Table 1.
Clinical and experimental measures of respiratory function
| Blood gases | |
| Use: clinical and some experimental | Considerations |
| - Measure of oxygen and carbon dioxide partial pressures, and pH from blood sample | - Repeated measures in animals can be limited by the small blood volume of most experimental animals |
| - As such, it is the most accurate reflection of respiratory efficiency (adequacy of gas exchange) | - In many cases, sampling from awake animals is difficult without causing stress (directly affecting respiration) |
| - Blood samples have potential for used in assessing biomarkers of injury, plasticity and repair | - Difficult to relate to underlying anatomy and might be influenced by circulatory dysfunction |
| Oximetry | |
| Use: experimental and clinical | Considerations |
| - Measure of hemoglobin saturation in arterial blood | - Oxygen saturation might not be compromised in common experimental SCI models, or might only be reduced following severe injury |
| - Noninvasive | - Cannot determine concentration of carbon dioxide or sodium bicarbonate, or pH |
| - Might not directly correlate with ventilation | |
| Spirometry | |
| Use: clinical | Considerations |
| - Uses a pneumotachograph to measure airflow to and from lungs | - Might reflect compensatory mechanisms by unaffected circuits (e.g. increased intercostal activity might offset diaphragm dysfunction, so parameters of ventilation are relatively unaffected). Thus, this method does not necessarily provide information about mechanisms of recovery. However, as respiration can be measured in absolute units, we can determine with some certainty whether the overall output of the respiratory system is altered by injury or a particular intervention. |
| - Routinely used clinically as a pulmonary function test to determine multiple parameters, including forced vital capacity (FVC), forced expiratory volume per second (FEV1.0), inspiratory capacity (IC) and peak expiratory flow (PEF) | - Requires voluntary control of respiration and therefore cooperation and motivation of the subject |
| - Noninvasive | |
| - The ‘sniff’ test can be used as an additional measure for assessment of diaphragm function under increased drive | |
| Plethysmography | |
| Use: experimental and clinical | Considerations |
| - Measure of ventilation (gross measure of respiratory behavior) in terms of breathing frequency (f), tidal volume (VT) and minute ventilation (VE) | - Can reflect compensatory mechanisms by unaffected circuits as described for spirometry |
| - Noninvasive | - Measure is minute ventilation and not alveolar ventilation. Thus, changes in pulmonary dead space could lead to misleading conclusions. |
| - Clinically, can determine functional residual capacity more accurately than spirometry | - Common interferences to ventilation need to be carefully controlled |
| Imaging techniques (including chest X-ray, CT, ultrasound, fluoroscopy); see Ref. [89] for discussion | |
| Use: experimental and in some clinical circumstances | Considerations |
| - Visual representation of dysfunction (chest X-ray and CT) | - Usually only suggestive of dysfunction and requires confirmation with additional outcome measures |
| - Ultrasonography assesses real-time movement of diaphragm | |
| - Can be used to determine diaphragm thickness and change in muscle thickness during respiratory activity | |
| Electromyography (EMG) | |
| Use: experimental and in some clinical circumstances | Considerations |
| - Measure of muscle activity | - Muscle activity does not necessarily reflect a behavioral effect |
| - Chronic placement of electrodes can be used for repeated measures | - EMG recordings cannot sample the activity of the entire pool of active motor neurons. Because there are regional differences in the activation of respiratory muscles (e.g. costal versus crural diaphragm), recording from a single site might not accurately reflect diaphragm function. |
| - Can be noninvasive depending on muscle of interest | - Muscle atrophy could alter the signal |
| - Clinical recording is usually made noninvasively, placing electrodes on skin surface, decreasing accuracy of recording | |
| Nerve conduction recording using diaphragm CMAP (compound motor action potential) | |
| Use: Clinical | Considerations |
| - Noninvasive (electrode placed on skin) | - Electrode placement might not detect solely the nerve of interest |
| - Indirect measure of nerve function by assessing nerve integrity | - High-intensity stimulus is required, which might cause discomfort to subject |
| - Uses either electrical or magnetic stimulation | |
| Direct neurophysiological recording (exemplified by nerve recording described here) | |
| Use: Experimental (animal models) only | Considerations |
| - Direct measure of nerve function and relative motoneuron output | - Most neurophysiological recordings (e.g. from phrenic nerve) are terminal experiments |
| - The amplitude of the nerve burst reflects: | - Nerve activity does not necessarily reflect muscle activity |
| (i) the number of active motoneurons | - Nerve output does not necessarily reflect behavior, particularly because most studies are done under anaesthesia |
| (ii) the frequency of motoneuron discharge | - The amplitude of the nerve burst is also dependent on: |
| - Can compare between output from nerves on each side | (iii) electrode placement (proximity of the electrode to axons of active motoneurons) |
| - In the standard preparation (e.g. anesthetized, vagotomized, ventilated, etc.), many factors influencing breathing can be limited, and thus the output of a particular motor pool (e.g. phrenic) can be studied under carefully controlled conditions | (iv) the configuration of the recording system |
| - Can directly assess effect of treatment (serotonin agonists) and/or challenge (hypoxia) on motoneuron output | - Quantifying nerve output is problematic and there is no universally accepted method for quantifying the burst amplitude |
| - The peak height of the integrated phrenic inspiratory burst is highly correlated with peak airway pressure. Accordingly, many researchers have used this as an index of ‘respiratory neural drive.’ | - Comparing the burst amplitude between two nerves in the same rat (e.g. IL versus CL) or across rats can be problematic(e.g. even output in uninjured animals can differ between sides) |
| - Normalizing phrenic bursting to a maximum (e.g. asphyxic bursting) can remove physiologically meaningful differences between groups, as maximum bursting is reduced after SCI | |
Summary of some of the outcome measures used to assess respiratory function experimentally and/or clinically. The extent and detail of information provided by each test and necessary considerations are addressed. The most effective assessment of respiratory function is likely to come from use of multiple functional tests (e.g. nerve recording to assess function at the circuitry level, relative muscle activity assessed with EMG, plethysmography to measure overall breathing patterns and blood-gas analysis to determine respiratory efficiency).