The Effects of Dexmedetomidine and Remifentanil on Kidney Injury After Muscle Compression Injury in Rats
- Conditions
- Crush InjuryRhabdomyolysisAcute Kidney Injury
- Interventions
- Registration Number
- NCT07094165
- Lead Sponsor
- Ankara City Hospital Bilkent
- Brief Summary
The goal of this interventional preclinical study is to evaluate the potential protective effects of two intravenous anesthetic agents-dexmedetomidine and remifentanil-on kidney function in the context of muscle crush injury, which is known to be a major contributor to acute kidney injury (AKI) following trauma, entrapment, or disasters such as earthquakes. AKI following crush syndrome results from rhabdomyolysis, hypovolemia, oxidative stress, and systemic inflammation, and it significantly increases morbidity and mortality. This study explores whether anesthetic choice during the acute phase of injury influences renal outcomes.
This study used a rat model of crush injury. A total of 28 healthy adult male Wistar rats were randomly divided into four groups (n=7 per group):
1. Control group - no surgical procedure, no injury, no drug.
2. Sham group - anesthesia and cannulation were performed but no crush injury or drug administered.
3. Dexmedetomidine group - crush injury + intravenous dexmedetomidine infusion (3 µg/kg/h) for 1 hour.
4. Remifentanil group - crush injury + intravenous remifentanil infusion (1 µg/kg/h) for 1 hour.
Crush injury was induced by applying a metal clamp with a constant pressure of 3 kg to both gastrocnemius muscles for 2 hours, under anesthesia. After the clamp was removed, animals in the two treatment groups received a one-hour intravenous infusion of their assigned drug. Blood samples were taken at baseline and at 6 hours post-injury. After euthanasia, bilateral kidney tissues were harvested for biochemical and histopathological evaluation.
The main questions this study aimed to answer were:
* Does dexmedetomidine reduce serum and tissue levels of AKI biomarkers (such as NGAL, KIM-1, TIMP-2, IGFBP7) more effectively than remifentanil in a rat model of crush injury?
* Are there histological differences in kidney damage between the treatment groups?
* What is the impact of both drugs on oxidative stress markers (TAC - total antioxidant capacity, TOS - total oxidant status) and renal function parameters such as creatinine and urea?
Biochemical analyses included ELISA-based quantification of NGAL, KIM-1, TIMP-2, IGFBP7, TAC, TOS, serum creatinine, and BUN. Histopathological scoring was performed by a blinded pathologist, assessing tubular necrosis, interstitial edema, and inflammatory cell infiltration.
The study found that rats in the dexmedetomidine group exhibited lower levels of renal injury markers and histopathological damage scores compared to those in the remifentanil group. These findings suggest that dexmedetomidine may offer superior renal protection during acute crush injury compared to remifentanil, potentially via anti-inflammatory and antioxidant mechanisms.
The results of this study may help guide anesthetic drug selection in trauma patients at high risk of kidney injury, and lay the foundation for future translational research.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dexmedetomidine Dexmedetomidine Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion. Dexmedetomidine Laparotomy Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion. Dexmedetomidine Compression Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion. Remifentanil Laparotomy Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion. Remifentanil Remifentanil Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion. Remifentanil Compression Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion. Sham Laparotomy In the sham group, bilateral gastrocnemius muscle compression was applied for 2 hours and laparotomy was performed, but no pharmacological intervention was given. Sham Compression In the sham group, bilateral gastrocnemius muscle compression was applied for 2 hours and laparotomy was performed, but no pharmacological intervention was given.
- Primary Outcome Measures
Name Time Method Serum Creatinine Level Baseline (0 hour), 2 hours, and 6 hours after intervention Change in serum creatinine levels measured at 0, 2, and 6 hours after experimental crush injury in Wistar Albino rats receiving either dexmedetomidine or remifentanil. This outcome is used to assess renal function and the nephroprotective effect of the interventions.
- Secondary Outcome Measures
Name Time Method Histopathological Tubular Injury Score At 6 hours after intervention (after sacrifice) Histopathological evaluation of renal tissue samples using scoring for tubular necrosis, brush border loss, dilatation, congestion, and apoptotic cell count. Quantitative damage scoring was performed blindly by two pathologists to compare the nephroprotective effects of dexmedetomidine and remifentanil.
Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level 0, 2, and 6 hours after intervention NGAL levels measured in serum at three time points to assess early renal tubular injury following experimental crush injury and treatment with dexmedetomidine or remifentanil. NGAL is an early biomarker for acute kidney injury (AKI) and reflects renal stress.
Kidney Injury Molecule-1 (KIM-1) Level 0, 2, and 6 hours after intervention Serum levels of KIM-1 measured by ELISA to evaluate renal tubular epithelial injury and compare the protective effects of the two anesthetic agents.
TIMP-2) × (IGFBP7) Product Level The combined serum levels of TIMP-2 and IGFBP7, representing G1 cell cycle arrest, were measured to detect early renal stress and predict AKI development in the experimental model. 0, 2, and 6 hours after intervention
Trial Locations
- Locations (1)
Ankara Bilkent City Hospital
🇹🇷Ankara, Turkey
Ankara Bilkent City Hospital🇹🇷Ankara, Turkey