Indices of Organ Damage after Surviving Hemorrhage and Prolonged Hypotension
Authors: Hinojosa‐Laborde Carmen , Shade Robert , Frost Patrice , Dutton John , Muniz Gary , Hudson Ian L. , Carter Robert , Ryan Kathy 
Published: June 2021

BACKGROUND

Hypotensive resuscitation to raise systolic pressure to 80–90 mm Hg is the standard of care on the battlefield for hemorrhaging Soldiers, and is maintained until the casualty is transported to a surgical unit usually within one hour of injury. Prompt evacuations may not be possible in future conflicts, and hypotension will be required for longer periods of time. This study determined the long‐term effects of prolonged hypotension (PH) held for 0, 1, 2 and 3 hours on kidney, liver and muscle damage up to 21 days after PH, and tested the hypothesis that longer duration of hypotension after hemorrhage will result in greater organ damage.

METHODS

Male baboons were anesthetized and hemorrhaged until systolic blood pressure was 70 mmHg for 10 min. Systolic blood pressure of greater than 80 mm Hg with autologous blood was maintained for 1 hour (1hr PH; n=5), 2 hours (2hr PH; n=5), or 3 hours (3hr PH; n=5) hours. After the PH period, the hemorrhage volume of whole blood was replaced, and the animal was recovered and monitored for 21 days. Control animals were anesthetized, hemorrhaged and immediately resuscitated with hemorrhaged blood (0hr PH, n=3). Blood samples were obtained before and 1, 3, 7, 14 and 21 days after PH, and analyzed for blood chemistry profile. Data were analyzed with 2 way repeated measures ANOVA and Holm‐Sidak test, and expressed as Mean ± Standard Deviation.

RESULTS

Plasma creatinine and blood urea nitrogen were unaffected by PH and remained within normal limits in all PH groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) values were significantly elevated after PH (time effect; P<0.001; PH group effect; P=0.3). Maximum ALT levels were observed on Day 1 after PH in 0hr PH (140 ± 56 U/L), 1hr PH (170 ± 130 U/L), 2hr PH (322 ± 241 U/L), and 3hr PH (387 ± 167 U/L). Maximum AST levels were observed on Day 1 after PH in 0hr PH (218 ± 44 U/L), 1hr PH (354 ± 219 U/L), 2hr PH (515 ± 424 U/L), and 3hr PH (711 ± 278U/L). Maximum CPK values were observed on Day 1 after PH in 0hr PH (7834 ± 3681 U/L), 1hr PH (24336 ± 22268 U/L), 2hr PH (50494 ± 67653 U/L), and 3hr PH (59857 ± 32408 U/L). Maximum LDH values were observed on Day 1 after PH in 0hr PH (890 ± 396 U/L), 1hr PH (2055 ± 1520 U/L), 2hr PH (3992 ± 4895 U/L), and 3hr PH (4771 ± 1884 U/L). Max levels of ALT, AST, CPK, and LDH were positively correlated with the duration of PH (P<0.05). All values returned to pre‐PH levels by 21 days after PH.

CONCLUSIONS

These results indicate that PH up to 3 hours in duration results in transient liver and muscle damage that is correlated with the duration of PH in male baboons. PH of any duration produced minimal effects on the kidney. More studies are needed to determine if longer periods of PH result in permanent and more extensive organ damage.

Support or Funding Information

This study was funded by the United States Army, Medical Research and Materiel Command

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.