A novel, non-invasive method of respiratory monitoring for use with stereotactic procedures

Accurate monitoring of respiration is often needed for neurophysiological studies, as either a dependent experimental variable or an indicator of physiological state. Current options for respiratory monitoring of animals held in a stereotaxic frame include EMG recordings, pneumotachograph measurements, inductance-plethysmography, whole-body plethysmography (WBP), and visual monitoring. While powerful, many of these methods prevent access to the animal's body, interfere with experimental manipulations, or require deep anesthesia and additional surgery. For experiments where these issues may be problematic, we developed a non-invasive method of recording respiratory parameters specifically for use with animals held in a stereotaxic frame. This system, ventilation pressure transduction (VPT), measures variations in pressure at the animal's nostril from inward and outward airflow during breathing. These pressure changes are detected by a sensitive pressure transducer, then filtered and amplified. The output is an analog signal representing each breath. VPT was validated against WBP using 10% carbon dioxide and systemic morphine (4mg/kg) challenges in lightly anesthetized animals. VPT accurately represented breathing rate and tidal volume changes under both baseline and challenge conditions. This novel technique can therefore be used to measure respiratory rate and relative tidal volume when stereotaxic procedures are needed for neuronal manipulations and recording.

[1]  P. Dyck,et al.  A simple method for rat endotracheal intubation. , 1991, Laboratory animal science.

[2]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[3]  A. Beckett,et al.  AKUFO AND IBARAPA. , 1965, Lancet.

[4]  M. Heinricher,et al.  Physiological basis for inhibition of morphine and improgan antinociception by CC12, a P450 epoxygenase inhibitor. , 2010, Journal of neurophysiology.

[5]  D. Woodrum,et al.  Application of the hot-wire anemometer to respiratory measurements in small animal. , 1976, Journal of applied physiology.

[6]  G. Holstege,et al.  Midbrain and medullary control of postinspiratory activity of the crural and costal diaphragm in vivo. , 2011, Journal of neurophysiology.

[7]  F. Leuven,et al.  Raphé tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: Possible implications for tauopathies and Alzheimer's disease , 2011, Respiratory Physiology & Neurobiology.

[8]  Fadi Xu,et al.  Activation of opioid micro-receptors in medullary raphe depresses sighs. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  J. Grønlund,et al.  Evaluation of a constant-temperature hot-wire anemometer for respiratory-gas-flow measurements , 1979, Medical and Biological Engineering and Computing.

[10]  S. Greenfield,et al.  Design and evaluation of a low-cost respiratory monitoring device for use with anaesthetized animals , 2009, Laboratory animals.

[11]  A Eberhard,et al.  Evaluation of respiratory inductive plethysmography: accuracy for analysis of respiratory waveforms. , 1997, Chest.

[12]  G. Olsen,et al.  Respiratory effects of chronic in utero methadone or morphine exposure in the neonatal guinea pig. , 2008, Neurotoxicology and teratology.

[13]  F. van Leuven,et al.  Upper Airway Dysfunction of Tau-P301L Mice Correlates with Tauopathy in Midbrain and Ponto-Medullary Brainstem Nuclei , 2010, The Journal of Neuroscience.

[14]  F. Palec̆ek Measurement of ventilatory mechanics in the rat. , 1969, Journal of applied physiology.

[15]  Melanie R. Bernard,et al.  Widespread spatial integration in primary somatosensory cortex , 2008, Proceedings of the National Academy of Sciences.

[16]  M. Weinger,et al.  Alterations in diaphragm EMG activity during opiate-induced respiratory depression. , 1995, Respiration physiology.

[17]  J. Greer,et al.  PreBötzinger Complex Neurokinin-1 Receptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression , 2011, The Journal of Neuroscience.

[18]  R. Stornetta,et al.  Control of Breathing by Raphe Obscurus Serotonergic Neurons in Mice , 2011, The Journal of Neuroscience.

[19]  M. Heinricher,et al.  GABA-mediated inhibition in rostral ventromedial medulla: role in nociceptive modulation in the lightly anesthetized rat , 1991, Pain.

[20]  G. Cumming The Body Plethysmograph , 1961 .

[21]  D. Altman,et al.  Agreement Between Methods of Measurement with Multiple Observations Per Individual , 2007, Journal of biopharmaceutical statistics.

[22]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[23]  A. Morel,et al.  Tonotopic organization in the medial geniculate body (MGB) of lightly anesthetized cats , 2004, Experimental Brain Research.

[24]  Baruch Krauss,et al.  Microstream Capnography Technology: A New Approach to an Old Problem , 1999, Journal of Clinical Monitoring and Computing.

[25]  D. Altman,et al.  Measuring agreement in method comparison studies , 1999, Statistical methods in medical research.

[26]  J. H. Comroe,et al.  A rapid plethysmographic method for measuring thoracic gas volume: a comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects. , 1956, The Journal of clinical investigation.

[27]  J. Orem,et al.  Medullary respiratory neuronal activity during augmented breaths in intact unanesthetized cats. , 1993, Journal of applied physiology.

[28]  A. Bartolo,et al.  Description and validation of a technique for the removal of ECG contamination from diaphragmatic EMG signal , 2007, Medical and Biological Engineering and Computing.

[29]  F. Sharbrough,et al.  The Cerebral and Systemic Effects of Movement in Response to a Noxious Stimulus in Lightly Anesthetized Dogs Possible Modulation of Cerebral Function by Muscle Afferents , 1994, Anesthesiology.

[30]  J P Jacky,et al.  A plethysmograph for long-term measurements of ventilation in unrestrained animals. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[31]  E. Bar-Yishay,et al.  Whole-body plethysmography. The human factor. , 2009, Chest.

[32]  M. Heinricher,et al.  Neural basis for improgan antinociception , 2010, Neuroscience.

[33]  N. Mellen,et al.  Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons , 2001, Nature Neuroscience.

[34]  P. Mason,et al.  Serotonergic raphe magnus cell discharge reflects ongoing autonomic and respiratory activities. , 2007, Journal of neurophysiology.

[35]  C. Lundgren,et al.  Whole-body plethysmography, does it measure tidal volume of small animals? , 1998, Canadian journal of physiology and pharmacology.

[36]  R. Brosnan,et al.  Assessment of halothane and sevoflurane anesthesia in spontaneously breathing rats. , 2003, American journal of veterinary research.

[37]  J. O'neil,et al.  Pulmonary function testing in small laboratory mammals. , 1984, Environmental health perspectives.

[38]  J. H. Comroe,et al.  A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease. , 1956, The Journal of clinical investigation.

[39]  Z. Hantos,et al.  Assessment of respiratory mechanics in small animals: the simpler the better? , 2002, Journal of applied physiology.

[40]  G. Holstege,et al.  The Nucleus Retroambiguus Control of Respiration , 2009, The Journal of Neuroscience.

[41]  M. Burt,et al.  A simplified method for endotracheal intubation in the rat. , 1994, Journal of applied physiology.

[42]  S. Gandevia,et al.  Postural activity of the diaphragm is reduced in humans when respiratory demand increases , 2001, The Journal of physiology.

[43]  B. Westerink,et al.  A novel and simple method for endotracheal intubation of mice , 2007, Laboratory animals.

[44]  Y. Shimada,et al.  Evaluation of a hot-wire respiratory flowmeter for clinical applicability. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[45]  C. Coggins,et al.  Measurement of respiratory patterns in rodents using whole-body plethysmography and a pneumotachograph , 1981, Laboratory animals.

[46]  Y. Colman,et al.  Microstream capnograpy technology: a new approach to an old problem. , 1999, Journal of clinical monitoring and computing.

[47]  M. Heinricher,et al.  A simple device for humidification of inspired gases during volatile anesthesia in rats. , 2005, Contemporary topics in laboratory animal science.

[48]  P M Gustafsson,et al.  Evaluation of various models for respiratory inductance plethysmography calibration. , 1993, Journal of applied physiology.

[49]  H. Moseley,et al.  Capnometry and anaesthesia , 1992, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[50]  Wayne Mitzner,et al.  Invasive and noninvasive methods for studying pulmonary function in mice , 2007, Respiratory research.

[51]  C. Subban,et al.  Chronic in utero buprenorphine exposure causes prolonged respiratory effects in the guinea pig neonate. , 2010, Neurotoxicology and teratology.