Physiological ranges and variability in organ blood flow in laboratory animals
BACKGROUND: Organ blood flow rates are useful in allometric scaling and for the application of Physiologically Based Pharmacokinetic Modeling (PBPK). These models are typically used for extrapolating pharmacokinetic data across different species, which has important applications in drug discovery an...
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| Formato: | First cycle, G2E |
| Lenguaje: | sueco Inglés |
| Publicado: |
2014
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| Materias: | |
| Acceso en línea: | https://stud.epsilon.slu.se/6673/ |
| Sumario: | BACKGROUND: Organ blood flow rates are useful in allometric scaling and for the application of Physiologically Based Pharmacokinetic Modeling (PBPK). These models are typically used for extrapolating pharmacokinetic data across different species, which has important applications in drug discovery and safety assessment. Therefore, it is also essential to consider the natural variability in the physiological parameters of animals.
The objective of this literature survey is to provide such data on how organ blood flow rates can vary in our most common laboratory animals.
METHOD: A literature survey was done in scientific databases. Data on organ blood flow rates were compiled from review articles and clinical studies. Primarily blood flow rates from healthy, unaffected animals were included.
Since there is a great variation in measuring techniques, only the most commonly used methods were included to ensure comparability of data across different studies.
Blood flow rates are presented in units of ml∙min-1. Recalculations were done whenever necessary.
There is an inconsistency in nomenclature of organ blood flow rates, particularly of hepatic and gastrointestinal blood flow rates.
RESULTS: Blood flow rates from articles are compiled in the result section. Blood flow rates from major organs and tissues from mouse, gerbil, hamster, rat, marmoset, guinea pig, rabbit, Rhesus monkey, dog, pig, sheep and man are presented in Tables 1-12. Ranges of blood flow rates are presented in Table 13.
DISCUSSION: Since very few studies could be obtained on marmoset, gerbil and guinea pig organ blood flow rates, more studies on these animals are needed. A greater variation of study methods in other species is also desired. Studies on blood flow rates in both conscious and anesthetized animals are needed because anesthetics are commonly used in many pharmacological experiments.
A stringent evaluation of measuring technique is essential for assessment of the validity of data. All studies have taken precautions to eliminate various sources of experimental error.
The microsphere technique is the most common method for measuring organ blood flow. The technique may give misleading blood flow rates in smaller laboratory animals (mouse, hamster) because of its invasiveness. Cannulation of two arteries and catheterization of the heart may affect circulation in animals with smaller arteries.
Variability in organ blood flow rates originate from both biological variations within and between individuals as well as from extrinsic variation due to protocol design, measuring technique and data assessment. |
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