Penetrating abdominal trauma is caused most commonly by gunshot wounds or stab wounds. As the liver takes up a large proportion of the abdominal cavity, up to 30% of penetrating abdominal trauma causes a liver damage (16). Other organs that commonly involved are small and large bowel and vascular structures (16–18).
Mortality from penetrating abdominal trauma is caused by hemorrhage in the short term and sepsis and multi organ failure at the long term (19–22). In the current study we show in a swine model that injection of VLVG into the abdominal cavity after abdominal injury maintained the animals stable and improved important variables in the serum signifying lower degree of organ damage.
Such a model would allow a means to develop and test novel hemostatic agents for the treatment of intra-abdominal bleeding on the battlefield.
In order to establish a valid trauma model, one must demonstrate change in several parameters that reflect the degree of organ damage and shock. Those parameters include hemodynamics, blood biochemical profile, endocrine profile and in our model also markers of hepatic tissue damage (23–26). Also histopathologic samples from liver tissues in a setting of shock demonstrate certain changes such as central lobular necrosis (27). Our model demonstrated changes in all those parameters, thus making it an appropriate model for trauma, hemorrhagic shock and liver damage. Although hemorrhagic shock was induced, the degree of damage was not sufficient to inflict mortality and therefore we could not conclude from this study whether VLVG improved survival. Hemodynamic monitoring revealed lower HR and higher blood pressure values (SBP, DBP, and MAP) in the VLVG–treated animals. Since hemodynamic parameters represent the degree of hemorrhagic shock, our results suggest that animals treated with alginate had lower levels of shock.
In our study we compared treatment with intraperitoneal saline and intraperitoneal VLVG alginate after inflicting trauma to the liver. On our previous studies we showed in 2 murine models the beneficial effect of VLVG (14, 15). These studies demonstrated that the effect of this specific low molecular alginate is not merely physical. These studies also demonstrated that VLVG specifically had effects than other forms of alginates due to different biochemical properties leading better absorption through membranes. Thus, we assumed that VLVG will have a protective effect of all abdominal organs, especially the liver. For example, cortisol levels may rise causing rise in blood glucose levels due to glycogenolysis gluconeogenesis and insulin resistance (28). In our study reduced levels of glucose and cortisol suggest lower degree of physiologic stress in VLVG-treated animals. Although this effect may be due to lower bleeding, it can also imply of anti-inflammatory effect of VLVG. Another biochemical marker for shock is lactate. Lactate is formed in anaerobic metabolism when tissues lack of oxygen due to circulatory failure as in shock, i.e. lactate is a marker for tissue hypoperfusion (29). In our study the mean blood levels of lactate were reduced in the VLVG-treated group, suggesting better tissue perfusion. Fibrinogen, a marker for hemostasis, is a substrate for clot formation, and is known to be low following trauma with massive hemorrhage due to its consumption. Furthermore, lower levels of fibrinogen after hemorrhage are associated with worse outcomes (30, 31). In our study alginate treated animals showed constantly higher levels of fibrinogen suggesting less activation of the coagulation cascades, adding to its ratification that alginate has hemostatic properties.
Trauma is a multi-organ disease that might cause damage distinct organs such as the kidneys. Acute renal failure is common in major trauma and caused by renal hypoperfusion, or late consequences such as rhabdomyolysis or abdominal compartment syndrome. Acute renal failure is represented by serum creatinine concentration (32, 33). In our study at all-time points creatinine levels were lower in the alginate treated group compared to the control group. This may also point that VLVG-treated animals had lower degree of hemorrhage and hypovolemia due to improved hemostasis.
The levels of liver enzymes are well known to correlate with the degree of liver damage in various diseases including trauma (34, 35). In our study the levels of ALT, AST and LDH were higher in the control group when monitoring ended, suggesting prevention of liver injury by VLVG. Importantly, ALT levels were higher in the control group even before infliction trauma. This was caused due to idiopathic preliminary elevation of ALT in two out of four animals in the control group. When histopathologic analysis was done, samples from VLVG- treated groups showed lesser amount of damage at the middle and final hours of the study; although at the beginning the damage within this group was higher. This further suggests the hepatic preserving properties of VLVG.
Our study has several limitations. It was conducted on a total of only 7 animals. This small number did not allow sufficient power for statistical significance. Therefore we used higher cutoffs for p value and comparison of tendency in order to demonstrate the effect of alginate. In addition, due to ethic limitations the length of observation in our study was rather short thus not allowing assessment of survival and long term effects of VLVG.
In conclusion, this small, proof-of-concept study showed that treatment with alginate, specifically VLVG, ameliorated the effects of penetrating abdominal trauma in pigs. Treatment with VLVG improved hemodynamic measures and showed improved metabolic status in lower degree of intra-abdominal organs damage. Further, larger studies are warranted to corroborate these findings.
List of abbreviations: VLVG -Very Low Viscosity (high) G alginate, SBP-Systolic blood pressure, DBP- diastolic blood pressure, MAP- mean arterial pressure, WBC-white blood cells, RBC- red blood cells, LDH-lactate dehydrogenase, ALT- alanine aminotransferase, AST- aspartate aminotransferase.