Repeated intravenous doxapram induces phrenic motor facilitation
M S Sandhu1, K Z Lee, E J Gonzalez-Rothi
1Department of Physical Therapy, College of Public Health and Health Professions, McKnight Brain Institute, University of Florida, P.O. Box 100154, 100 S. Newell Drive, Gainesville, FL 32610, USA.
Experimental Neurology
|September 10, 2013
Summary
Intermittent low doses of doxpram, a respiratory stimulant, can induce long-lasting improvements in phrenic motor output, suggesting potential for respiratory neuroplasticity and rehabilitation.
Area of Science:
- Neuroscience
- Respiratory Physiology
Background:
- Doxapram is a known respiratory stimulant used to treat hypoventilation.
- The potential for doxapram to induce long-term changes in respiratory control (neuroplasticity) is not well understood.
Purpose of the Study:
- To investigate if intermittent, low-dose doxapram administration can induce lasting increases in phrenic motor output.
- To explore the potential of doxapram for triggering respiratory neuroplasticity.
Main Methods:
- Anesthetized, vagotomized, and mechanically-ventilated rats received intravenous doxapram (single 2 or 6mg/kg bolus, or three 2mg/kg injections at 5-min intervals) or saline vehicle.
- Phrenic motor output was measured.
- Carotid sinus nerves were sectioned to assess the role of chemoreceptors.
Main Results:
- Repeated low-dose doxapram injections (3 x 2mg/kg) significantly increased phrenic burst amplitude 60 minutes post-injection (168±24% of baseline).
- Single doxapram doses (2 or 6mg/kg) did not produce lasting increases in phrenic output.
- The acute response to low-dose doxapram was significantly reduced after carotid sinus nerve section, indicating a role for carotid chemoreceptors.
Conclusions:
- Intermittent administration of doxapram can induce phrenic neuroplasticity, characterized by long-lasting facilitation of phrenic motor output.
- This intermittent dosing strategy may hold promise for respiratory rehabilitation, particularly following neurological injuries.
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