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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Autor principal: Anger, Camilla
Formato: First cycle, G2E
Lenguaje:sueco
Inglés
Publicado: 2014
Materias:
Acceso en línea:https://stud.epsilon.slu.se/6673/
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author Anger, Camilla
author_browse Anger, Camilla
author_facet Anger, Camilla
author_sort Anger, Camilla
collection Epsilon Archive for Student Projects
description 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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spelling RepoSLU66732014-09-04T13:56:19Z https://stud.epsilon.slu.se/6673/ Physiological ranges and variability in organ blood flow in laboratory animals Anger, Camilla Animal physiology and biochemistry 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. BAKGRUND: Organblodflöden kan användas vid allometric scaling och i Physiologically Based Pharmakinetic Modeling (PBPK), som kan användas för att extrapolera data från ett djurslag till ett annat. Det har viktiga applikationer inom toxikologiska studier av läkemedelssubstanser och toxiner. För att resultatet från modellerna ska vara så verklighetstrogna som möjligt är det viktigt att ha den naturliga variabiliteten hos försöksdjuren i åtanke. Syftet med literaturstudien är att ge en lättillgänglig sammanställning av de värden som organblodflöden hos de vanligaste försöksdjuren kan variera mellan. METOD: En literatursökning genomfördes i vetenskapliga databaser. Från sökresultaten sammanställdes organblodflödesvärden från review-artiklar och kliniska studier. Från de kliniska studierna användes Baseline- eller kontrollvärden. Endast värden från friska, opåverkade djur togs med. Eftersom det finns viss variation i mätmedor som används i literaturen togs beslut att endast inkludera de mer kända mätmetoderna för att få mer jämförbara värden. Blodflödesvärdena presenteras i enhet ml∙min-1. Viss inkonsekvens råder i nomenklaturen. Framförallt mag/tarmkanalen och leverns blodflödesvärden namnges olika i olika studier. Vid tvekan utelämnades oklart definerat värden från studien. RESULTAT: Blodflödesvärden från samtliga utvalda artiklar sammanställs under resultat. Värden från de största organ från mus, gerbil, hamster, råtta, marmoset, marsvin, kanin, rhesusapa, hund, gris, får och människa presenteras i tabell 1 – 12. De funna intervallen presenteras för alla djurslag i tabell 13. DISKUSSION: Det hade varit önskvärt att ha med fler studier som underlag för vissa av djurslagen (marmoset, gerbil, marsvin). Det hade även varit önskvärt med större variation i studiemetod hos andra djurslag, till exempel studier från både sövda och vakna djur (hund). Det är viktigt att artiklarna har utvärderat sin mätmetod för att eliminera felkällor i mätningen, alla inkluderade artiklar har visat att deras mätmetod är tillförlitlig. Microsphere-tekniken är den vanligaste mätmetoden bland de valda studierna. Hos riktigt små försöksdjur (mus, hamster) kan man ifrågasätta om inte mätmetoden i sig påverkar de fysiologiska blodflödena. Microsphere-tekniken medför kanylsättning i två artärer och isättning av hjärtkateter vilket kan påverka cirkulationen hos djur med små artärer. Variationen hos de funna värdena grundar sig både i biologisk variation i och mellan individer och i variationen som kommer från studieprotokoll, mätteknik, tolkning och beräkningar. 2014-04-22 First cycle, G2E NonPeerReviewed application/pdf sv https://stud.epsilon.slu.se/6673/1/Anger_C_140416.pdf Anger, Camilla, 2014. Physiological ranges and variability in organ blood flow in laboratory animals. First cycle, G2E. Uppsala: (VH) > Dept. of Biomedical Sciences and Veterinary Public Health (until 231231) <https://stud.epsilon.slu.se/view/divisions/OID-713.html> urn:nbn:se:slu:epsilon-s-3687 eng
spellingShingle Animal physiology and biochemistry
Anger, Camilla
Physiological ranges and variability in organ blood flow in laboratory animals
title Physiological ranges and variability in organ blood flow in laboratory animals
title_full Physiological ranges and variability in organ blood flow in laboratory animals
title_fullStr Physiological ranges and variability in organ blood flow in laboratory animals
title_full_unstemmed Physiological ranges and variability in organ blood flow in laboratory animals
title_short Physiological ranges and variability in organ blood flow in laboratory animals
title_sort physiological ranges and variability in organ blood flow in laboratory animals
topic Animal physiology and biochemistry
url https://stud.epsilon.slu.se/6673/
https://stud.epsilon.slu.se/6673/