The effect of dipyridamole and theophylline on hypercapnic ventilatory responses: the role of adenosine

Griffiths, Timothy; Christie, Jane; Parsons, S. T.; Holgate, Stephen T.

doi:10.1183/09031936.97.10010156

Cited by 14 publications

(8 citation statements)

References 30 publications

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“…But as mentioned before it is known that exogenous adenosine stimulates ventilation by activating the carotid bodies. [8][9][10]30,32,34 Considering the results of this study it seems possible that endogenous adenosine influences the HVR and the ventilatory drive. This reaction could help the organism to fight against hypoxia as adenosine is released within tissues under hypoxic conditions, because of increased tissue-ATP-depletion as a consequence of reduced oxygen delivery.…”

Section: Discussionmentioning

confidence: 99%

Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

et al. 2004

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Adenosine, an endogenous nucleoside, is released by hypoxic tissue, causes vasodilation, and influences ventilation. Its effects are mediated by P1-purinoceptors. We examined to what extent the plasma adenosine concentration in the peripheral venous blood correlates with hypoxic ventilatory response (HVR) and ventilatory drive P0.1 to find out whether endogenously formed adenosine has an influence on the individual ventilatory drive under hypoxic conditions. While investigating the HVR of 14 healthy subjects, the ventilatory drive P0.1 was measured with the shutter of a spirometer. Determination of the ventilatory drive P0.1(RA) started under room air conditions (21% O (2)) and then inspiratory gas was changed to a hypoxic mixture of 10% O (2) in N (2) to determine P0.1(Hyp). At the time of the P0.1 measurements, two blood samples were taken to determine the adenosine concentrations. After removal of cellular components and proteins, samples were analyzed by high-pressure liquid chromatography (HPLC). Both adenosine concentrations in plasma under room air (r = 0.59, p < 0.05) and adenosine concentrations under hypoxia (r = 0.75, p < 0.01) correlated significantly with the ventilatory drive P0.1. In addition, plasma adenosine concentrations during hypoxic conditions showed a significant correlation with HVR on the 0.01 level (r = 0.71, p < 0.01). The results indicate a possible role of endogenous adenosine in the regulation of breathing in humans. We assume that endogenous adenosine influences the HVR and the ventilatory drive, probably by modulating the carotid body chemoreceptor response to hypoxia.

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Section: Discussionmentioning

confidence: 99%

Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

et al. 2004

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“…Indeed, it has been demonstrated that theophylline did not however, posthypoxic hyperoxic ventilation did not differ with affect either the intercept of the extrapolation of hypercapnic and without theophylline. In addition, we have shown that almiventilatory response to zero ventilation (an index of apneic trine, a drug that is associated with a comparable increase in threshold) or the slope of the hypercapnic ventilatory response resting ventilation did not affect the posthypoxic hyperoxic venti- (34). Notwithstanding the uncertainty of extrapolation the ventilation (19).…”

Section: Discussionmentioning

confidence: 99%

“…Notwithstanding the uncertainty of extrapolation the ventilation (19). These data indicate that changes in resting ventilalatory response to CO 2 to below eupnea and that normal subjects tion, at least in the range observed in our study, may not be an were studied (34), these findings indicate that theophylline does important determinant of ventilatory poststimulus potentiation. not alter the CO 2 -mediated ventilatory control, rendering the Previous studies have shown that patients with periodic breathlikelihood of a selective action of theophylline on apneic threshing such as those with sleep apnea syndrome or brain damage old rather unlikely.…”

Section: Discussionmentioning

confidence: 99%

Effects of Theophylline on Ventilatory Poststimulus Potentiation in Patients with Brain Damage

Mitrouska

Kondili

Prinianakis

et al. 2003

Am J Respir Crit Care Med

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Patients with brain damage, in contrast to normal subjects, exhibit a significant ventilatory undershoot when brief hypocapnic hypoxia is terminated abruptly by hyperoxia. This has been attributed to an impairment of activation of short-term potentiation, a brain stem mechanism promoting breathing stability. We hypothesized that in these patients theophylline, a drug that stabilizes breathing, may affect short-term potentiation. Eight stable patients with brain damage and 10 normal adults were studied. Activation of short-term potentiation was examined by brief exposure to hypoxia followed by hyperoxia after pretreatment with placebo or theophylline. Both in patients and normal subjects at the end of hypoxia ventilation increased to a similar magnitude with and without theophylline. In normal subjects independent of pretreatment, when hypoxia was terminated abruptly by hyperoxia, ventilation declined slowly to baseline without an undershoot, indicating activation of short-term potentiation. In patients with placebo, ventilation upon switching to hyperoxia exhibited a significant undershoot. This undershoot was significantly attenuated by theophylline, although compared with normal subjects, a slight hypoventilation was observed. We conclude that in patients with brain damage, theophylline largely prevents the hyperoxic drop of ventilation, presumably by affecting the activation of short-term potentiation. This may underlie the beneficial effect of theophylline on breathing stability.

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“…theophylline (Hedner et al, 1982;Eldridge et al, 1985). On the other hand, adenosine stimulates breathing in conscious, unanesthetised humans (Fuller et al, 1987;Griffith et al, 1997). The depressant effect of adenosine on breathing in vivo is more potent during the time period around birth and/or is also more severe in anesthetised animals (Herlenius et al, 2002).…”

Section: Ballanyi K Atp Channels In Brain Hypoxiamentioning

confidence: 99%

Protective role of neuronal KATP channels in brain hypoxia

Ballanyi

2004

Journal of Experimental Biology

127

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SUMMARY During severe arterial hypoxia leading to brain anoxia, most mammalian neurons undergo a massive depolarisation terminating in cell death. However,some neurons of the adult brain and most immature nervous structures tolerate extended periods of hypoxia–anoxia. An understanding of the mechanisms underlying this tolerance to oxygen depletion is pivotal for developing strategies to protect the brain from consequences of hypoxic-ischemic insults. ATP-sensitive K+ (KATP) channels are good subjects for this study as they are activated by processes associated with energy deprivation and can counteract the terminal anoxic-ischemic neuronal depolarisation. This review summarises in vitro analyses on the role of KATP channels in hypoxia–anoxia in three distinct neuronal systems of rodents. In dorsal vagal neurons, blockade of KATPchannels with sulfonylureas abolishes the hypoxic-anoxic hyperpolarisation. However, this does not affect the extreme tolerance of these neurons to oxygen depletion as evidenced by a moderate and sustained increase of intracellular Ca2+ (Cai). By contrast, a sulfonylurea-induced block of KATP channels shortens the delay of occurrence of a major Cai rise in cerebellar Purkinje neurons. In neurons of the neonatal medullary respiratory network, KATP channel blockers reverse the anoxic hyperpolarisation associated with slowing of respiratory frequency. This may constitute an adaptive mechanism for energy preservation. These studies demonstrate that KATP channels are an ubiquituous feature of mammalian neurons and may, indeed, play a protective role in brain hypoxia.

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The effect of dipyridamole and theophylline on hypercapnic ventilatory responses: the role of adenosine

Cited by 14 publications

References 30 publications

Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

Plasma Adenosine during Investigation of Hypoxic Ventilatory Response

Effects of Theophylline on Ventilatory Poststimulus Potentiation in Patients with Brain Damage

Protective role of neuronal KATP channels in brain hypoxia

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