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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An earlier study has demonstrated that indomethacin, a prostaglandin synthesis inhibitor, blocks the cerebrovascular response to hypercapnia. This response is believed to be mediated by a lowering of pH in the cerebral interstitial fluid. Should autoregulation of cerebral blood flow (CBF) to changing perfusion pressure also be mediated by a changing interstitial pH (the "metabolic" theory), then indomethacin should impair autoregulation. This hypothesis was tested in anesthetized baboons. CBF was measured by the intracarotid 133Xe clearance technique; the preparation and the indomethacin protocol were identical to those of our previous investigation. Arterial pressure was increased by the intravenous infusion of angiotensin and decreased by controlled hemorrhage. Indomethacin was given by continuous infusion into the internal carotid artery. Although it reduced resting CBF, the cerebrovascular response to changing perfusion pressure was unchanged. Because indomethacin affects the response to changing CO2 but not that to changing perfusion pressure, the mechanisms for these two reactions presumably are different and it is improbable that changing interstitial pH is responsible for autoregulation in the cerebral circulation.
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PMID:Response of the cerebral circulation in baboons to changing perfusion pressure after indomethacin. 40 29

Hypercapnia causes vasodilatation of retinal arterioles. Prostaglandin E1, injected close to retinal arterioles from the vitreal side cause vasodilatation apparently similar to that caused by hypercapnia. An inhibitor of prostaglandin synthase (indomethacin) was injected into the ocular circulation. There was a reversible inhibition of the retinal vasodilatation normally induced by hypercapnia. Indomethacin injected close to retinal arterioles from the vitreal side causes reversible vasoconstriction and inhibits the vasodilatory effect of hypercapnia. It is concluded that prostaglandin E1 satisfies three criteria for a candidate for a mediator of hypercapnia-induced arteriolar dilatation.
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PMID:[The role of prostaglandins in the regulation of retinal blood flow]. 225 Sep 34

Effects of topical application of hydrogen peroxide (H2O2) on pial arteriolar diameter and cerebral prostanoid synthesis were examined in newborn pigs. H2O2 (10 mM) caused initial constriction during the 1st min, followed by prolonged (20 min) dilation that was reversed on removal of the H2O2 in piglets treated with deferoxamine. H2O2 also caused an increase in cortical periarachnoid 6-ketoprostaglandin F1 alpha, thromboxane (TX) B2, and prostaglandin (PG) E2. Indomethacin pretreatment or coadministration of SQ 29548 (PGH2/TXA2 receptor antagonist) with H2O2 blocked the constriction due to H2O2 but did not alter the dilation. The constriction, the dilation, and the increased prostanoids caused by H2O2 were not affected by topical and systemic deferoxamine (an iron chelator) or simultaneous application of FeSO4 and FeCl3. Neither prior treatment with H2O2 nor with H2O2 plus FeSO4 and FeCl3 altered pial arteriolar dilation in response to hypercapnia. Therefore the initial constriction caused by H2O2 appears to result from stimulation of prostanoid synthesis and activation of PGH2/TXA2 receptors, whereas the dilation is not caused by prostanoids. H2O2 alone does not produce detectable residual alteration of pial arteriolar responsiveness or cerebral prostanoid synthesis.
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PMID:H2O2 effects on cerebral prostanoids and pial arteriolar diameter in piglets. 233 73

A prospective study on 150 infants with a birthweight of 1250 g or less was carried out to investigate the effects of patent ductus arteriosus (PDA), haemorrhagic pulmonary oedema (HPO), Indomethacin therapy and surgical ligation on the development of periventricular haemorrhage (PVH) or the extension of pre-existing PVH. The incidence of PVH, diagnosed by serial cerebral ultrasonography was 44% and the incidence of PDA, diagnosed by serial M-mode and contrast echocardiography, was 45%. During the first 8 days after birth when the infants were vulnerable to PVH, the development of PDA did not lead to the development or extension of PVH in 85% of infants. Haemorrhagic pulmonary oedema also had no effect on PVH in 71% of infants. Compared with infants whose PDA or HPO had no effect on PVH, those who had development or extension of haemorrhage had significantly more severe hypercapnia, blood gas instability and hypotension associated with the occurrence of PDA or HPO. Early Indomethacin therapy was not associated with the development or extension of PVH in 93% of infants. Although an elevation of arterial blood pressure was demonstrated after ductal ligation, surgery was performed after 1 week of age in all infants and in no instance was there an effect on PVH. This study suggests that PDA leads to PVH only if it causes significant blood gas and blood pressure disturbances which are known to affect cerebral blood flow adversely.
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PMID:Periventricular haemorrhage: association with patent ductus arteriosus and its treatment with indomethacin or surgery. 361 70

Cerebral blood flow (CBF) has been measured using a non-invasive Xenon133 clearance technique in six normal subjects after 2 days pretreatment with oral indomethacin at a dose of 100 mg/day. The results were compared with placebo given in a double blind balanced cross-over design. Indomethacin was found to result in a reduction in resting CBF of about 25% but the reactivity of the cerebrovascular circulation to carbon dioxide was preserved at normal levels. Infusions of epoprostenol (prostacyclin, PGI2) at a dose of 5 ng/kg/min resulted in a reduction of CBF of about 10% after placebo but no significant change in CBF after indomethacin. The results suggest that prostaglandins are involved in the maintenance of cerebrovascular tone but not in the mechanism of cerebral vasodilation accompanying hypercapnia. The combination of indomethacin and PGI2 has been proposed as a treatment of cerebral artery spasm and the findings suggest that the combination therapy would not be accompanied by undesirable intracerebral steal.
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PMID:Effect of indomethacin on cerebral blood flow, carbon dioxide reactivity and the response to epoprostenol (prostacyclin) infusion in man. 642 May 20

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.
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PMID:Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man. 659 1

Although results obtained in baboons and rats have demonstrated that the fatty acid cyclo-oxygenase inhibitor indomethacin reduces cerebral blood flow (CBF) under control conditions and markedly attenuates the CBF response to hypercapnia, nonconfirmatory results have been obtained in rabbits and cats. Since these latter studies were carried out under barbiturate anesthesia, we tested the effect of indomethacin (10 mg kg-1) on CBF and cerebral oxygen consumption in rats anesthetized with 150 mg kg-1 of phenobarbital. At normocapnia the barbiturate reduced CBF, measured with a 133Xe modification of the Kety-Schmidt technique, to about 50% of nitrous oxide control values as previously determined with a similar technique. At this CBF level, indomethacin induced a small, albeit highly significant decrease in CBF. We suggest that a reduction of this magnitude will escape detection with some CBF techniques in current use. Indomethacin induced a highly significant decrease in CBF during hypercapnia, demonstrating that the barbiturate does not eliminate the effect of indomethacin on CO2 responsiveness. The magnitude of the reduction in CO2 response was so large that is should be detected with most methods for measuring CBF. A comparison with previous data on animals under 70% N2O demonstrated that phenobarbital reduced the CO2 responsiveness. defined as the ratio deltaCBF/deltaPCO2, to 39% of that observed under nitrous oxide analgesia. With both types of anesthesia, indomethacin curtailed the CO2 responsiveness 4- to 5-fold.
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PMID:Effects of indomethacin on cerebral blood flow and oxygen consumption in barbiturate-anesthetized Normocapnic and hypercapnic rats. 732 33

The role of cyclic nucleotides and prostanoids in cerebrovascular reactivity to increased carbon dioxide was investigated in anesthetized and artificially ventilated newborn pigs equipped with closed cranial windows. Pial arteriolar diameter was measured, and cortical periarachnoid cerebrospinal fluid (CSF) was collected from beneath the cranial window for determination of adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and prostanoids. Progressively increasing arterial PCO2 (PaCO2) from normocapnia (33 +/- 1 mmHg) to hypercapnia (final PaCO2, 83 +/- 2 mmHg) resulted in dose-dependent pial arteriolar dilation and concomitant increases in cAMP, cGMP, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical CSF. N omega-methyl-L-arginine, N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester, methylene blue, and LY 83583 did not inhibit cerebral vasodilation or the increases in cortical cAMP/cGMP induced by hypercapnia. Indomethacin abolished the vasodilatory response to hypercapnia and attenuated the hypercapnia-induced increases in cAMP and cGMP. Prostacyclin analogues increased both cAMP and cGMP levels in cortical CSF and induced pial arteriolar dilation (iloprost > carbaprostacyclin). The present data suggest that in newborn pigs cyclic nucleotides are involved in cerebral vasodilation in response to hypercapnia via a prostanoid-dependent mechanism.
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PMID:CO2 and cerebral circulation in newborn pigs: cyclic nucleotides and prostanoids in vascular regulation. 751 62

The present study addresses the hypothesis that indomethacin, in addition to blocking prostaglandin synthesis, directly inhibits prostacyclin receptor-mediated cerebral vascular responses. To test this hypothesis, the effects of indomethacin on pial arteriolar dilation in response to the prostacyclin receptor agonist iloprost were investigated using a cranial window technique in newborn pigs. Topically applied iloprost resulted in dose-dependent pial arteriolar dilation and concomitant increases in cortical adenosine 3',5'-cyclic monophosphate (cAMP). Indomethacin (5 mg/kg iv + 10(-4) M topically) greatly reduced both the vasodilation and the increase in cortical cAMP in response to iloprost. In contrast, indomethacin did not attenuate beta-adrenoreceptor-mediated vasodilation and the increase in cortical cAMP in response to isoproterenol. Aspirin (50 mg/kg iv + 10(-3) M topically) did not affect pial arteriolar dilation or the increase in cortical cAMP in response to iloprost. Unlike indomethacin, aspirin was not effective in inhibiting prostanoid-associated cerebral vasodilation and increase in cortical cAMP in response to hypercapnia. The present data suggest that indomethacin selectively inhibits prostacyclin receptor-mediated responses in the newborn pig cerebral circulation. The combination of highly effective inhibition of prostaglandin H synthase and prostacyclin receptor-mediated vasodilation may contribute to the increased efficacy of indomethacin compared with other prostaglandin H synthase inhibitors in blocking certain vasodilator responses associated with prostanoids.
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PMID:Inhibitory effect of indomethacin on prostacyclin receptor-mediated cerebral vascular responses. 753 91

We investigated the effect of moderate (FiO2 13%) and light hypoxia (FiO2 17%) and hypercapnia (CO2 2-4%) with or without indomethacin on circulating levels of endothelin/endothelins (ET) and cerebral blood flow (CBF) in healthy volunteers. In protocol A, 23 subjects were exposed to moderate hypoxia. In protocol B, 29 subjects were randomized to one of four groups: (1) placebo, (2) indomethacin, (3) indomethacin+light hypoxia and (4) indomethacin+hypercapnia. Indomethacin was given as an intravenous bolus dose of 0.4mgkg-1 body weight followed by continuous infusion of 0.4mgkg-1h-1 for 6h. Two different FiO2 were chosen, light hypoxia in protocol B was chosen due to application of a known cerebral vasoconstrictor with unknown effect on cerebral autoregulation. We found, that moderate hypoxia (protocol A) induced a significant increase in CBF from 59.0 to 73.0 ml 100 g-1 brain tissue min-1 (p < 0.00005) with an increase in circulating levels of ET from 1.7 to 1.9fmol ml-1 plasma. However, this difference did not reach statistical significance (p = 0.14). We found, that indomethacin given intravenously (protocol B groups 2-3-4) significantly elevated circulating levels of ET from 2.1 to 3.9fmol ml-1 plasma (p < 0.00005) and decreased CBF from 60.5 to 39.5 ml 100g-1 brain tissue min-1 (p < 0.00005) compared to baseline values. Exposure to light hypoxia/hypercapnia in the indomethacin group increased CBF to values not significantly different from baseline values. Although there was no statistical correlation between ET and CBF with and without indomethacin, our results suggest that ET may be involved in the cerebral vasoconstriction produced by indomethacin given intravenously.
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PMID:Endothelin-1 and cerebral blood flow: influence of hypoxia, hypercapnia and indomethacin on circulating endothelin levels in healthy volunteers. 780 77


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