Mortality and bacteriology of sepsis following cecal ligation and puncture in aged mice

Abstract

Epidemiologic data suggest that elderly adults are more susceptible to invasive bacterial infection by indigenous gut flora than are younger adults. The purpose of this investigation was to characterize a murine model of clinically encountered peritonitis in the aged. We subjected three different age groups (young, 16 weeks; mature, 12 months; senescent, 24 months) of C57BL/6NNia mice to surgically induced peritonitis by the cecal ligation and puncture procedure. Senescent mice died in a significantly shorter time following surgery than mature mice (median time to death, 24.4 versus 38.5 h, respectively; P s 0.001). Blood, liver, spleen and occasionally, ceca were obtained at 2 and 12 h after the cecal ligation and puncture procedure and immediately following death, to characterize the bacterial kinetics of the model. Qualitative and quantitative aerobic, anaerobic, and coliform cultures were performed. No age-related differences were found in the types of bacteria isolated throughout the time course of progressive sepsis. In mice in the mature and senescent age groups, at 2 and 12 h postsurgery, gram-negative anaerobes and gram-positive aerobes predominated in all tissues that were cultured. At the time of death, however, blood and tissue isolates consisted predominately of coliform bacteria. The shift from mixed infection during sepsis to predominantly gram-negative bacterial infection reflected a similar progressive shift in bacterial types found in the cecum. At death, senescent mice had 100-fold fewer coliform bacteria in the bloodstream than those found in mature mice (2.5 x 10' versus 4.6 x 1011, respectively). The increased sensitivity of aged mice to invasive bacterial infection documented in this series of experiments accords well with human epidemiologic experience and demonstrates the appropriateness of the model for continued investigations of sepsis in the aged.

Lipopolysaccharide-tumor necrosis factor-glucocorticoid interactions during cecal ligation and puncture-induced sepsis in mature versus senescent mice

“…CLP surgical procedure. Peritonitis was induced surgically as described previously (20). Briefly, a 1-cm incision was made into the peritoneal cavity, and the cecum was exposed.…”

“…In a previous investigation, we used the cecal ligation and puncture (CLP) procedure to compare age-related differences in lethality of overwhelming bacterial infection (20,44). We found that senescent (24-month-old) C57BL/6NNia male mice subjected to CLP sepsis were more sensitive than mature (12-month-old) mice as manifested by significantly shorter survival times after surgery (means, 24 and 38 h, respectively) and a 100-fold-lower bacterial burden at the time of death.…”

Pathways of renal injury in systemic gram‐negative sepsis

“…The generated cytokine levels and overall physiology of the animals are closer to what is observed in most patients [13,14]. Furthermore, the presence of actual bacteria in the blood as opposed to chemically purified endotoxin somehow changes the pathophysiology of the disease [15]. This is clearly illustrated in the mortality rate of animals with absent TLR4 when subjected to either model [no effect with lipopolysaccharide (LPS) injection but significant mortality with CLP] [16,17].…”

“…The role of specific TLRs should be investigated with caution in CLP as it is essentially a polymicrobial model of sepsis, albeit with a predominance of gram-negative contribution [15]. Nevertheless, and despite technical difficulties that can result in a lack of consistency, this model is gaining increased use because of its superior clinical relevance [10].…”

Azithromycin reduces systemic inflammation and provides survival benefit in murine model of polymicrobial sepsis

“…In both the models, azithromycin neither elevated nor further suppressed the WBC count, thus suggesting it to have no immunosuppressive property. Sepsis is reported to produce hypodynamic state by reducing body temperature and blood glucose (19). Therefore these parameters were measured in all the groups.…”