity US exposure may represent a safe and novel important therapeutic target for patients with acute coronary syndromes and for treatment of chronic myocardial ischemia.