The Effect of Circulating Adenosine on Cerebral Haemodynamics and Headache Generation in Healthy Subjects

Abstract

Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design. Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (V(MCA)) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 microg kg(-1) min(-1) and six during 120 microg kg(-1) min(-1) compared with none on placebo (P = 0.006). The headache was very mild and predominantly described as a pressing sensation. When correcting data for adenosine-induced hyperventilation, no significant changes in rCBF (P = 0.22) or V(MCA) (P = 0.16) were found between treatments. A significant dilation of the superficial temporal artery (STA) was seen (P < 0.001). These results show that circulating adenosine has no effect on rCBF or V(MCA), while it dilates the STA and causes very mild headache.

Comparison of the Effects of Adenosine, Inosine, and Their Combination as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction

“…In a first series of 5 animals (all excluded from the ACS protocol), carotid blood flow measurements were used to determine which dose in the rat induces maximal carotid blood flow and correlates to the dose described in the man, that is, 120–140  μ g/kg/mn [12, 13]; from there the dosage that in the rat approximately corresponds to adenosine 50–70  μ g/kg/mn, as had been IV given to patients with ACS in several human trials [14–16], was easy to estimate. We used starting doses drawn from the data published by Ohnishi et al [17] about the effect of adenosine on blood pressure measured at the carotid artery level in the normotensive rat, because no reference specifically focused on CaBF after adenosine administration could be found in the literature with this animal.…”

Role of Adenosine and Nitric Oxide on the Mechanisms of Action of Dipyridamole

“…Results from these studies are confounded by the prominent increase in ventilation, as a result of arterial chemoreceptors activation 34 and in sympathetic activity 35 produced by adenosine. After correcting for adenosine-induced hyperventilation, Birk et al found that systemic administration of adenosine did not increase cerebral blood flow, 36 but the effect of dipyridamole on cerebral blood flow autoregulation has not been defined.…”

Sources of Variability of Resting Cerebral Blood Flow in Healthy Subjects: A Study Using133Xe SPECT Measurements

“…[7][8][9][10][11][12][13][14][15][16][17][18][19] All measurements were performed using the same gamma camera and identical acquisition and processing protocols.…”