Effect of Methylxanthines on Diaphragmatic Fatigue in the Piglet

Abstract

ABSTRACT. Studies in adult animal and human subjects have suggested that the methylxanthine drugs can delay the onsGir attenuate the severity of diaphragmatic fatigue. We have investigated the effect of aminophylline and caffeine on the pressure-generating capacity of the fatigued diaphragm in 1-mo-old piglets. Measurements of ventilation, transdiaphragmatic pressure, blood gases and pH, diaphragmatic electromyogram, diaphragmatic pressurefrequency curve (PdiFC), diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 90 min of inspiratory resistive loaded breathing (IRL), and again 30 min after methylxanthine infusion while still on IRL. IRL resulted in a significant decrease in minute ventilation secondary to a fall in tidal volume. Spontaneously generated transdiaphragmatic pressure increased 7-fold from baseline. EMG activity increased to both segments of the diaphragm. Abdominal expiratory muscle activity was noted after the onset of IRL and was accompanied by a fall in end-expiratory lung volume. The PdiFC was significantly decreased from baseline after 90 min of IRL, demonstrating diaphragmatic fatigue. Aminophylline did not alter the PdiFC of the diaphragm. Diaphragmatic electromyogram and tidal volume increased. No change in diaphragmatic blood flow was demonstrable after infusion of aminophylline. Serum theophylline levels averaged 117 + 11 pmol/L (21 2 2 pg/mL). Caffeine administration did not alter the PdiFC or the diaphragmatic electromyogram during IRL. Blood flow to both segments of the diaphragm decreased after caffeine infusion. Serum caffeine levels averaged 86 f 30 pmol/L (16.6 + 5.9 pg/mL). We conclude that the methylxanthines, aminophylline and caffeine, do not reverse the loss of pressure generation by the diaphragm that occurs after 90 min of IRL in the anesthetized piglet. (Pediatr Res 32: 580-584, 1992 Supported by NIH Program Project Grant HL 39187. 5(1-7). Improved force output was documented for both fatigued (1, 3, 6, 7) and nonfatigued diaphragmatic muscle (1, 7). Some investigators have found little or no improvement in diaphragmatic contractility after methylxanthine therapy (8-12), whereas others have demonstrated that methylxanthines may, in fact, aggravate diaphragmatic fatigue (1 3, 14). Methylxanthines have recently been proposed as adjunctive therapy in weaning preterm infants from mechanical ventilation (1 5). Preliminary reports have suggested that methylxanthines may improve diaphragmatic pressure output during the neonatal period (16, 17). Lopes et al. (16) found that theophylline increased mouth occlusion pressure for a given diaphragmatic EMG level in preterm human infants. However, only three infants were completely studied, and this preliminary investigation has not been subsequently confirmed. More recently, McGilliard and Farrell (1 7) presented preliminary evidence that methylxanthines produced a dose-dependent increase in twitch tension in isolated neonatal rat diaphragm. However, the concentration of drug used was high, and it i...

The Effect of Theophylline on the Prevention of Mechanical Ventilation-Induced Diaphragm Atrophy in Rats

“…danialou et al [22] showed that theophylline causes a significant vasodilatation on diaphragm arterioles. On the contrary, the study by Mayock et al [26] on animals reported that there was no change in diaphragmatic blood flow after aminophylline infusion. However, methylxantine-derived drugs are reported to weaken the intensity of diaphragmatic weakness or can delay the start.…”

A suplementação de cafeína por 4 dias, seguida de ingestão aguda, não impactou na potência de triatletas após realizarem exercício de intensidade submáxima

“…It is known that elevated VE may increase the partial pressure of alveolar/muscular oxygen and consequently induce improvements in performance in endurance [11]. In certain investigations, they failed to observe these findings, because the acute use of caffeine during the performance of a submaximal exercise at steady state (i.e., above 75% the VO2max) revealed increases in diaphragm muscle fatigue [29,11]. Therefore, it does not seem prudent that fatigue of the diaphragm muscle could be associated to the findings observed in our study, because the fatigue installed in this muscle can promote significant reductions in the VE [11], and this was not observed (Figure 2 D, P>0.05).…”

Twitch potentiating effects of theophylline on rat diaphragm are enhanced by foreshortening

“…Thus, it is possible that by inducing systemic vasodilation, theophylline may also increase diaphragmatic blood flow, and thereby improve diaphragmatic force. However, several studies have demonstrated that diaphragmatic blood flow failed to increase after aminophylline [35][36][37], even when animals were breathing against an inspiratory resistive load [36,37], thus, showing that aminophylline has no direct effect on diaphragmatic arterioles. Moreover, we recently compared in vivo the effects of aminophylline on canine diaphragm stimulated at functional residual capacity (FRC) and near total lung capacity (TLC) (producing a diaphragm shortening similar to that in the present in vitro study), and we observed results similar to those obtained in vitro [38].…”