Tonicity and colloid osmotic pressure drive microvascular recovery from low volume hypotensive resuscitation from hemorrhagic shock

Hypertonic saline solution containing 7.5% sodium chloride provides rapid intravascular volume expansion during severe hypovolemic shock, reducing the total fluid required to restore perfusion. Unlike traditional large-volume crystalloid resuscitation, which dilutes circulating blood components, hypertonic saline mobilizes intracellular and interstitial fluids into the vascular space, improving perfusion with minimal infusion volume. This strategy is particularly valuable in military and emergency settings where rapid stabilization and limited fluid availability are critical. In this study, we integrated ex vivo rheological analyses and in vivo microvascular measurements to elucidate the mechanisms underlying low-volume resuscitation with hypertonic saline. In a rheological perspective, using controlled shear flow conditions ranging from 1 to 1,000 s^-1, oscillatory amplitude sweeps (0.002-2.0 Pa at 0.5 Hz), and low-shear aggregation assays, we characterized the interaction of hypertonic saline with common resuscitation fluids, Lactated Ringer's and 5% human serum albumin. Following ex vivo investigation, severe hemorrhagic shock was induced in Golden Syrian hamsters, instrumented with dorsal window chamber to quantify the microhemodynamics, by controlled withdrawal of 50% blood volume, followed by 30 min of hypovolemic shock. At the conclusion of the hypovolemia period resuscitation consisted of an initial infusion of hypertonic saline equal to 3.5% of blood volume, followed by either Lactated Ringer's solution or 5% human serum albumin at 10% of animal's blood volume. Microhemodynamics were assessed over 60 min following resuscitation. Resuscitation with hypertonic saline followed by human serum albumin produced the most favorable microcirculatory outcomes, enhancing arteriolar blood flow and functional capillary density compared to Lactated Ringer's solution. This combination increased reversible red blood cell aggregation and blood rheological changes, which may promote plasma skimming in small arterioles and improved red cell flux in the microcirculation. Although systemic recovery of mean arterial pressure and heart rate was incomplete, blood gas parameters significantly improved, indicating the benefits of effective microvascular reperfusion from severe hypovolemic conditions.