Impact of Dynamic Transmural Pressure on Lymph Propulsion in Lymphatic Vessels

Abstract

Transmural pressure is an important determinant of pumping in collecting lymphatic vessels. Here we studied the impact of dynamic transmural pressure in lymphatic vessels using our physiology‐based computational model [1]. In parallel, we conducted in vitro studies in isolated lymphatic vessels from rat mesentery to examine the effect of dynamic transmural pressure. Vessel segments containing multiple valves were isolated, cannulated, and pressurized at varying levels of inlet and outlet pressures (Pin = Pout, zero transaxial pressure difference). Dynamic pressure waves at different physiologic frequencies (0 – 0.5 Hz) and amplitudes (0 – Pin) were introduced at the inlet and outlet reservoirs. Intraluminal pressure (measured with a servo‐null system) and inner diameter were recorded throughout the experiment. At all pressure amplitudes and frequencies (both higher and lower than normal contraction frequency of the vessel), the dynamic pressure wave was superimposed on the physiologic contraction of the vessel and was detectable in both the intraluminal pressure and diameter traces. The results of our computational model demonstrated that dynamic transmural pressure increased the flow rate at low baseline transmural pressures. Under these circumstances increasing the amplitude and/or frequency of oscillations further facilitated the pumping. Additionally, our computational model enables us to control the transmural pressure by varying external pressure (independent of inlet and outlet pressures). This allows us to study conditions with non‐zero transaxial pressure differences. For example, for an adverse pressure difference of 3 cmH2O and average transmural pressure of 3 cmH2O, average flow rate increased 10% when transmural pressure oscillated with an amplitude of 1 cmH2O; doubling the contraction frequency resulted in a further 15% higher flow rate. These results suggest that dynamic transmural pressure can play an important role in maintaining lymph propulsion in areas of weaker intrinsic pumping activity.Support or Funding InformationGrant support: NIH R01 HL094269, U01 HL123420 (JEM), NIH R01 HL‐120867 (MJD). JEM wishes to acknowledge the support of The Royal Society, The Royal Academy of Engineering, and The Sir Leon Bagrit Trust.