Persons over 60 years of age are particularly susceptible and vulnerable to septicemia. The mortality rate among septic patients over 60 years of age has been estimated to be more than seven times higher than the mortality rate among septic patients below that age. In spite of these facts, practically no integrated study of the responses of the aging host to sepsis has been reported. Our objective is to characterize the progression of pathophysiological events in the cecal ligation and puncture-induced peritonitis model using mice of different ages. This study is based upon the hypothesis that understanding the progression of events in a rodent peritonitis model will ultimately lead to a definition of the host defect which increases vulnerability with age to invasive pyrogenic infection. The first set of experiments will focus on the lethality of the cecal ligation and puncture method in young (6 mos) and old (24 mos) mice. We will establish the percent cumulative lethality, identify and count aerobic and anaerobic bacteria in the blood and peritoneum, and assay the concentration of endotoxin in plasma in both age groups. A second set of experiments will be designed to assess selected hematologic, metabolic, and endocrine responses in mice of different ages at time zero, in early sepsis, and in late sepsis. The hyperdynamic and hypodynamic phases of sepsis will be defined in the two age groups by their plasma glucose, lactate, and pH and heart rate, respiratory rate, and rectal temperature, assessed every three hours over the course of infection. Subsequent experiments will profile hormonal and metabolic responses in the hyperdynamic and hypodynamic phases and the capacity for glycogenesis and gluconeogenesis in the hypodynamic phase in both age groups. In addition, septic mice will be examined for pathological changes by measuring serum glutamic-pyruvic transaminases and by light microscopic examination of selected fixed and stained tissues. Successful characterization of this aging model will enhance our understanding of (1) the influence of advancing age on the progression and outcome of serious infection and (2) the underlying reasons why the risk of opportunistic infection is amplified with age.
| Hyde, S R; Stith, R D; McCallum, R E (1990) Mortality and bacteriology of sepsis following cecal ligation and puncture in aged mice. Infect Immun 58:619-24 |
