PROSTAGLANDINSLEUKOTRIENES ANDESSENTIALFATTYACIDS Prowglandms Leukotnenes and Euential Fatty Aads 0 Lonpman Group UK Lid 1992

c19931 47. 225-230

Inspiratory Timing Regulation of PGF2, in Newborn Pigs M.G. Clement,

M. Albertini,

lstituto di Fisiologia requests to MGC)

M. Dimori and G. Aguggini

Vererinaria e Biochimica,

Universitci di Milano. Via Celoria 10. 20133 Miiano, itafia (Reprint

ABSTRACT. In intact and vagotomized anesthetized, spontaneously breathing piglets, we investigated the regulation of inspiratory timing evoked by i.v. administration of prostaglandin (PC) F,,. The inspiratory time was evaluated from the flow trace as an index of mechanical inspiratory time (Ti) and from costal and crural diaphragmatic EMG (TIE& as an index of neural inspiratory time. Our results under control conditions showed that Ti,,, was shorter than Ti. Vagotomy abolished the difference, inducing a change in the power spectrum without modifying the centroid frequency (CD. PGF,, lenghthened T&o, causing a postinspiratory diaphragmatic discharge to appear, while mechanical inspiratory time decreased significantly. Postvagotomy iv. administration of PGFra did not cause any significant changes in inspiratory time and did not evoke the postinspiratory discharge. The i-v. administration of PGFza before and after vagotomy did not change the centroid frequency in spite of recruitment of new motor units synchronized with those that are active under control conditions.

11). Earlier studies have also suggested that PGF?,, acting as an intracellular mediator, may also modify the activity of the respiratory centers (12). It should not be forgotten that PGF?, is a bronchoconstrictive agent and that the increase in the bronchomotor tone might alter the phasic vagal input arising from the stretch receptors. These receptors are responsible for the vagus-dependent volume-time mechanism that regulates the bulbo-pontine rhythm (13-17). Because this off-switch vagal mechanism regulates not only the flow-volume, but also the duration of inspiration time, we wished to see whether the neonatal respiratory responses to PGF,, are vagus-dependent. Since Kosh (18, 19) has suggested that the electromyographic discharge of the diaphragm is an index of nerve control of respiratory cycle timing, we have evaluated the duration of the inspiration time from the flow tracing (Ti) and from the electromyographic tracing (T&o). The Tie,, from the costal and crural portions of the diaphragm were both evaluated, to obtain an index of the regulation of inspiration time evoked by PGF?,.

INTRODUCTION Immediately after birth the induction of respiratory activity and of rhythmic respiration are regulated by many factors. Some metabolites of arachidonic acid are important among these. They not only regulate respiratory movements, but also evoke the neonatal reflex which last consists of the appearance of apneic events during expiration and of modifications of diaphragmatic activity, with the appearance of diaphragmatic braking (l-3). This braking slows the expiratory flow to regulate the volume of the end of expiration and thus favors the formation of the functional residual capacity (44). Prostaglandin Fza (PGF?,) plays an important role in the regulation of this reflex. In the newborn pig it alters the rhythm of respiration, induces apneic spells and modifies the electromyographic activity of the diaphragm (7, 8). To be specific, it modifies the diaphragmatic EMG power spectrum, seen as a recruitment of the new motor units needed to ensure achievement of adequate muscle tension. In addition, according to Clement (8), PGF?, can modify diversely the activities of the costal and crural portions of the diaphragm, which have different segmental innervation and different mechanical activities during the movements of the thoracic cage (9-



The experiments were performed on a total of 7 newborn Large White piglets of either sex, weighing 2.05 f 0.12 (SEM) kg, all l-3 days of age. The animals were anesthetized with sodium thiopental

Date received 1 April 1992 Date accepted 14 May 1992 225




and Essential Fatty Acids

(1.5 mg/kg, i.v.. first injection; 5 mg/kg drop by drop continuous i.v. infusion). The animals rested supine on a heated operating table. Rectal temperature was monitored continuously and kept between 37-38 “C. After tracheostomy. a tracheal cannula was inserted into the lower portion of the extrathoracic trachea and connected to a Fleish pneumotachograph no. 0 to record respiratory airflow (9) and, by electronic integration, tidal volume (Vt). The left femoral artery was cannulated with a polyethylene catheter to monitor arterial blood pressure (BP). The left femoral vein was cannulated to administer anesthetic and PGF,,. After median laparotomy, two pairs of bipolar fish-hook electrodes (0.4 cm apart) were inserted on the anterior part of the costal and crural diaphragm. The electromyographic signals (EMG) were amplified by a Grass amplifier (RPS 107), band-pass filtered between 20 Hz and 2000 Hz. Raw EMG signals were also stored on an FM magnetic tape recorder (Racal 4 channels) and then played back through an anti-aliasing filter with low pass filter set at 1000 Hz (frequency devices, Model 902) and digitized at 2000 Hz by a 12-bit analogue-digital converter (Data Translation Inc Model 282 1). EMG signals throughout the entire inspiratory phase were processed with the Hanning window function and Fast Fourier Transformation by a personal computer (Olivetti M380). to obtain the power spectrum. The power spectra were quantified in terms of the centroid frequency (Cf). Mechanical ventilation (Vt of lo-12 ml/kg and frequency of 30/min) was maintained throughout the surgical procedure. After insertion of electrodes on the costal and crural parts of the diaphragm, the abdominal wall was sutured and the animals were disconnected from the ventilator and allowed to breath room air through the pneumotachograph. Records of V, Vt and BP were made on Net San-ei Instruments polygraph (Mod. 8K40).


between two sets of data was assessed by the two-tailed t-test for paired and unpaired data. A significant difference was defined as ~~0.05.

RESULTS Our results show that iv. administered PGF,, caused expiratory apnea, prolonging expiration and causing a postinspiration diaphragmatic discharge. The values in Table 1 are for control conditions and after PGF,, administration to both non-vagotomized and bilaterally vagotomized animals. The data for the prevagotomized animals are the peak effects, the maximal prolongations of the expiratory time (Te). The peak appeared within 1 min after the end of administration in 3 of the 7 piglets and in the other 4 piglets within about 10 min. Because PGF,, did not cause any significant changes in expiratory time after vagotomy, the values are referred to same prevagotomy times. Before and after vagotomy. i.v. administration of PGF,, did not change BP (data not reported). Before vagotomy, PGF,, caused a significant decrease in respiratory frequency, essentially due to prolongation of the Te, and significant increases in Vt and inspiratory flow (Vtni) without changing the pulmonary ventilation (Vm). Vagotomy raised Vt and decreased Fr. without changing Vm or Vt/ Ti. PGF?, administered after vagotomy did not change the breathing pattern. The data for the mechanical expiratory and inspiratory times and neural times evaluated from the costal (Ti EMG,coJ and crural (Ti,,o,_) diaphragmatic EMG are reported in Table 2. For these, too, the values are for prevagotomy and postvagotomy under control conditions and after i.v. administration of PGF,,. PGF,,, significantly lengthened Te from 1.35 f 0.22 (SEM) s to 2.50 + 0.37 (SEM) s (p

Inspiratory timing regulation of PGF2 alpha in newborn pigs.

In intact and vagotomized anesthetized, spontaneously breathing piglets, we investigated the regulation of inspiratory timing evoked by i.v. administr...
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