Abstract
Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.
Highlights
Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research
The ECG of SPF animals showed a range of abnormal cardiac rhythms including premature ventricular contractions, salvos and bigeminy episodes (Fig. 2a,b)
Arrhythmias were found in 85% of SPF animals (17/20) compared to no arrhythmias in the conventional rats (p < 0.001) (Table 1)
Summary
Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Most animal husbandry facilities adopt this specific-pathogen free (SPF) approach and provide certification that a colony or breeding pair is free from common infectious agents that a species is customarily exposed to in the wild. This approach has additional benefits of cost-saving and ethical benchmarks as it reduces the number of animals used within individual studies. The physiological variables included decreased tolerance to anesthesia, hemodynamic instability, aberrant hematology, traumatic bleeding and reduced physiological reserve in SPF animals This altered phenotype to the stress of surgical trauma was completely reversed when animals were returned to the original conventional facility
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