Role of adenosine in cerebral hypoxic hyperemia in the unanesthetized rabbit

Pinard, Elisabeth; Puiroud, Serge; Seylaz, Jacques

doi:10.1016/0006-8993(89)90492-7

Cited by 20 publications

(5 citation statements)

References 28 publications

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“…We also chose to use aminophylline, a nonspecific (both an A1 and A2) receptor antagonist. The range of depression in CBF (44% to 66%) in the WT mice, with and without MABP control, is similar to that observed in our earlier studies in the rat (Morii et al, 1987) as well as comparable with those noted by other investigators (Armstead, 1997;Emerson and Raymond, 1981;Hoffman et al, 1984;Pelligrino et al, 1995;Phillis et al, 1984;Pinard et al, 1989). We used aminophylline rather than the less-soluble theophylline to avoid volume overloading in mice.…”

Section: Pharmacological Considerationsupporting

confidence: 84%

Cerebral Blood Flow Response in Adenosine 2a Receptor Knockout Mice during Transient Hypoxic Hypoxia

Miękisiak

Kulik

Kusano

et al. 2008

J Cereb Blood Flow Metab

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We evaluated cerebral blood flow by laser Doppler during 30 secs of hypoxia (0.10 FiO(2)) in anesthetized, ventilated adenosine 2a receptor knockout (A2aR KO) and wild-type (WT) mice to test the hypothesis that cerebral hypoxic hyperemia in KO mice would be attenuated. We also studied the effects of selective and nonselective A2aR antagonists. During 30 secs of hypoxia, P(a)O(2) decreased significantly (P<0.05) and to a similar degree in both types of mice, whereas P(a)CO(2) remained relatively stable. However, mean arterial blood pressure (MABP) decreased to a greater extent (P<0.05) during hypoxia in KO mice (58.6+/-1.5 mm Hg) than in WT animals (76.1+/-3.2 mm Hg). Consequently, in a separate group of mice, we stabilized and matched MABP during hypoxia. Hypoxic hyperemia was attenuated by 38% (P<0.05) in KO animals whose MABP was uncontrolled, and by 81% (P<0.05) in KO animals whose MABP changes were matched to the MABP in the hypoxic WT mice. In animals treated with adenosine antagonists, hypoxic hyperemia was decreased by 44% to 48% (P<0.05) in WT mice, but was without effect in KO mice. We conclude that adenosine via A2aR is responsible for a significant proportion of the hyperemia during hypoxia.

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Section: Pharmacological Considerationsupporting

confidence: 84%

Cerebral Blood Flow Response in Adenosine 2a Receptor Knockout Mice during Transient Hypoxic Hypoxia

Miękisiak

Kulik

Kusano

et al. 2008

J Cereb Blood Flow Metab

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“…Moreover, theophylline produces no significant effect on hypercapnia-induced increase in CBF [68,69]. These results confirm the specificity of action of theophylline and other methylxan thines on hypoxia-induced adenosine release [68][69][70][71][72]75] and do not support a role for adenosine as a mediator of cerebral hypoxic hyperemia in the newborn piglet [74], How ever, the latter data on changes induced by methylxanthines in neonatal CBF rates dur ing hypoxia need further exploration. Like wise, theophylline significantly reduces the hyperemia observed during seizures in adult animals, prevents tissue hyperoxia and en hances brain damage.…”

Section: Effects Of Methylxanthines On Cerebral Blood Flow In Patholosupporting

confidence: 68%

“…In adult rats, rabbits and dogs, theophyl line has been shown to significantly attenuate or even block the increase in CBF recorded during moderate and severe hypoxia [68][69][70][71][72], whereas the methylxanthine does not in fluence either cerebral hypoxic hyperemia at the level of cerebrocortical microcirculation in adult cats [73] or hypoxia-induced increase in CBF in newborn piglets [74]. Moreover, theophylline produces no significant effect on hypercapnia-induced increase in CBF [68,69].…”

Section: Effects Of Methylxanthines On Cerebral Blood Flow In Patholomentioning

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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“…Brain and Spinal Cord. The hypothesis of Berne (1963) that adenosine is the physiologic regulator of reactive hyperemia was supported for the cerebral circulation by some authors (e.g., Winn et al, 1980;Emerson and Raymond, 1981;Kung et al, 2007) but not by others when the increase in blood flow that occurred in hypoxia was shown not to be clearly related to changes in adenosine concentration (Rehncrona et al, 1978;Heistad et al, 1981;Pinard et al, 1989). ATP, as well as adenosine, was measured in the perfusate of rat cerebral cortex during hypoxia (Phillis et al, 1993).…”

Section: Ischemiamentioning

confidence: 99%

“…However, evidence was later presented that questioned the hypothesis. For example, although theophylline, an adenosine receptor antagonist, blocked coronary vasodilation by perfused adenosine, it did not block reactive hyperemia (Rehncrona et al, 1978;Heistad et al, 1981;Pinard et al, 1989). It was also noted that although reactive hyperemia occurred after about 10 seconds, adenosine did not appear in the perfusate until about 90 seconds.…”

Section: Ischemiamentioning

confidence: 99%