Respiratory lung function - lung function unit

Assessment of spontaneous breathing pattern by whole body plethysmography

exploring	cleaning	sleeping

Whole Body Plethysmography - Measuring Principle

• During normal breathing, the box pressure signal due to tidal volume expansion is about 10 times larger than that resulting from alveolar gas decompression.
• Thus, there is only minimal information available regarding the resistance of the conducting airways, but
• tidal volume, respiratory rate, and timing can be reasonably estimated.

Gas conditioning: heating & humidification	Alveolar gas compression

Lung function parameters

The lung function unit allows to measure classical lung function parameters in anesthetized mice:

• Respiratory mechanics
  Lung volumes - FRC, IC, ERV, VC and TLC
  Lung compliance - static, dynamic
  Airway resistance
• Intrapulmonary gas transport
  Single breath maneuver - tesgas helium
  Dead space volume
  Slope of alveolar plateau
• Alveolar-capillary gas transfer
  Diffusing capacity for carbon dioxide (C18O)

Experimental setup: A schematic diagram of the experimental setup is shown in the Figure. The intubated mouse was connected to a custom made computer-controlled piston-type servo ventilator. In principle, this ventilator is a miniaturised version of the ventilator applied for lung function studies in dogs (Schulz et al. 1992a, 1992b) and exhibits corresponding functional characteristics. The ventilator allows for positive pressure ventilation at preselected tidal volumes and flow rates for the performance of reproducible breathing maneuvers for lung function testing. To adjust the test manoeuvres to the individual lung size, the system provides for independent respiratory settings of tidal volume, in- and expiratory flow as well as end-inspiratory and end-expiratory pauses. Furthermore, the operator has the choice to apply a released or a constant flow exhalation. For the instantaneous switch between different gas compositions for ventilation, e.g., for single-breath maneuvers, a set of four valves is connected to the piston. Care was taken to minimise the instrumental dead space volume (70 µl including tracheal cannula). A miniaturised pressure transducer (EPE-L21, Entran Sensoren GmbH, Ludwigshafen, Germany) located close to the end of the tracheal cannula allows for continuous measurement of airway opening pressure (P_ao). A second pressure transducer, located to the end of a thin-walled, water-filled tube which is connected to an esophageal cannula allows monitoring of the esophageal pressure (Poe). Concentrations of oxygen, carbon dioxide, labelled carbon monoxide (C¹⁸O), and helium are measured by a magnetic sector field mass spectrometer (modified M3, Varian MAT). Gas samples were taken close to the end of the tracheal tube through a 1-m heated inlet capillary with an inner diameter of 165 µm at a rate of 0.1 ml per second. The sampling rate as well as the delay and 5-95% response times of the mass spectrometer were controlled before and after each lung function measurement. The values for the delay times at different days ranged between 230-250 ms, those for the 5-95% response times between 35-40 ms.
The volume, pressure, and gas concentration signals were amplified and continuously recorded on a multichannel recorder (RS 3800, Gould). During lung function measurements, the signals of interest were also digitised and stored in a personal computer at a rate of 100-500 Hz. Before data analysis, the output signals of the mass spectrometer were corrected for the lag times and the volume signal of the ventilator for the suction rate of the mass spectrometer in order to obtain real time and volume data, respectively.

Penh does not assess respiratory mechanics in the classical sense. Rather it is an integrative parameter which is mainly influenced by changes in breathing pattern.

	Dose response curve

Schulz, H., Heilmann, P., Hillebrecht, A., Gebhart, J., Meyer, M., Piiper, J., Heyder, J. (1992): Convective and diffusive gas transport in canine intrapulmonary airways. J Appl Physiol 72, 1557-1562

Schulz, H., Eder, G., Heilmann, P., Ruprecht, L., Schumann, G., Takenaka, S., Heyder, J. (1992): Early responses of the canine respiratory tract following long-term exposure to a sulfur(IV) aerosol at low concentration. IV. Respiratory lung function. Inhalat Toxicol 4, 235-246

Reinhard, C., Eder, G., Fuchs, H., Ziesenis, A., Heyder, J., and Schulz, H. (2002): Inbred strain variation in lung function. Mamm Genome 13, 429-437

Schulz, H., Johner, C., Eder, G., Ziesenis, A., Reitmeier, P., Heyder, J., Balling, R. (2002): Respiratory mechanics in mice: strain and sex specific differences. Acta Physiol Scand 174, 367-375

Reinhard, C., Meyer, B., Fuchs, H., Stoeger, T., Eder, G., Ruschendorf, F., Heyder, J., Nurnberg, P., Hrabé de Angelis, M., Schulz, H. (2005): Genomewide linkage analysis identifies novel genetic loci for lung function in mice. Am J Respir Crit Care Med 171, 880-888