Regulation of adventitial interstitial fluid circulation by heartbeat and respiration

Abstract

AbstractA growing body of evidence suggest that the interstitial fluid (ISF) may flow over long distance in the body. In this study, we aim to clarify the potential pathways of adventitial ISF flow and its regulatory mechanisms in rats with improved imaging methods. Fluorescent stereomicroscopy showed that each dilation or contraction of the heart and lungs can generate a to-and-fro motion of the adventitial ISF along the femoral veins following adventitial administration of Fluorescein sodium. Speckle tracking velocimetry revealed a positive regulation of the adventitial ISF flow by the heart rate under physiological conditions. Moreover, the ISF flow rate increased when breath was holding, and a pulsed ISF flow occurred during heavy breathing. In addition, silver nitrate was administered by adventitial or intravenous injection and spectral micro-computed tomography was adopted to compare the pathways of ISF or blood circulation, respectively. Our results indicated that the heart and lungs work synergistically to regulate the adventitial ISF flowing centripetally to the epicardium and myocardium, then into the lungs via pulmonary arteries and return to the heart via pulmonary veins, forming an adventitial ISF circulation. The adventitial ISF circulatory pathway might be a potentially novel route for organ-targeted extravascular drug delivery.