Renal Function and Survival are Reduced in a Polytrauma Acute Radiation Injury Rat Model with Extremity Trauma and Hemorrhage

Abstract

The objective of this study was to evaluate whether the presence of radiation injury (RI) decreases survival in an established model of battlefield trauma and hemorrhage in rats. We hypothesized that the addition of radiation to our established traumatic hemorrhage model would increase mortality. Methods: On day zero (D0), male Sprague Dawley rats (n=6/group) received Buprenorphine SR prior to being anesthetized with isoflurane to perform catheterization of a carotid artery. Twenty-four hours later (day 1 or D1), rats were randomly assigned to 1 of 4 groups: 1- sham (no injury; no radiation); 2- RI only; 3- traumatic hemorrhage alone (ET+HEM); or 4- RI combined with traumatic hemorrhage (RI+ET+HEM). For RI and RI+ET+HEM groups, rats were anesthetized and placed inside a cabinet X-ray irradiator (MultiRad 350, Precision, CT) to receive a single sub-lethal X-ray dose of 5.5 Gy, delivered at 1 Gy/min, to induce acute radiation injury. For ET+HEM and RI+ET+HEM groups, under isoflurane, rat then received a unilateral extremity trauma injury. After 90 minutes, a conscious hemorrhage of 37% of the rat estimated blood volume was withdrawn. Rats were monitored for 14 days following injury or sham procedures and provided Buprenorphine SR as needed for pain. Rats remained un-resuscitated and renal function was assessed in vivo by glomerular filtration rate (GFR). GFR was measured with a probe non-invasively and securely strapped to the belly of the rat for about 2.5h. Samples for GFR were collected on D1, day 3 (D3), and day 15 (D15) (or terminal day) from the injury. Result: Sham rats had 100% survival at D15, while RI and ET+HEM rats both had 50% mortality. RI+ET+HEM rats, however, demonstrated 100% mortality by D15; differences in survival proportions were significant (P=0.005). Sham rats showed no significant decrease in GFR (1.0-1.2 ml/min/100g) from D1 to D15. Rats from RI group showed a slight decrease in GFR from D1 to D3 (1.2 to 0.9 ml/min/100g, respectively) at the D3 of measurement. By D15, GFR was 33% lower than D1 in RI group. ET+HEM group showed significant decline in GFR on D1 and D3. However, RI+ET+HEM group showed the most significant decline in GFR ( i.e., >50% lower than sham group on D1 and D3), with little to no improvement over time. Conclusion: We developed a new rodent model of RI+ET+HEM by combining high dose of X-ray irradiation with traumatic hemorrhage, which allows acute (hours) as well as chronic (days) observation. While RI or ET+HEM alone produced significant mortality, the combination of traumatic hemorrhage with RI increased mortality to 100% before D15. Radiation injury combined with extremity trauma and hemorrhage results in significant impairment of renal function. Extremity trauma and hemorrhage impaired renal function more than radiation injury alone. Disclaimer: The views expressed in this abstract are those of the author(s) and do not reflect the offcial policy or position of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government. Supported by Biomedical Advanced Research and Development Authority (BARDA). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.