A solution of high concentration albumin has been used for temporal volume expansion when timely resuscitation was unavailable after hemorrhagic shock. However, during prolonged hemorrhagic shock, cell edema and interstitial dehydration can occur and impede the volume expansion effect of albumin. Polyethylene glycol-20K (PEG) can establish an osmotic gradient from swollen cells to capillary lumens and thus facilitate capillary fluid shift and volume expansion. We hypothesized that with similar osmolality, 7.5% PEG elicits more rapid and profound compensatory responses after hemorrhagic shock than 25% albumin. Rats were randomized into three groups (n = 8/group) based on treatment: saline (vehicle), PEG (7.5%), and albumin (25%). Trauma was induced in anesthetized rats with muscle injury and fibula fracture, followed by pressure-controlled hemorrhagic shock (MAP = 55 mm Hg) for 45 min. Animals then received an intravenous injection (0.3 mL/kg) of saline, PEG, or albumin. MAP, heart rate, blood gases, hematocrit, skeletal muscle capillary flow, renal blood flow, glomerular filtration rate, urinary flow, urinary sodium concentration, and mortality were monitored for another 2 hours. Polyethylene glycol-20K and albumin both improved MAP, renal and capillary blood flow, and renal oxygen delivery, and decreased hyperkalemia, hyperlactatemia, hematocrit, and mortality (saline: 100% PEG: 12.5%; albumin: 38%) over saline treatment. Compared with albumin, PEG had a more rapid decrease in hematocrit and more profound increases in MAP, diastolic pressure, renal blood flow, glomerular filtration rate, and urinary flow. These results suggest that PEG may be a better option than albumin for prolonged prehospital care of hemorrhagic shock.

A focus of combat casualty care research is to develop treatment where full resuscitation after hemorrhage is delayed. However, animal models of combat-related hemorrhagic shock in which to determine physiological outcomes of such delays and explore potential treatment for golden hour extension are lacking. In this study, we filled this knowledge gap by establishing a traumatic shock model with reproducible development of AKI and shock-related complications determined by the time of resuscitation.

Acute limb ischemia (ALI) is a sudden lack of blood flow to a limb, primarily caused by arterial embolism and thrombosis. Various experimental animal models, including non-invasive and invasive methods, have been developed and successfully used to induce limb ischemia-reperfusion injuries (L-IRI). However, there is no consensus on the methodologies used in animal models for L-IRI, particularly regarding the assessment of functional recovery. The present study aims to compare different approaches that induce L-IRI and determine the optimal animal model to study functional limb recovery. In this study, we applied a pneumatic cuff as a non-invasive method and ligated the aorta, iliac, or femoral artery as invasive methods to induce L-IRI. We have measured grip strength, motor function, creatine kinase level, inflammatory markers such as nuclear factor NF-κB, interleukin-6 (IL-6), hypoxia markers such as hypoxia-induced factor-1$\mathsf{\alpha }$ (HIF-1$\mathsf{\alpha }$), and evaluated the muscle injury with hematoxylin and eosin (H&E) staining in Sprague Dawley rats after inducing L-IRI. The pneumatic pressure cuff method significantly decreased the muscle strength of the rats, causing the loss of ability to hold the grid and inducing significant limb function impairment, while artery ligations did not. We conclude from this study that the tourniquet cuff method could be ideal for studying functional recovery after L-IRI in the rat model.

In both civilian and military settings, severe hemorrhage rarely occurs in the absence of tissue trauma, yet many animal models for the study of hemorrhage do not include significant tissue trauma. This study using conscious unrestrained rats clearly demonstrates that extremity trauma worsens the probability of survival after a severe hemorrhage. Although no single cardiorespiratory factor accounted for the increased mortality, multiple modest time-related cardiorespiratory responses to the trauma were observed suggesting that their combined dysfunction may have contributed to the reduced survival.

Extremity trauma, including ischemia (e.g., prolonged tourniquet application or crush), is common among battlefield injuries. Injured muscle releases toxins leading to rhabdomyolysis and, potentially, acute kidney injury (AKI). The goal of this study was to characterize sequelae of ischemic extremity injury over 72 h, focusing on time courses of rhabdomyolysis and AKI. Male Sprague Dawley rats were placed into two groups. Ischemic injury was produced in anesthetized rats using bilateral tourniquets (TK; n = 10) for 5 h; control (CON; n = 9) rats were treated identically without TK application. Indicators of rhabdomyolysis and renal function were measured in conscious rats 1 day preinjury (baseline, BL) and then at 1.5, 24, 48, and 72 h post-TK release. Prolonged TK application produced necrosis in both muscle and bone marrow but not in kidney. The wet/dry weights indicated edema in injured limbs at 72 h (4.1 (0.5) (TK) vs. 2.9 (0.1) (CON); p < 0.001). TK rats exhibited a 100-fold increase in creatine kinase activity compared to CON at 1.5 h (20,040 (7265) U/L vs. 195 (86) U/L (mean (SD); p < 0.0001). TK decreased the mean glomerular filtration rate (GFR; p < 0.001) at 1.5 h, but these values recovered by 24 h in concert with elevated urinary flow and alkalinization. Prolonged ischemic extremity injury therefore produced severe rhabdomyolysis without irreversible renal damage.

Editorial: Shock and resuscitation