Hypertonic Saline Modulation of Intestinal Tissue Stress and Fluid Balance

Abstract

Crystalloid-based resuscitation of severely injured trauma patients leads to intestinal edema. A potential mechanism of intestinal edema-induced ileus is a reduction of myosin light chain phosphorylation in intestinal smooth muscle. We sought to determine if the onset of edema initiated a measurable, early mechanotransductive signal and if hypertonic saline (HS) can modulate this early signal by changing intestinal fluid balance. An anesthetized rat model of acute interstitial intestinal edema was used. At laparotomy, the mesenteric lymphatic was cannulated to measure lymph flow and pressure, and a fluid-filled micropipette was placed in the intestinal submucosa to measure interstitial pressure. Rats were randomized into four groups (n=6 per group): sham, mesenteric venous hypertension+80 mL/kg 0.9% isotonic sodium chloride solution (ISCS 80), mesenteric venous hypertension+80 mL/kg 0.9% ISCS+4 mL/kg 7.5% saline (ISCS 80+HS), or 4 mL/kg 7.5% saline (HS alone) to receive the aforementioned intravenous fluid administered over 5 min. Measurements were made 30 min after completion of the preparation. Tissue water, lymph flow, and interstitial pressure were measured. Resultant applied volume induced stress on the smooth muscle (sigmaravi-muscularis) was calculated. Mesenteric venous hypertension and crystalloid resuscitation caused intestinal edema that was prevented by HS. Intestinal edema caused an early increase in intestinal interstitial pressure that was prevented by HS. Hypertonic saline did not augment lymphatic removal of intestinal edema. sigmaravi-muscularis was increased with onset of edema and prevented by HS, paralleling the interstitial pressure data. Intestinal edema causes an early increase in interstitial pressure that is prevented by HS. Prevention of the edema-induced increase in interstitial pressure serves to blunt the mechanotransductive signal of sigmaravi-muscularis.

Passive Pressure–Diameter Relationship and Structural Composition of Rat Mesenteric Lymphangions

“…SHG and TPF signal components were imaged and segmented simultaneously to obtain images of fibrillar collagen (types I and III) and elastin, respectively. 18,19 The resolution of the NLOM was between 0.4 and 0.5 lm.…”

Biphasic Regulation of Myosin Light Chain Phosphorylation by p21-activated Kinase Modulates Intestinal Smooth Muscle Contractility

“…The stretching protocols utilized in these studies incorporate data from the in vivo intestinal edema model, including increased mechanical stress measured during edema development and spontaneous contraction frequency and amplitude measured in the organ bath system (7,11,14). Although we have attempted to reproduce the increased stretch that occurs during edema development in intestinal smooth muscle, intestinal edema is a complex phenomenon, and we cannot completely reproduce the effects of edema in a cell model.…”

“…1A) (FX-4000 TM Tension System, Flexcell, Hillsborough, NC). The cyclical stretch protocols were designed using the spontaneous contraction amplitude and frequency measured in vivo in previous experiments (11). Control cells were subjected to basal cyclical stretch consisting of 0.4-Hz sinusoidal strain with a minimum 1% and a maximum 3% elongation (control cyclical stretch (CCS)), mimicking basal spontaneous contractions.…”

“…1B), mimicking non-edematous and edematous conditions in vivo (11). We first determined the time course of MLC phosphorylation changes after cells were subjected to CCS or ECS.…”

“…Intestinal edema develops under various pathologic conditions, such as trauma with fluid resuscitation, abdominal surgery, heart failure, or traumatic brain injury (8 -10). Intestinal edema causes a 6-fold increase in strain in the smooth muscle layer of the intestine compared with non-edematous tissue (11). This increased strain, resulting in increased stretching force to the intestinal smooth muscle cells, is associated with decreased intestinal contractile activity via decreased myosin light chain (MLC) 2 phosphorylation (12)(13)(14)(15).…”