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AUTOMATED IN VIVO MEASUREMENT OF
QUASI-STATIC LUNG COMPLIANCE IN THE RAT
Acknowledgment: Funded, in part, by State of Connecticut Apollos Kinsley Yankee Ingenuity Initiative Grant 91k011
THE LABORATORY RAT IS WIDELY USED IN EXPERIMENTAL LABORATORY PROCEDURES. In pulmonary medicine,rats are utilized for determining the efficacy of ventilation and pharmacological techniques. The duration of these experimental procedures ranges from minutes to hours to days. During these experiments, it is often desirable to monitor the effect of the protocol on pulmonary function. Quasi-static in-vivo lung compliance is a routinely performed procedure which is non-invasive and highly representative of lung function. historically, these compliance tests have been conducted manually. This requires a specially trained technician to blow info tubing which is connected to a tracheostomy catheter, a delicate procedure which requires a high degree of technical mastery. Therefore a trained individual must be present any time the test is run, often making the test inconvenient and variable.
To facilitate the use of this procedure, we have developed equipment which automates quasi-static in-vivo lung compliance measurements. When utilized during either conventional or jet ventilation, this system interrupts treatment to measure compliance and immediately re-initiates it upon completion of the test. It accepts a single pulse signal to initiate the testing sequence and, through a logic network, electronically controls the opening and closing sequence of the valves. This sequence includes sealing off the humidified air flow channel, inflating the animal's lungs, and then allowing them to deflate over a 10-12 second period. The animal is enclosed in a plethysmograph which is airtight and has a heat sink of copper mesh. Pressure corresponding to changes in lung volume, per the ideal gas law. Airway opening and esophageal pressure transducers are used to determine the transpulmonary pressure is then input into an x-y recorder for plotting of the pressure-volume curve. The compliance measurement can then be determined from this hysteresis-shaped curve.
This automated system makes lung compliance measurement more accurate and convenient for researchers studying models of lung injury using the laboratory rat.
INTRODUCTIONRats are widely used in experimental laboratory procedures worldwide. Their utility arise from the small genetic variation narrowing the range of physiological responses to any given low cost make them ideal for many experiments. For example, in pulmonary medicine, they are utilized for analysis of ventilation techniques (e.g. Cilley et al. 1993), and pharmacological treatment for lung disorders (Thrall et al. 1981; Thrall et al. 1987).
Lung compliance measurement is a direct mechanical evaluation of the health of the lung. Static lung compliance, (inflation compliance), the average compliance over the entire inspiration phase, is the measurement most often used by clinicians. Quasi-static compliance measures compliance at discrete points of time during expiration, and is therefore more representative of the instantaneous compliance magnitude. further, static lung compliance has been shown to be affected by other factors not related to lung function, such as the ventilator settings peak inspiratory pressure (PIP) AND POSITIVE end physicians feel that quasi-static compliance is a more valuable measure of lung mechanics than static lung compliance.
Presently, quasi-static lung compliance measurements of laboratory animals require a trained technician to perform the procedure, making them inconvenient and variable. The purpose of this project was to develop equipment which automates quasi-static, in vivo, lung compliance measurements. Designed to be used during either conventional or ft ventilation, the system interrupts ventilation to measure lung volume and transpulmonary pressure and re-initiates it upon completion of the test. These capabilities make the measurement of quasi-static lung compliance more reproducible and convenient for researchers studying models of lung injury using the laboratory rat.
COMPLIANCE MEASUREMENT TECHNIQUESLung compliance measurement is a direct mechanical evaluation of the health of the lung. Compliance (inverse elasticity) is traditionally defined as the change in lung volume (dV) associated with a change in pressure
For clinical studies, the differentials dV and dP are approximated by the finite difference deltaV and deltaP. Lung compliance, CL, is then given by the charge in lung volume, deltaVL, divided by the change in transpulmonary pressure, deltaPtrans:
2. CL=deltaVL / deltaPtrans
Transpulmonary pressure is taken as lung minus esophageal pressures. Static lung compliance is the total change in volume of the lung divided by the total change in transpulmonary pressure from beginning of inspiration to its end (Cotes 1993). This may be obtained from
3. CStatic=Vt / (PIP-PEEP)
where Vt is tidal volume
PIP is peak inspiratory pressure
PEEP is positive end-expiratory pressure.
Both Equations 2 and 3 are approximations to Eqn. 1.In practice, the varies ventilator PIP to vary the patient's PaO2 level. When PaO2 rises too high, PIP is lowered; when it is depressed, pressure is increased (Cote 1993). Consequently, static lung compliance measured via Eqn. 3 will vary greatly with the ventilation changes. Snider and colleagues (1977) showed that in the laboratory and average compliance (or chord compliance) measured between 15 and 25 cm H2 O transpulmonary pressure was not as sensitive to changes in lung condition than was quasi-static lung compliance.
Quasi-static lung compliance approximates Eqn. 1 using Eqn. 2 for finite differential changes in transpulmonary pressure. In practice, clinicians observing lung compliance take the steepest slope of the expiratory lung volume-pressure curve to be most indicative of the lung's health (Koo et al. 1976). This maximum slope is the quasi-static lung compliance measurement we adopt in this study.
In-vivo lung compliance tests of animals are currently conducted manually. The rat is placed in an air-tight plethysmograph. A small, flexible, water-filled tube is inserted into the esophagus, with the open end placed just above the diaphragm. Another tube is connected to a tracheostomy catheter. To start the test, a trained technician blows into the latter tube to inflate the lungs to 25 cm H2O pressure over a complete inflation/deflation cycle. Obtaining smooth variation in pressure and volume requires a high degree of technical mastery, making the test difficult to reproduce and inconvenient. This project automates the above procedure while permitting ventilation protocols to be followed between measurements.
For SYSTEM DESIGN,
RESULTS AND DISCUSSION,
AND LITERATURE CITED, click here
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