Effect of indomethacin on basal and carbon dioxide stimulated cerebral blood flow in man

Abstract

Summary. Cerebral blood flow (CBF) was measured using the nitrous oxide technique in the basal state and following inhalation of CO2 in eight, healthy, awake male volunteers, before and during inhibition of prostaglandin synthesis with indomethacin. Arterial and jugular venous oxygen contents and pCO2 were also analysed. Indomethacin reduced the basal CBF by 35%, from 43 ± 2 to 28 ± 2 ml/100 ml tissue per min, but did not affect the calculated cerebral metabolic rate of oxygen (CMRO2). The reduced CBF was accompanied by an elevation of jugular venous pCO2. Inhalation of 6–7% CO2 increased CBF to 98 ± 17 ml/100 ml tissue per min before indomethacin, compared with only 42 ± 4 ml/100 ml tissue per min after indomethacin. This difference in the hypercapnia induced increase in CBF before and after indomethacin was reflected also by the data on arterio‐venous differences in pCO2. We conclude that indomethacin inhibits both basal and hypercapnia stimulated CBF in man and suggest that this effect of the drug is due to inhibition of prostaglandin formation. If so, cerebral vascular PG formation plays an important role not only in the maintenance of CBF during normocapnia, but also in the cerebral vasodilation associated with elevated arterial pCO2.

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

“…The average reduction of CBF was 35%. Similar reductions were found in previous human studies using indirect methods (Wennmalm et al, 1981;Hemler et al, 1990;Jensen et al, 1993Jensen et al, , 1996. The findings are also similar to the result of the only previous tomographic study showing 28% to 40% reduction of CBF in baboons, depending on the region (Schumann et al, 1996).…”

“…The only tomographic study on living animals (Schumann et al, 1996), found no change of the global CMR O 2 but interestingly (see below) a small and significant increase of CMR O 2 in thalamus and pons. In adult humans, the effect of indomethacin on CMR O 2 was assessed only by the arterio-venous difference (Wennmalm et al, 1981;Jensen et al, 1991;Dahl et al, 1996;Bundgaard et al, 1996) and no significant change was observed in any of these studies. However, a study of preterm infants with near-infrared-spectroscopy of cytochrome oxidase indicated reduced oxygenation (Benders et al, 1995).…”

Can Treatment of Patent Ductus Arteriosus with Ibuprofen Compared to Supportive Management Affect Regional Brain Volume in Very Low Birth Weight Infants? A Pilot Study

“…in 1981 also found the same results when indomethacin was administered in adults 18) , and a study of neonates by Evans et al…”

Role of Prostaglandins in the Response of the Cerebral Circulation to Carbon Dioxide in Conscious Rabbits

“…Recently, several laboratories have reported biochemical determinations of prostaglan dins in brain or cerebral venous blood during changes in arterial PC02 ' Ellis et al (1982) found that pros taglandin E2 and F2rr levels in brain tissue actually decreased from normocapnia levels when cats were exposed to hypercapnia, while 6-keto-F 1rr did not change and pial arterial diameter increased 32%. In addition, in preliminary reports, McCalden et al (1982) and Wennmalm et al (1982) found that pros tacyclin levels in cerebral venous blood, in baboons and humans, respectively, did not increase from control levels during hypercapnia, whereas CBF in creased. Thus, biochemical determinations of pros taglandins during hypercapnia confirm pharmaco logical studies.…”