Prolonged Exposure to Intestinal Edemagenic Stress Decreases Mesenteric Lymphatic Contractility
Authors: Harlow Rebecca C. , Singh Reetu , Bagher Pooneh , Heaps Cristine L. , Stewart Randolph H. , Dongaonkar Ranjeet M. 
Published: May 2022

Mesenteric lymphatic vessels (MLVs) are the primary route for removal of excess intestinal interstitial fluid. Lymphatic pumping, the virtue of the intrinsic contractility of lymphatic muscle, is necessary for active lymph transport to the venous circulation and thus resolution of interstitial edema. Acute exposure to edemagenic stress has been reported to increase contractility and pumping of MLVs. However, our recent studies revealed that when exposure to edemagenic stress is prolonged, lymphatic contraction frequency decreases and pump failure ensues. It is unknown how the ability of lymphatic muscle to generate active tension is affected in these maladapted MLVs. Therefore, the purpose of the present study was to evaluate our hypothesis that prolonged exposure to edemagenic stress decreases lymphatic muscle contractility.

Male Sprague Dawley rats underwent midline laparotomy with 3‐day exposure to either venous hypertension (VHT; induced by coarctation of superior mesenteric vein), fluid overload (HD; induced by daily IV infusion of 80 ml/kg lactated Ringer’s saline), or neither (SHAM; no additional intervention). In isometric biomechanics studies, MLVs were mounted on a wire myograph and perfused with warm APSS. Vessel rings were incrementally stretched, stimulated with substance P (1 µM) in 60 mM K+‐APSS (SP K‐APSS), followed by wash out with APSS. This sequence was repeated and the following steady state tensions were recorded at each level of stretch: unstimulated total tension (passive stretch, in APSS), stimulated total tension (SP K‐APSS), and passive tension (Ca++‐free APSS, at the end of the experiment). The circumferential length at the level of stretch yielding optimal delta tension (= stimulated total tension ‐ unstimulated total tension) for each vessel was identified as Lmax. Additionally, unstimulated active tension (= unstimulated total tension ‐ passive tension) and stimulated active tension (= stimulated total tension ‐ passive tension) were calculated.

Vessels from VHT and SHAM groups yielded nearly identical length‐tension relationships. However, compared to SHAM and VHT vessels, HD vessels generated significantly lower tension across all indices: unstimulated total tension, stimulated total tension, passive tension, unstimulated active tension, and stimulated active tension. At optimal stretch (Lmax), the delta tension was lower in HD vessels than SHAM or VHT vessels.

Consistent with findings of the previous studies, prolonged exposure to intestinal edemagenic stress induced mesenteric lymphatic pump failure in VHT and HD vessels. However, lymphatic muscle contractility was reduced only in HD vessels. Taken together, these findings suggest that peri‐ and post‐oprative fluid therapy in major surgery patients receiving fluid therapy may lead to mesenteric lymphatic maladaptation. The consequential decrease in intestinal lymph drainage would then contribute to delayed resolution of intestinal edema, increased morbidity and extended hospital stays.