Comparing the Effects of Isoflurane and Alpha Chloralose upon Mouse Physiology

Functional magnetic resonance imaging of mice requires that the physiology of the mouse (body temperature, respiration and heart rates, blood pH level) be maintained in order to prevent changes affecting the outcomes of functional scanning, namely blood oxygenation level dependent (BOLD) measures and cerebral blood flow (CBF). The anesthetic used to sedate mice for scanning can have major effects on physiology. While alpha chloralose has been commonly used for functional imaging of rats, its effects on physiology are not well characterized in the literature for any species. In this study, we anesthetized or sedated mice with isoflurane or alpha chloralose for up to two hours, and monitored physiological parameters and arterial blood gasses. We found that, when normal body temperature is maintained, breathing rates for both drugs decrease over the course of two hours. In addition, alpha chloralose causes a substantial drop in heart rate and blood pH with severe hypercapnia (elevated blood CO2) that is not seen in isoflurane-treated animals. We suggest that alpha chloralose does not maintain normal mouse physiology adequately for functional brain imaging outcome measures.

[1]  J. Mitchell,et al.  The effects of acid-base disturbances on cardiovascular and pulmonary function. , 1972, Kidney international.

[2]  Holzgrefe Hh,et al.  Alpha-chloralose as a canine anesthetic. , 1987 .

[3]  H. Holzgrefe,et al.  Alpha-chloralose as a canine anesthetic. , 1987, Laboratory animal science.

[4]  K. Field,et al.  Anesthesia and surgery of laboratory animals. , 1987, The Veterinary clinics of North America. Small animal practice.

[5]  Andrew N. Rowan,et al.  Biological Effects of Blood Loss: Implications for Sampling Volumes and Techniques , 1989 .

[6]  Society of magnetic resonance in medicine , 1990 .

[7]  M. Ueki,et al.  Effect of alpha‐chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat , 1992, Acta anaesthesiologica Scandinavica.

[8]  J. Silverman,et al.  A review of laboratory animal anesthesia with chloral hydrate and chloralose. , 1993, Laboratory animal science.

[9]  M. Moskowitz,et al.  Cerebrovascular Responses under Controlled and Monitored Physiological Conditions in the Anesthetized Mouse , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  S. Hart,et al.  Clinical and clinicopathological assessment of serial phlebotomy in the Sprague Dawley rat. , 1997, Laboratory animal science.

[11]  Diters Rw,et al.  Clinical and clinicopathological assessment of serial phlebotomy in the Sprague Dawley rat. , 1997 .

[12]  A. Verkman,et al.  Analysis of organ physiology in transgenic mice. , 2000, American journal of physiology. Cell physiology.

[13]  W. Muir,et al.  Handbook of Veterinary Anesthesia , 2000 .

[14]  Robin Hull,et al.  A good practice guide to the administration of substances and removal of blood, including routes and volumes , 2001, Journal of applied toxicology : JAT.

[15]  E. De Schutter,et al.  Comparing BOLD fMRI signal changes in the awake and anesthetized rat during electrical forepaw stimulation. , 2001, Magnetic resonance imaging.

[16]  Afonso C. Silva,et al.  Laminar specificity of functional MRI onset times during somatosensory stimulation in rat , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Dahan,et al.  Influence of anaesthesia and analgesia on the control of breathing. , 2003, British journal of anaesthesia.

[18]  T. Duong,et al.  Echo‐planar BOLD fMRI of mice on a narrow‐bore 9.4 T magnet , 2004, Magnetic resonance in medicine.

[19]  Dirk Nolte,et al.  Long-term anaesthesia using inhalatory isoflurane in different strains of mice—the haemodynamic effects , 2004, Laboratory animals.

[20]  Russell R. Monroe,et al.  The pharmacology of chloralose , 1964, Psychopharmacologia.

[21]  Tadashi Tanaka,et al.  Insulin secretion and glucose utilization are impaired under general anesthesia with sevoflurane as well as isoflurane in a concentration-independent manner , 2005, Journal of Anesthesia.

[22]  C. A. Marsden,et al.  Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats , 2005, Psychopharmacology.

[23]  J. Auwerx,et al.  Collection of Blood and Plasma from the Mouse , 2006, Current protocols in molecular biology.

[24]  Dirk Wiedermann,et al.  A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat , 2006, NeuroImage.

[25]  G. Iannetti,et al.  BOLD functional MRI in disease and pharmacological studies: room for improvement? , 2007, Magnetic resonance imaging.

[26]  Seong-Gi Kim,et al.  Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex. , 2006, Cerebral cortex.

[27]  R. Hoyt,et al.  Chapter 2 – Mouse Physiology , 2007 .

[28]  K. Itoh,et al.  The entry of manganese ions into the brain is accelerated by the activation of N-methyl-d-aspartate receptors , 2008, Neuroscience.

[29]  Jill M. Wetter,et al.  Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI , 2008, British journal of pharmacology.

[30]  Fu-Shan Jaw,et al.  BOLD fMRI mapping of brain responses to nociceptive stimuli in rats under ketamine anesthesia. , 2008, Medical engineering & physics.

[31]  Arend Heerschap,et al.  Isoflurane anesthesia is a valuable alternative for α‐chloralose anesthesia in the forepaw stimulation model in rats , 2009, NMR in biomedicine.

[32]  Andreas Bruns,et al.  Validation of cerebral blood perfusion imaging as a modality for quantitative pharmacological MRI in rats , 2009, Magnetic resonance in medicine.

[33]  Zhifeng Liang,et al.  Mapping resting-state brain networks in conscious animals , 2010, Journal of Neuroscience Methods.

[34]  Pen-Li Lu,et al.  MicroPET imaging of noxious thermal stimuli in the conscious rat brain , 2010, Somatosensory & motor research.

[35]  Craig K. Jones,et al.  Functional networks in the anesthetized rat brain revealed by independent component analysis of resting-state FMRI. , 2010, Journal of neurophysiology.

[36]  Mathias Hoehn,et al.  High field BOLD response to forepaw stimulation in the mouse , 2010, NeuroImage.

[37]  Christakis Constantinides,et al.  Effects of isoflurane anesthesia on the cardiovascular function of the C57BL/6 mouse. , 2011, ILAR journal.

[38]  M. Rudin,et al.  Increased blood oxygen level‐dependent (BOLD) sensitivity in the mouse somatosensory cortex during electrical forepaw stimulation using a cryogenic radiofrequency probe , 2010, NMR in biomedicine.

[39]  M. Catherine Bushnell,et al.  Rodent functional and anatomical imaging of pain , 2012, Neuroscience Letters.

[40]  Kai-Hsiang Chuang,et al.  Optimization of flow‐sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain , 2012, NMR in biomedicine.

[41]  Lynn Uhrig,et al.  Effects of Anesthetic Agents on Brain Blood Oxygenation Level Revealed with Ultra-High Field MRI , 2012, PloS one.

[42]  Alan P. Koretsky,et al.  Early development of arterial spin labeling to measure regional brain blood flow by MRI , 2012, NeuroImage.

[43]  D. Javitt,et al.  Functional connectivity fMRI in mouse brain at 7T using isoflurane , 2013, Journal of Neuroscience Methods.

[44]  J. Klein,et al.  Blood gases and energy metabolites in mouse blood before and after cerebral ischemia: the effects of anesthetics , 2013, Experimental biology and medicine.

[45]  P. Ainslie,et al.  Effect of acute hypoxia on regional cerebral blood flow: effect of sympathetic nerve activity. , 2014, Journal of applied physiology.

[46]  Rafael Delgado y Palacios,et al.  Different anesthesia regimes modulate the functional connectivity outcome in mice , 2014, Magnetic resonance in medicine.

[47]  M. Febo,et al.  Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats , 2014, The international journal of neuropsychopharmacology.

[48]  Kai-Hsiang Chuang,et al.  Neural correlate of resting-state functional connectivity under α2 adrenergic receptor agonist, medetomidine , 2014, NeuroImage.

[49]  Aileen Schroeter,et al.  Optimization of anesthesia protocol for resting-state fMRI in mice based on differential effects of anesthetics on functional connectivity patterns , 2014, NeuroImage.

[50]  S. Houten,et al.  Optimizing anesthetic regimen for surgery in mice through minimization of hemodynamic, metabolic, and inflammatory perturbations , 2014, Experimental biology and medicine.

[51]  Zhifeng Liang,et al.  Neuroplasticity to a single-episode traumatic stress revealed by resting-state fMRI in awake rats , 2014, NeuroImage.

[52]  Kai-Hsiang Chuang,et al.  Detection of functional connectivity in the resting mouse brain , 2014, NeuroImage.

[53]  Aline Seuwen,et al.  Specificity of stimulus-evoked fMRI responses in the mouse: The influence of systemic physiological changes associated with innocuous stimulation under four different anesthetics , 2014, NeuroImage.

[54]  Jyh-Horng Chen,et al.  Repeated BOLD-fMRI Imaging of Deep Brain Stimulation Responses in Rats , 2014, PloS one.

[55]  L. Boorman,et al.  Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime , 2015, Scientific reports.

[56]  P. Kulkarni,et al.  Integration of neural networks activated by amphetamine in females with different estrogen levels: A functional imaging study in awake rats , 2015, Psychoneuroendocrinology.

[57]  Xiao Liu,et al.  Dynamic resting state functional connectivity in awake and anesthetized rodents , 2015, NeuroImage.

[58]  Wen-Ju Pan,et al.  Different dynamic resting state fMRI patterns are linked to different frequencies of neural activity. , 2015, Journal of neurophysiology.

[59]  Bruce R. Rosen,et al.  Layer-specific interhemispheric functional connectivity in the somatosensory cortex of rats: resting state electrophysiology and fMRI studies , 2015, Brain Structure and Function.