Effect of Aminophylline on Brain Blood Flow in the Newborn Piglet

Stonestreet, Barbara S.; Nowicki, Ph.T.; Hansen, Nancy B.; Petit, R; Oh, William

doi:10.1159/000457311

Cited by 16 publications

(9 citation statements)

References 9 publications

(27 reference statements)

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“…These findings agree with those from a comparable study in piglets given 6 mg/kg theophylline ethylenediamine (25) and argue against a direct cerebral vascular or metabolic effect of theophylline at this dose.…”

Section: Discussionsupporting

confidence: 90%

The Effect of Theophylline on Regional Cerebral Blood Flow Responses to Hypoxia in Newborn Piglets

McPhee

Maxwell

1987

Pediatr Res

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ABSTRACT. Theophylline attenuates cerebral hypoxic hyperemia in several adult models and this is thought to be due to receptor-mediated antagonism of adenosine, a proposed mediator of hypoxic hyperemia. This attenuation of hypoxic hyperemia reduces cerebral oxygen delivery and mav thus ieo~ardize cerebral oxidative metabolism. With these con~de~ations in mind, and because theophylline is widely used in neonatal medicine, the present study was designed to investigate the effect of theophylline on regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate for oxygen during normoxia and hypoxia in the newborn piglet model. In 16 newborn piglets, regional cerebral blood flow (microspheres) increased 250-350% during hypoxia (Pa02 20-30 torr), while cerebral oxygen delivery and cerebral metabolic rate for oxygen were maintained at normoxic levels. Eight of these piglets were then given 10 mg/kg theophylline ethylenediamine intravenously and studies during normoxia and hypoxia were repeated; the remaining eight piglets served as time controls. Regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate for oxygen during normoxia and hypoxia were not influenced by theophylline, despite plasma theophylline levels of 55-65 pmol/liter, and cerebrospinal fluid theophylline levels of 30-40 pmol/liter. These negative results are reassuring with respect to hypoxic cerebral blood flow control in theophylline-medicated infants. However, they do not support a role for adenosine as a mediator of cerebral hypoxic hyperemia in this model. (Pediatr Res 21: 573-578, 1987) Abbreviations CBF, cerebral blood flow COD, cerebral oxygen delivery CMR02, cerebral metabolic rate for oxygen MAP, mean arterial pressure SSP, sagittal sinus pressure CPP, cerebral perfusion pressure ANOVA, analysis of variance Theophylline is used widely in neonatal medicine, its uses include the treatment of apnea of prematurity (1, 2), the treatment of bronchopulmonary dysplasia (3), and the facilitation of weaning from mechanical ventilation (4-6). Several studies in adult models have shown that theophylline attenuates CBF re-

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Section: Discussionsupporting

confidence: 90%

The Effect of Theophylline on Regional Cerebral Blood Flow Responses to Hypoxia in Newborn Piglets

McPhee

Maxwell

1987

Pediatr Res

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“…The constancy of the angle of insonation is not easily achieved with this method. On the contrary, using the newborn piglet un der conditions of controlled ventilation to maintain a constant Pco2> Stonestreet et al [5] showed that a therapeutic dose of ami nophylline (6 mg/kg) did not alter CBF. McPhee and Maxwell [8] confirmed these findings with theophylline (10 mg/kg) in the same animal model.…”

Section: Discussionmentioning

confidence: 98%

“…If renal, cardiovascular and gastrointesti nal side effects of these drugs are well docu mented [2,3], few studies have examined the effects of aminophylline on the developing brain [4,5], However, there is some evidence that, in adults, aminophylline and caffeine reduce cerebral blood flow (CBF). CBF was measured with either the xenon-133 inhala tion technique, or the xenon-133 intracarot id injection method [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Caffeine on Cerebral Blood Flow Velocity in Preterm Infants

Saliba¹,

Autret²,

Gold³

et al. 1989

Neonatology

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A continuous-wave form Doppler monitor was used to examine the effect of caffeine on cerebral blood flow velocity (CBFV) in 7 clinically stable preterm neonates suffering from apnea. Caffeine, in the form of caffeine citrate, or saline were given intravenously at loading doses of 20 mg/kg. Every subject was his own control. Placebo (saline) was systematically injected prior to caffeine citrate. Simultaneous recording of heart rate, arterial blood pressure, respiratory rate, TcP_O2, TcP_CO2 were made before, then at the end of the injection, and 30, 60 and 120 min after the end of each administration of either placebo or caffeine. Compared with placebo, caffeine injection was not associated with significant changes in CBFV. An increase was found in both heart-rate and respiratory rate (p < 0.05). Mean arterial blood pressure, TcP_O2 and TcP_O2 did not change significantly. Our data suggest that a caffeine citrate loading dose of 20 mg/kg as currently used at the beginning of treatment of apnea in preterm neonates has no effect on CBFV.

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“…Indeed, hypocapnia has been recorded after methylxanthine administra tion in both preterm neonates [60,66] and in adult animals [28-32] and humans [35]. The decrease in CBF can be avoided and thus methylxanthine safely used in the treatment of apnea of prematurity when pCCF is moni tored and maintained at a constant level [67],…”

Section: Effects O F M Ethylxanthines On Cerebral Blood Flow and Metamentioning

confidence: 99%

Effects of Respiratory Stimulants on Cerebral Metabolism and Blood Flow

Nehlig¹

1994

Neonatology

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The cerebral metabolic and circulatory effects of the two main classes of respiratory stimulants used in the apnea of the newborn and premature infant, i.e. methylxanthines and doxapram, have not been studied in great detail. In adult animals and humans, methylxanthines widely increase cerebral metabolic rates and simultaneously decrease cerebral blood flow levels. Thus, these compounds are able to reset the level of coupling between cerebral blood flow and energy metabolism inducing a relative hypoperfusion at a constant metabolic rate. In neonates, methylxanthines induce no change in cerebral blood flow as long as the drop in pCO₂ related to drug administration is prevented. Information on doxapram effects on cerebral blood flow and metabolism is very scarse and limited to adult animals. Doxapram does not induce any change in cerebral energy metabolism and transiently decreases cerebral blood flow. In conclusion, it seems that the use of methylxanthines in apneic newborn infants fulfils a good margin of safety with respect to cerebral blood flow as long as no other pathology such as marked hypoxia or seizures is present. The use of doxapram also seems to stay in a good margin of safety in terms of cerebral blood flow and energy metabolism but many more studies are necessary to better understand the effects of this respiratory stimulant on cerebral functional activity.

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Effect of Aminophylline on Brain Blood Flow in the Newborn Piglet

Cited by 16 publications

References 9 publications

The Effect of Theophylline on Regional Cerebral Blood Flow Responses to Hypoxia in Newborn Piglets

The Effect of Theophylline on Regional Cerebral Blood Flow Responses to Hypoxia in Newborn Piglets

Effect of Caffeine on Cerebral Blood Flow Velocity in Preterm Infants

Effects of Respiratory Stimulants on Cerebral Metabolism and Blood Flow

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