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Hemodynamic and metabolic alterations during experimental sepsis in young and adult rats
P V Pedersen1, B W Warner, H S Bjornson
1Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558.
Insights
Young and adult rats show similar survival and hemodynamic responses to sepsis. However, age-related differences exist in metabolic changes, including glucose levels and resting energy expenditure, following cecal ligation and puncture (CLP) sepsis.
Area of Science:
- Sepsis Pathophysiology
- Comparative Animal Models
- Physiological Responses to Infection
Background:
- Cecal ligation and puncture (CLP) is a widely used preclinical model for sepsis.
- Understanding age-specific responses to sepsis is crucial for developing targeted therapies.
- Limited data exists on the comparative physiological and metabolic effects of sepsis in young versus adult rats.
Purpose of the Study:
- To compare hemodynamic and metabolic alterations in young and adult rats following CLP-induced sepsis.
- To assess differences in survival rates, cardiovascular function, and metabolic markers between age groups.
- To elucidate age-dependent variations in the host response to sepsis.
Main Methods:
- Cecal ligation and puncture (CLP) performed on young (4-6 weeks) and adult (12-14 weeks) rats.
- Determination of 96-hour survival rates.
- Measurement of mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), and resting energy expenditure (REE) at 8 and 16 hours post-CLP.
- Analysis of liver and muscle glycogen levels at 16 hours post-CLP.
- Blood and peritoneal fluid cultures performed.
Main Results:
- Similar mortality rates observed between young and adult rats post-CLP.
- Mean arterial blood pressure (MAP) remained stable with no significant intergroup differences.
- Heart rate (HR) was consistently higher in young rats.
- Adult rats exhibited hyperglycemia, while young rats showed transient hypoglycemia at 8 hours, normalizing by 16 hours.
- Plasma lactate and BUN levels were similar and unchanged during sepsis.
- Both age groups developed hypoaminoacidemia and an increased phenylalanine to tyrosine ratio.
- Resting energy expenditure (REE) was higher in young rats but did not change significantly during sepsis.
Conclusions:
- Sepsis induced by CLP elicits comparable survival and hemodynamic stability in young and adult rats.
- Significant age-dependent metabolic differences are evident, particularly in glucose regulation and baseline energy expenditure.
- These findings highlight the importance of considering age in sepsis research and clinical management.
Abstract:
Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats. It is not known if the response to sepsis is similar in young and adult rats. This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP. In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP. Levels of glycogen in liver and muscle were determined 16 hours after CLP. Mortality rate was similar in young and adult rats. MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats. HR was higher in young rats at all times studied. The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours. Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis. Both young and adult rats became hypoaminoacidemic after CLP. The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups. REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
