Objective: To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic and muscle function Design: Randomized controlled animal study
Setting: University research laboratory
Subjects: Male Wistar ratsInterventions: Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline.
Measurements and Main Results:Following intervention, rats were followed for up to two weeks.Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g. MAFbx, MURF1, myostatin) had peaked on days 2-4 but had normalized by Day 7. Treadmill exercise capacity, forelimb grip strength and in vivo maximum tetanic force were also reduced. Food intake was minimal until Day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6h) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum IL-6 level peaked at 6h but had normalized by Day 2 whereas IL-10 remained persistently elevated and HDL cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by Day 7.Conclusions: This detailed physiological, metabolic, hormonal, functional and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function.