CHANGES IN RESPIRATORY MECHANICS MEASURED BY IOS DURING THE FIRST DAY OF LIFE IN CALVES CH. UYSTEPRUYST, P. REINHOLD *, J. COGHE, F. BUREAU, T. DORTS AND P. LEKEUX. Laboratory for Functional Investigation, Department of Large Animal Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Belgium, *Federal Institute for Health Protection of Consumers and Veterinary Medicine, Jena Branch, Germany Introduction To reduce perinatal calf mortality (6-8%) (Randall, 1978; Mee, 1999), it is necessary to understand the rapid changes that the cardiopulmonary system undergoes during successful transition to extrauterine life (Adams et al 1991, 1992). Indeed, around 60 % of these deaths occur during the first 24 hours post parturition (Vestweber 1997). Knowledge of the physiological mechanisms underlying the normal neonatal respiration is a prerequisite for evaluation of the failing mechanisms and for all rational therapeutic measures. Arterial blood gas analysis and pulmonary function tests are considered to be the reference methods to evaluate pulmonary function efficiency in cattle (Lekeux et al 1984, Gustin et al 1988). The impulse oscillometry system (IOS) is a newly developed forced oscillation technique which has been used for non-invasive respiratory function testing in children (Bisgaard and Klug 1995, Klug and Bisgaard 1998), in horses (van Erck et al 1997), in pigs (Klein and Reinhold 1997) and in calves (Strie et al 1997, Reinhold et al 1996, 1998a, 1998b). In the present study, arterial blood gas analyses and IOS were used to assess the physiological respiratory modifications occurring during the first 24 hours of life in healthy newborn calves. Material & Methods Calves Forty clinically healthy newborn calves (8 Holstein-Friesian weighing 41 (6.2) kg, 25 Blue Belgian weighing 51.0 (7.0) kg and 7 crossbred weighing 47.0 (4.4) kg) were investigated during their first 24 hours of life. Each calf was investigated 1, 2, 3, 6, 12, 18 and 24 hours after birth. Arterial blood gas analyses Arterial blood samples were withdrawn anaerobically from the Art. subclavia with a 2 ml heparinised syringe and were analysed within 2 minutes by a blood gas analyser (AVL 995, VEL, Leuven, Belgium) for blood gas tensions as well as for acid-base balance. Impulse oscillometry measurements In this study, the complex respiratory impedance (Zrs) was measured by use of an IOS device (MasterScreen IOS, E. Jaeger GmbH, Würzburg, Germany). The IOS measured the complex Zrs which is derived from the ratio of spectral pressure and flow variations (Zrs = P/V’) after fast fourier transformation (FFT) of pressure and flow from the time domain. The IOS calculated the following parameters: resistance at 5, 10, 15, 20, 25, 35 Hz (R 5Hz,…R35Hz), and reactance at 5, 10, 15, 20, 25, 35 Hz (X5Hz,…X35Hz). Results Changes in arterial blood ANOVA revealed a highly significant effect of the age of the calf (p < 0.001) on arterial blood parameters. From 1 to 24 hours old, PaO 2, SatO2, pHa and BEa increased significantly (p < 0.01) while PaCO2 and A-aDO2 decreased significantly (p < 0.01). Changes in respiratory mechanics ANOVA showed that the respiratory mechanical parameters measured with the IOS were significantly influenced by the age of the calf (p < 0.01). This analysis also demonstrated that the body position of the calf influences significantly R5Hz (p < 0.001), R10Hz (p < 0.05) and X5Hz,…X35Hz (p < 0.001). Since there was no significant change within the first 3 hours of life (1, 2, 3 h) and between 18 and 24 hours, R and X values of these time periods were pooled and directly compared in Fig. 1a for the lying position and in Fig. 1b for the standing position. Fig. 1a and Fig. 1b show that R was negatively dependent on frequency (R decreased when frequency increased). R was more negative dependent on the frequency in the lying position compared to the standing position. Furthermore, a negative dependency of R on frequency observed at 1-3 hours was still present at 18-24 hours of age but was slighter. Between the two time periods (1-3 hours and 18-24 hours), R5Hz,…R35Hz decreased significantly (p < 0.05) and X5Hz,…X35Hz increased significantly (p < 0.05) as shown in Fig. 1a and Fig. 1b. A Dunnett t test showed that the absolute changes in R and X with time (between 1 and 24 hours old) were significantly higher at 5 Hz than at 15, 20, 25 and 35 Hz for R (p < 0.05) and significantly higher at 5 Hz than at 20, 25 and 35 Hz for X (p < 0.05). Intra-subject variability of the respiratory impedance Between 1-3 hours and 18-24 hours, the intra-subject variability in R (represented by the DiffR values, i.e. the difference between the maximal and the minimal values within 3 consecutive IOS-measurements) did not change significantly. In contrast, the intra-subject variability in X (represented by the DiffX values) decreased significantly for 10 Hz, 15 Hz, 20 Hz and 25 Hz (Fig 2). Furthermore, the lower the frequency the higher the absolute value of DiffX (Fig 2). 1.0 1.0 a b 1-3 hours 18-24 hours 0.8 0.6 R 0.4 * * * * * * * * * * 0.2 * * 0.4 KPa.l-1.s KPa.l-1.s 0.6 0.0 1-3 hours 18-24 hours 0.8 R * * * * * * * * * * * 0.2 0.0 * X X -0.2 -0.2 -0.4 -0.4 5 10 15 Frequency 20 (Hz) 25 35 5 10 15 Frequency 20 (Hz) 25 35 1-3 18 - 24 0.25 * + 0.20 0.15 hours hours p < 0.01 p < 0.05 * * 0.10 * + 0.05 0.00 DiffX 5Hz DiffX 10Hz DiffX 15Hz DiffX 20Hz DiffX 25Hz DiffX 35Hz KPa.l-1.s FIG. 1a and 1b : Resistance at 5,…35 Hz (R5Hz,…R35Hz) and reactance at 5,…35 Hz (X5Hz,…X35Hz) changes with time in calves in the lying (a) and in the standing (b) positions (mean (SD)). FIG. 2 : Changes in the intra-subject variability in reactance at 5,…35 Hz (DiffX(5Hz,….35Hz) ) between 1-3 hours and 18-24 hours in 40 newborn calves (mean (SD)). Discussion This study shows that, during the first 24 hours of life of healthy newborn calves, gas exchange improves and the mixed respiratory-metabolic acidosis present at birth is corrected as demonstrated by significant changes in arterial blood gases and acid-base balance. These changes were accompanied by concomitant changes in pulmonary mechanics. The first 6 hours of life represent the most critical adaptive period, major changes occurring during this period. From birth to 1 day old, pulmonary function tests measured by the IOS revealed significant decrease in R and increase in X with time, reflecting the clearance of both upper and lower airways, the increase in lung volume and the improvement of the lung tissue elasticity and/or the improved distribution of the ventilation occurring during this adaptive period. The IOS spectral analysis (from 5 to 35 Hz) offered refined information concerning the location of mechanical changes within the respiratory system: indeed, greatest changes in R and X with time were observed at lower frequencies, suggesting that major mechanical changes occur within peripheral airways where foetal lung fluid is removed. The negative frequency dependence of R may be related to a normal spectral behaviour of R for a small size lung system with an additional negative dependency due to a peripheral airway obstruction. This negative dependency still present at 1 day old suggests that the removal of foetal lung fluid takes longer than 24 hours. The significant decrease with time in the intra-subject variability of X-values within the range 10 - 25 Hz suggests a decreased variability of the respiratory system during the first day of life. Since no significant change in DiffR was detected, it seems to be related more to the central and peripheral airway system and/or the elasticity of the lung tissue than to the upper or larger airways. This study also demonstrates the effect of body posture on respiratory mechanics and particularly on mechanical properties of the distal respiratory system and/or chest wall. At 1 day old, both mechanical parameters and arterial blood gases remain lower (higher R values, lower X values, relative hypoxaemia due to right-to-left shunting mainly through areas of the lung with a low ventilationperfusion ratio,…) than predicted values of older healthy calves of the same body weight, meaning that the pulmonary adaptation to extrauterine life takes longer than 24 hours. The present results provide data concerning a successful transition to extrauterine life in calves. They might be valuable when investigation of calves presenting an adaptation failure or delay will be required. References Adams R, Holland MD, Aldridge B, et al. Arterial blood sample collection from the newborn calf. Vet Res Com 1991;15: 387-394. Adams R, Garry F B, Aldridge B M, et al. Hematologic values in newborn beef calves. Am J of Vet Res 1992;53: 944-950. Bisgaard H, Klug B. Lung function measurement in awake young children. Eur Respir J 1995;8: 2067-2075. Gustin P, De Groote A, Dhem A R, et al. A comparison of pO2, pCO2, pH and bicarbonate in blood from the carotid and coccygeal arteries of calves. Vet Res Com 1988;12: 343-346. Klein C, Reinhold P. Analysis of respiratory mechanics in pigs using impulse oscillometry. In Proceedings : 15th Comparative Respiratory Society Meeting, Liege, Belgium, 1997;P/2.6. Klug B, Bisgaard H. Specific airway resistance, interrupter resistance, and respiratory impedance in healthy children aged 2-7 years. Pediatr Pulmonol 1998;25: 322-331. Lekeux P, Hajer R, Breukink HJ. Effect of somatic growth on pulmonary function values in healthy Friesian cattle. Am J of Vet Res 1984;45: 20032007. Mee JF. Stillbirths-What can you do ? Cattle Practice 1999;7(3): 277-281. Randall GCB. Perinatal mortality : some problems of adaptation at birth. Adv Vet Sci Comp Med 1978;22: 53-81. Reinhold P, MacLeod D , Lekeux P. Comparative evaluation of impulse oscillometry and a monofrequency forced oscillation technique in clinically healthy calves undergoing bronchochallenges. Res Vet Sci 1996;61: 206213. Reinhold P, Smith HJ, Langenberg A, et al. Measurement of respiratory impedance in healthy calves using the impulse oscillation technique Physiological and methodological aspects. Vet J 1998;155: 27-38. Reinhold P, Smith H J, Close R, et al. Validation of impulse oscillometry in Friesian and Blue Belgian calves with respect to changes in extrathoracic upper airway resistance. Res Vet Sci 1998;65: 93-102. Strie R, Doll K, Pöttmann B, et al. The impact of several factors on the lung function test results of calves and young bulls employing multi-frequency impulse oscillometry (IOS). In Proceedings : 15th Comparative Respiratory Society Meeting, Liege, Belgium, 1997;P/2.11. van Erck E, Art T, Lekeux P. Evaluation of the IOS as a non-invasive method for pulmonary function testing in horses. In Proceedings : 1997 BEVA Congress, Harrogate, Great Britain, 1997;141-142. Vestweber JG. Respiratory problems of newborn calves. Vet Clin North Am Food Anim Pract 1997;13: 411-424.