The Effect of Aminophylline on Diaphragm Blood Flow in the Piglet

Mayock, Dennis E.; Twiggs, Gary A; Standaert, T. A.; Watchko, Jon F.; Woodrum, D. E.

doi:10.1203/00006450-198909000-00005

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Gayan‐Ramirez

Buts²,

Decramer³

1994

Eur Respir J

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T Tw wi it tc ch h p po ot te en nt ti ia at ti in ng g e ef ff fe ec ct ts s o of f t th he eo op ph hy yl ll li in ne e o on n r ra at t d di ia ap ph hr ra ag gm m a ar re e e en nh ha an nc ce ed d b by y f fo or re es sh ho or rt te en ni in ng g G. Gayan-Ramirez, N. Buts, M. Decramer Twitch potentiating effects of theophylline on rat diaphragm are enhanced by foreshortening. G. Gayan-Ramirez, N. Buts, M. Decramer. ERS Journals Ltd 1994 ABSTRACT: In patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, acute hyperinflation is likely to induce foreshortening of inspiratory muscles. Since no data are available on the effects of inotropic agents at lengths below the optimal length (L o ), we compared the effects of theophylline on forty rat diaphragm bundles placed at L o and at 70% L o .Twitches and tetanic stimulations were recorded before and after addition of theophylline, in concentrations of 20, 100, 200 or 400 mg·l -1 .Compared with values obtained before theophylline, twitch tension (P t ) and maximal tetanic tension (P o ) of the bundles placed at L o slightly decreased at 20 and 100 mg·l -1 whereas a clear increase in P t was obtained at 400 mg·l -1 (15±21% (mean±SD)). In contrast, P t of the bundles placed at 70% L o increased with all theophylline concentrations, and vastly more than at L o (e.g. at 400 mg·l -1 : 74±34%, p<0.05); whereas P o slightly decreased, except at 400 mg·l -1 . Moreover, the difference between the effects at L o and at 70% L o increased with increasing theophylline concentrations.We conclude that even at low, in vivo attainable serum levels, theophylline exerted greater positive inotropic effects on twitch tension (P t ) of rat diaphragm when foreshortened than when at optimal length.

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Section: Discussionmentioning

confidence: 99%

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

Gayan‐Ramirez

Buts²,

Decramer³

1994

Eur Respir J

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“…We have previously demonstrated that aminophylline does not change the pressure-generating capacity of the nonfatigued piglet diaphragm during spontaneous breathing (1 8), nor was there any effect on resting diaphragmatic blood flow (19). The present study was designed to examine the effect of methylxanthines on fatigued diaphragm for several reasons.…”

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confidence: 99%

Effect of Methylxanthines on Diaphragmatic Fatigue in the Piglet

1992

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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...

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