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Inactivity-induced phrenic motor facilitation is associated with decreased phrenic burst-to-burst variability. Corie Borchert Dept. of Comparative Biosciences. Diaphragm = Muscle. Cervical region of spinal cord. Lungs inflate. Lungs deflate. Respiratory problems. Spinal cord injury.
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Inactivity-induced phrenic motor facilitation is associated with decreased phrenic burst-to-burst variability Corie Borchert Dept. of Comparative Biosciences
Diaphragm = Muscle Cervical region of spinal cord
Lungs inflate Lungs deflate
Respiratory problems Spinal cord injury Sleep apnea
Respiratory Plasticity - Ability to adjust to disruption of respiration - Modify existing proteins - Initiate transcription and translation of new proteins ***Enhance synaptic transmission Axon terminal Synapse
Model to study inactivity-induced neural plasticity (iPMF) Intrathecal catheter Adult male rats that are: Phrenic motor nucleus C3-C5 Urethane anesthetized Ventilated Paralyzed Vagotomized Intrathecal catheter Spinal cord Phrenic nerve Diaphragm Measure “breathing” by monitoring phrenic burst discharge This preparation allows us to separate the neural control of breathing from the process of ventilation ? Source: Kristi Strey, Baker-Herman Lab
Inactivity-induced phrenic motor facilitation (iPMF) Neural Apnea Baseline 60 minutes Source: Baker-Herman TL (2009). Phrenic motor facilitation following phrenic inactivity requires spinal atypical PKC activity.
Genetic differences? A. B. C. Source: Fuller DD, Baker TL, Behan M, Mitchell GS (2001). Expression of hypoglossal long-term facilitation differs between substrains of Sprague-Dawley. Physiol Genomics. 4: 175-181. Strey KA and Baker-Herman TL (2011). Local reductions in synaptic inputs to the phrenic motor pool elicits inactivity-induced phrenic motor facilitation (iPMF). 5th SFN Satellite Symposium on Motor Systems abstract. Sustained iPMF Harlan Sprague-Dawley Transient iPMF Charles River Sprague-Dawley Sustained iPMF Charles River Sprague-Dawley + APV Respiratory neural apnea 5 min 15 min 30min 60 min
Heart Beat Variability Source: M. Frenneaux, Autonomic changes in patients with heart failure and in post-myocardial infarction patients, Heart, 2004
Respiratory Variability and Ventilator Weaning Weaning success Weaning failure Source: MY Bien et al.Breathing pattern variability: a weaning predictor in post-operative patients recovering from systemic inflammatory response syndrome. Intensive Med Care 2004
? ? ? ? Is there a change in burst-to-burst variability following neural apnea? ? ? ? ? ?
Hypothesis Inactivity-induced phrenic motor facilitation (iPMF) is associated with a change in phrenic burst-to-burst variability
Methods • Electrophysiology data from Harlan and Charles River rats • 400 breaths from baseline, and both 5 and 60 minutes post neural apnea • Inspiratory time (Ti, ms) • Expiratory time (Te, ms) • Height (mV) • Peak Area (mV) Height Te Peak Area 3) Analyzed using “R” software and Poincare plots 4) Performed two-way repeated measures ANOVA tests for the standard deviations (SD 1 and SD 2) Ti
Time Control Baseline 60 min. 5 min. Ti
60 min. 5 min. Baseline Harlan Neural Apnea CR Neural Apnea CR Neural Apnea + APV
Results * p < 0.05
Results * p < 0.05
Conclusions • Sustained iPMF in Harlan and CR APV rats • Decreased variability, 5 and 60 min. • Transient iPMF in CR rats • *iPMF is associated with decreased burst-to-burst variability • Impact of changes is unknown • Mode of protection? • Implications of respiratory plasticity • Future uses and studies
QUESTIONS? *Funded by the UW-Madison Regent Scholars Fund and NIH Grant HL 105511