Effects of aminophylline on hypoxemia-induced ventilatory depression in the cat

Javaheri, Shahrokh; Teppema, L.J.; Evers, J.A.M.

doi:10.1152/jappl.1988.64.5.1837

Cited by 30 publications

(17 citation statements)

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“…The fact that the increase in respiratory frequency was smaller after both drugs can be explained as a direct consequence of the increase in respiratory cycle length. These observations are consistent with published reports that theophylline or aminophylline can ameliorate the secondary respiratory depression caused by hypoxia in several species, including neonate pig, adult cat and man (Millhorn, Eldridge, Kiley & Waldrop, 1984;Darnall, 1985;Easton & Anthionsen, 1988;Javaheri, Teppema & Evers, 1988). There is much evidence that methylxanthines stimulate respiration predominantly by an action within the central nervous system, probably within the brain stem, on neuronal adenosine receptors (Eldridge et al 1985).…”

Section: Effects Of Theophylline and 8-phenyltheophylline In Normoxiasupporting

confidence: 91%

The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.

Neylon¹,

Marshall²

1991

The Journal of Physiology

104

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SUMMARY1. In rats anaesthetized with Saffan we have studied the effects of the adenosine receptor antagonists, theophylline and 8-phenyltheophylline, upon the respiratory and cardiovascular responses evoked by 5 min periods of systemic hypoxia.2. In the group of animals that were to receive theophylline (15 mg kg-' i.v.), arterial 02 pressure (Pal 02) fell from 83 + 2 mmHg during air breathing to 38 + 3 or 34 + 3 mmHg during the 5th minute of two different control periods of hypoxia, while in the group that were to receive 8-phenyltheophylline (10 mg kg-' i.v.), Pa 02 fell from 83 + 1 to 53 + 2 mmHg. Neither drug significantly altered the levels of Pa, 2 reached during hypoxia. 3. During the control periods of hypoxia respiration increased, but the increase evoked at the 5th minute was significantly less than that evoked at the 2nd minute of hypoxia. This secondary waning of the hyperventilation was abolished by both drugs.4. Similarly, both drugs attenuated the tendency for the hypoxia-induced tachyeardia to wane between the 2nd and 5th minute.5. Further, both drugs substantially reduced both the hypoxia-induced fall-in arterial pressure and the increases in vascular conductance in hindlimb muscle, carotid vasculature and kidney.6. Thus, we propose that in the rat the release of adenosine by hypoxic tissues makes a major contribution to the secondary decrease in respiration and heart rate that occurs during systemic hypoxia and to the accompanying vasodilatation in muscle and fall in arterial pressure. The effects of the adenosine antagonists on the carotid and renal vasculature are more equivocal and may be partly explained as a smaller autoregulatory dilatation to a smaller fall in systemic arterial pressure.7. These results and proposals are discussed in relation to the conditions that are known to cause release of adenosine and in relation to its known effects upon the respiratory and cardiovascular systems.

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Section: Effects Of Theophylline and 8-phenyltheophylline In Normoxiasupporting

confidence: 91%

The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.

Neylon¹,

Marshall²

1991

The Journal of Physiology

104

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“…An increase in tidal volume (without change in respiratory frequency) was thought to be due to the competition with adenosine at some of its central receptor sites [17]. In the present investigation, it seems likely that theophylline activated central respiratory receptors and reversed the hypoxic ventilatory depression [18]. This resulted in a more in-phase response of ventilation to altered blood gases with consecutive reduction of periodic breathing [19,20].…”

Section: Discussionmentioning

confidence: 56%

Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude

Fischer¹,

Lang²,

Leitl³

et al. 2003

Eur Respir J

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Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude. R. Fischer, S.M. Lang, M. Leitl, M. Thiere, U. Steiner, R.M. Huber. #ERS Journals Ltd 2004. ABSTRACT: A randomised, double-blind, placebo-controlled study was conducted to evaluate the effects of theophylline and acetazolamide in the treatment of sleepdisordered breathing (SDB) after fast ascent to high altitude (3,454 m).The study was conducted at a high-altitude research laboratory and included 30 healthy male volunteers. Study medication was either oral slow release theophylline (26250 mg?day -1 ), oral acetazolamide (26250 mg?day -1 ) or a matched placebo tablet. Polysomnographic measurements were performed during two consecutive nights, and acute mountain sickness, pulse rate, oxyhaemoglobin saturation and arterial blood gases were assessed three times a day.Without active medication, the apnoea/hypopnoea index (AHI) was highly pathological ( Sleep-disordered breathing (SDB) of the Cheyne-Stokes type is commonly found during sleep at high altitude [1][2][3]. This typical breathing pattern with waxing and waning of the tidal volume is associated with profound desaturations and reduced overall oxygen saturation during sleep, but its association with an increased number of arousals is a matter of ongoing debate [4,5]. The use of acetazolamide at high altitude is known to reduce the time spent with periodic breathing, to improve overall oxygen saturation during sleep and to reduce the number of arousals [6].Acetazolamide inhibits the renal enzyme carbonic anhydrase, which leads to metabolic acidosis, and, as a result, increases ventilation and oxygenation. The beneficial effects of this drug at high altitude are thought to be due to this improved oxygenation. Although serious side-effects of acetazolamide are uncommon, an alternative treatment option would be desirable for patients with known sulphonamide intolerance. In a previous, prospective, randomised study, the authors were able to show that theophylline has a positive impact on symptoms of acute mountain sickness (AMS), compared with placebo [7]. As theophylline was shown to be effective in reducing periodic breathing in premature newborns and in patients with severe heart failure [8, 9], a similar effect in high-altitude periodic breathing could be assumed.Therefore, a randomised, double-blind, placebo-controlled study was conducted to evaluate the effect of theophylline and acetazolamide on periodic breathing and arterial oxyhaemoglobin desaturations during sleep at high altitude. The aims were to compare the efficacy of theophylline and acetazolamide in normalising high-altitude SDB and in decreasing nocturnal oxyhaemoglobin desaturation. Methods Study populationHealthy male volunteers (n=30) gave informed written consent to participate in the study. Of 30 subjects, 22 were engaged in regular mountaineering activities in their spare time, but none of them had experienced altitudes above 3,500 m. The study protocol was approved by the local ethics committee. Exclusion cr...

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“…The decrease in ventilation of chemodenervated animals during hypoxia was attributed to an increase in cerebral blood flow and the consequent decrease in cerebrospinal fluid PCO 2 [11] and to the release of inhibitory neurotransmitters [12,13,16]. However, studies by Javaheri et al [17] on chemodenervated-vagotomized animals have shown that hypoxic ventilatory depression occurs both in the face of a rise or a fall in ventral medullary extracellular fluid PCO 2 and H + and is prevented by aminophylline.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, hypoxia influences the rate of synthesis or release of neurotransmitters and modulators [12,13], leading to accumulation of adenosine, dopamine and Á-aminobutyric acid in the brain [2,14,15]. Administration of long-acting analogues of adenosine, either systemically or directly into the third cerebral ventricle, decreases phrenic nerve activity in peripherally chemodenervated air breathing cats while theophylline, a specific antagonist of adenosine, prevents and reverses the decrease of phrenic activity [16] as reported by Javaheri et al [17]. These studies [16,17] clearly show the important role of adenosine in the central depressant effect of hypoxia in respiration in chemodenervated animals.…”

Section: Introductionmentioning

confidence: 99%

Effects of Intravenous and Intracerebroventricular Theophylline on Hypoxic Ventilatory Depression in Anesthetized Cats

et al. 2004

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Objective: The present study was undertaken to investigate the ventilatory response due to sustained isocapnic moderate hypoxia and the possible role of adenosine in hypoxic depression in anesthetized cats. Materials and Methods: Cats anesthetized with pentothal sodium (30 mg kg^–1 i.p.) were divided into two groups: treated (n = 11) and control (n = 15). Respiratory frequency (f), tidal volume (V_T), minute volume (v̇E) and systemic arterial blood pressure were recorded during air and 20 min of breathing hypoxic gas mixture (14% O₂-86% N₂). Isocapnia was maintained by adding fractions of 1% CO₂ to the inspired hypoxic gas mixture. The PaO₂ and PaCO₂ were determined. Results: On hypoxic gas mixture breathing, V_Tand v̇E values of the control animals increased significantly, at 5 min to 50 ± 6 and 53 ± 6%, respectively, above the prehypoxic air phase value (p < 0.001). After that, the magnitude of increase in V_T and v̇E declined gradually. At 20 min of hypoxia, V_T and v̇E were less than those in prehypoxic air phase (17 ± 7, 16 ± 7%, respectively). In cats injected with an adenosine antagonist (theophylline 13.6 mg kg^–1 i.v.), f, V_T and v̇E increased significantly at 5 min of hypoxia (p < 0.001). At 20 min of hypoxia, f, V_T and v̇E were 8 ± 2, 30 ± 8, and 39 ± 8%, respectively, higher than corresponding values of the prehypoxic stage. In cats injected with theophylline (0.5 mg kg^–1) by cisternal puncture V_T and v̇E increased significantly at 5 min of hypoxia. At 20 min of hypoxia, V_T and v̇E were 27 ± 7 and 31 ± 8% higher than those in the prehypoxic air phase. Conclusion: The results of this study show that accumulation of adenosine in the brain during hypoxia seems to reduce the response of the central mechanisms to chemoreceptor impulses.

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Effects of aminophylline on hypoxemia-induced ventilatory depression in the cat

Cited by 30 publications

References 0 publications

The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.

The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.

Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude

Effects of Intravenous and Intracerebroventricular Theophylline on Hypoxic Ventilatory Depression in Anesthetized Cats

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