Hemorrhagic shock leads to cell and tissue swelling and no reflow from compressed capillaries. Cell impermeants, including polyethylene glycol-20,000 (PEG-20k), reverse ischemia-induced cell swelling, extend low volume resuscitation (LVR) time after shock, and increase tolerance to the low volume state. The purpose of this study was to explore the mechanisms of action of PEG-20k containing LVR solutions. We hypothesized that PEG-20k acts as both an oncotic agent and an impermeant in the microcirculation, which moves water out of the extracellular space and into the capillaries to affect peripheral capillary filling and enhanced perfusion during the low volume state. Rats were hemorrhaged until arterial lactate reached 9-10 mM/L. Then, saline-based LVR solutions containing various impermeant materials were administered (10% blood volume). The LVR times for these solutions was determined by measuring the amount of time required for plasma lactate to climb back to 9-10 mM after LVR administration (low volume tolerance). Capillary blood flow was measured by colored microspheres and blood volume was measured by FITC-labeled albumin dilution. Gluconate (impermeant), albumin (colloid), and PEG-20k (hybrid) increased LVR time over saline by 4-, 3-, and 8-fold, respectively. The combination of impermeant + albumin produced a biological effect that was similar to PEG-20k alone. Capillary blood flow and plasma volume was decreased after shock with saline LVR but increased with PEG-20k, relative to saline. These data are consistent with the hypothesis that PEG-20k may act by establishing multiple osmotic gradients in the microcirculation to drive cell-to-capillary water transfer during hypovolemic shock.
- The American Society for Pharmacology and Experimental Therapeutics