RESUMEN
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.
Asunto(s)
Adenosina/administración & dosificación , Adenosina/sangre , Circulación Cerebrovascular/efectos de los fármacos , Cefalea/fisiopatología , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Circulación Cerebrovascular/fisiología , Estudios Cruzados , Método Doble Ciego , Femenino , Cefalea/inducido químicamente , Humanos , Infusiones Intravenosas , MasculinoRESUMEN
BIBN4096BS is a CGRP-antagonist effective in the treatment of migraine. Blocking the receptor of a strong vasodilator involves a theoretical risk of causing cerebral vasoconstriction, a probability not previously investigated with BIBN4096BS. Seven healthy volunteers completed this double-blinded placebo-controlled crossover study. The volunteers received randomly 10 min infusions of either placebo, 2.5 mg or 10 mg of BIBN4096BS on 3 separate days. Transcranial Doppler was used to measure the middle cerebral artery blood flow velocity (V(MCA)); global and regional cerebral blood flow (rCBF(MCA)) was measured by 133-Xenon inhalation SPECT. The diameter of the temporal and radial artery was measured by high-resolution ultrasound. Systemic haemodynamics and partial pressure of CO(2) (P(et)CO(2)), and adverse events were monitored regularly. BIBN4096BS had no influence on global or regional cerebral blood flow, or on the blood flow velocity in the middle cerebral artery. There was no effect on systemic haemodynamics and adverse events were minor. We conclude that there is no effect of CGRP-receptor blockade on the cerebral or systemic circulation in humans. Circulating CGRP is therefore not likely to exert a vasodilatory activity in the resting state and the use of BIBN4096BS for acute migraine seems to be without risk of cerebral vasoactivity. These data suggest that BIBN4096BS is the first specific antimigraine drug without vasoactive effect.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Encéfalo/irrigación sanguínea , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Circulación Cerebrovascular/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Piperazinas/farmacología , Quinazolinas/farmacología , Adulto , Femenino , Humanos , Masculino , Flujo Sanguíneo Regional/efectos de los fármacosAsunto(s)
Circulación Cerebrovascular , Síndrome del Cromosoma X Frágil/diagnóstico por imagen , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/diagnóstico por imagen , Adolescente , Adulto , Niño , Preescolar , Femenino , Síndrome del Cromosoma X Frágil/fisiopatología , Humanos , Lactante , Masculino , Proyectos Piloto , Tecnecio , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
This study was designed to determine the influence of cold-air inhalation on regional myocardial perfusion in patients with ischemic heart disease. A selected group of vasoactive hormones was measured to investigate their possible roles as ischemic agents. Ten men who had recently had a myocardial infarction and anginal symptoms and with verified pathologic ST deviations during a preceding exercise test volunteered to participate in this randomized cross-over study. Two identical exercise tests were performed on different days; one with inhalation of cold (-22 degrees C) air and the other one with inhalation of thermoneutral air (22 degrees C). Scintigraphic imaging (single-photon emission computed tomography) of regional myocardial blood flow was performed with technetium 99m isonitrile flowtracer and a Bull's eye visual display with calculation of the scintigraphic ischemic severity score. The score was significantly higher during exercise with inhalation of cold air as compared to exercise with inhalation of thermoneutral air. Furthermore, only with cold-air inhalation did arterial plasma endothelin concentration increase significantly from rest to exercise and correlate with the change of ischemic severity score. In contrast, no change was observed under thermoneutral conditions. There was no significant difference between peak values of heart rate, systolic blood pressure, adrenaline, and noradrenaline concentrations in the two situations. We conclude that inhalation of cold air during exercise increases the degree of regional myocardial ischemia and that this is not caused by an increased myocardial oxygen demand. We suggest that cold air directly influences the vasomotor tone of the myocardial resistance vessels and that endothelin may be involved in the ischemic response.