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Peritoneal cavity lavage reduces the presence of mitochondrial damage associated molecular patterns in open abdomen
Patricia A Martinez-Quinones1, Cameron G McCarthy, Caleb J Mentzer
1From the Department of Surgery (P.A.M-Q., S.B.H., K.O.M.), Department of Physiology (C.G.M., C.F.W., R.C.W.), Medical College of Georgia at Augusta University, Augusta, Georgia; and Division of Trauma and Surgical Critical Care (C.J.M.), Miller School of Medicine, University of Miami, Miami, Florida.
Background:
Mitochondrial damage-associated molecular patterns (mtDAMPs), such as mitochondrial DNA and N-formylated peptides, are endogenous molecules released from tissue after traumatic injury. mtDAMPs are potent activators of the innate immune system. They have similarities with bacteria, which allow mtDAMPs to interact with the same pattern recognition receptors and mediate the development of systemic inflammatory response syndrome (SIRS). Current recommendations for management of an open abdomen include returning to the operating room every 48 hours for peritoneal cavity lavage until definitive procedure. These patients are often critically ill and develop SIRS. We hypothesized that mitochondrial DAMPs are present in the peritoneal cavity fluid in this setting, and that they accumulate in the interval between washouts.
Methods:
We conducted a prospective pilot study of critically ill adult patients undergoing open abdomen management in the surgical and trauma intensive care units. Peritoneal fluid was collected daily from 10 open abdomen patients. Specimens were analyzed via quantitative polymerase chain reaction (qPCR) for mitochondrial DNA (mtDNA), via enzyme immunoassay for DNAse activity and via Western blot analysis for the ND6 subunit of the NADH: ubiquinone oxidoreductase, an N-formylated peptide.
Results:
We observed a reduction in the expression of ND6 the day after lavage of the peritoneal cavity, that was statistically different from the days with no lavage (% change in ND6 expression, postoperative from washout: -50 ± 11 vs. no washout day, 42 ± 9; p < 0.05). Contrary to expectation, the mtDNA levels remained relatively constant from sample to sample. We then hypothesized that DNAse present in the effluent may be degrading mtDNA.
Conclusion:
These results indicate that the peritoneal cavity irrigation reduces the presence of mitochondrial DAMPs in the open abdomen. It is possible that increased frequency of peritoneal cavity lavage may lead to decreased systemic absorption of mtDAMPs, thereby reducing the risk of SIRS.
Level Of Evidence:
Prospective study, Case Series, Level V.
Insights
Peritoneal lavage effectively reduces mitochondrial damage-associated molecular patterns (mtDAMPs) in open abdomen patients, potentially lowering the risk of systemic inflammatory response syndrome (SIRS). Further research may explore increased lavage frequency.
Area of Science:
- Immunology
- Critical Care Medicine
- Surgical Innovation
Background:
- Mitochondrial damage-associated molecular patterns (mtDAMPs) are released after injury and activate innate immunity, mimicking bacterial effects.
- These mtDAMPs can trigger systemic inflammatory response syndrome (SIRS), a critical condition in open abdomen management.
- Current open abdomen protocols involve frequent peritoneal lavage, but mtDAMP accumulation between washouts is suspected.
Purpose of the Study:
- To investigate the presence and behavior of mtDAMPs in peritoneal fluid of open abdomen patients.
- To determine if peritoneal cavity lavage influences the levels of mtDAMPs.
- To explore the potential link between mtDAMPs and SIRS development in this patient population.
Main Methods:
- A prospective pilot study involving 10 critically ill adult patients with open abdomens.
- Daily collection of peritoneal fluid for analysis of mitochondrial DNA (mtDNA) and N-formylated peptides (ND6).
- Quantitative PCR, enzyme immunoassay for DNAse activity, and Western blot were employed for specimen analysis.
Main Results:
- Peritoneal lavage significantly reduced the expression of ND6 (an N-formylated peptide) by -50% compared to days without lavage.
- Mitochondrial DNA (mtDNA) levels remained relatively constant, suggesting potential degradation by DNAse in the lavage fluid.
- A statistically significant difference in ND6 expression was observed post-lavage versus no-lavage days (p < 0.05).
Conclusions:
- Peritoneal cavity irrigation is effective in reducing the burden of mtDAMPs within the peritoneal cavity of open abdomen patients.
- The findings suggest that optimizing lavage frequency could mitigate systemic absorption of mtDAMPs.
- This approach may offer a strategy to reduce the incidence or severity of SIRS in critically ill surgical patients.
