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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of cyclooxygenase inhibition by indomethacin on regional cerebral blood flow (CBF) during hypocapnia induced by hyperventilation and during hypercapnia induced by CO2 inhalation was examined. CBF was measured in 27 anesthetized, ventilated piglets (2-8 d) using microspheres in control and indomethacin treated animals (5 mg/kg) after hyperventilation or inhalation of 6% CO2. In the control group (n = 6), CBF decreased significantly (p less than 0.05) to all regions of the brain after hyperventilation with a 32% decrease in the cerebral cortex. In the indomethacin-treated group (n = 6), blood flow significantly decreased by 35 to 49% in all regions of the brain, except the cerebral white matter, during normocapnia with no further decrease in flow during subsequent hypocapnia. Although CBF increased significantly after indomethacin treatment during hypercapnia the response was markedly attenuated with blood flow to the cerebral gray matter, hippocampus and pons rising only 42, 25, and 42% in contrast to 108, 75, and 225% in the control group. Since indomethacin decreased resting CBF, unilateral sympathetic nerve stimulation at 15 Hz was used to test the specificity of indomethacin on hypocapnic vasoconstriction (n = 5). Unilateral sympathetic nerve stimulation caused a further statistically significant decrease in CBF on the stimulated side after hyperventilation with indomethacin (12%), which was comparable to that which occurred during normocapnia (16%). The data demonstrate that indomethacin attenuates the cerebrovascular sensitivity to both increases and decreases in CO2/H+ and implicate a possible role for vasoactive prostanoids in mediating the response of CBF to fluctuations in CO2 in newborn piglets.
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PMID:Effect of indomethacin on the regulation of cerebral blood flow during respiratory alkalosis in newborn piglets. 251 48

Previous studies have shown that following experimental brain injury cerebral arterioles dilate and display endothelial lesions and reduced responsiveness to hypocapnia. These abnormalities are caused by cyclo-oxygenase-dependent free radical generation. There is evidence that the kallikrein-kinin system may in part stimulate the cyclooxygenase-dependent damage since bradykinin is a powerful stimulator of prostaglandin formation and it has recently been shown that a specific kinin receptor blocker decreases the arteriolar abnormalities caused by injury. In order to further examine the hypothesis that the kallikrein-kinin system is important in inducing damage, rat brain tissue was examined for kininogen, the precursor of kinins, at 10 minutes and 1, 3, 6, 15, 24, 48, and 72 hours after injury. A fluid-percussion brain injury device was attached over the right cerebral cortex of rats and a 1.6-atmosphere pressure injury was administered. The kininogen content was determined by a radioimmunoassay procedure in tissues which were free of intravascular blood. After injury, bleeding was confined mainly to the right hemisphere. The kininogen content in the right hemisphere was significantly elevated by one hour after injury, continued to rise until 15 hours after injury, then was significantly decreased by 2 days after injury. In the left hemisphere, kininogen was significantly elevated at 1 hour postinjury, returned toward control levels over the 3- to 6-hour period after injury, then was again elevated at 15 hours after injury. These studies also show that brain water and cerebrovascular permeability were greater at 15 hours postinjury than at earlier time points. The data further support a role for the kallikrein-kinin system in brain injury and, when considered with the results of other studies, suggest that a secondary event is occurring in the 12- to 24-hour period after neural injury. The authors hypothesize that this secondary event is related to endothelial and vascular repair and may be important for the return of normal cerebrovascular function.
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PMID:Brain kininogen following experimental brain injury: evidence for a secondary event. 276 94

Hypocapnia-induced constriction of peripheral airways may be important in regulating the distribution of ventilation in pathological conditions. We studied the response of the peripheral lung to hypocapnia in anesthetized, paralyzed, mechanically ventilated dogs using the wedged bronchoscope technique to measure resistance of the collateral system (Rcs). A 5-min hypocapnic challenge produced a 161 +/- 19% (mean +/- SE) increase in Rcs. The magnitude of this response was not diminished with repeated challenge or by atropine sulfate (1 mg base/kg iv), chlorpheniramine maleate (5 mg base/kg iv), or indomethacin (5 mg/kg iv). The response was reduced by 75% by isoproterenol (5 micrograms/kg iv) (P less than 0.01) and reduced by 80% by nifedipine (20 micrograms/kg iv) (P less than 0.05). During 30-min exposure to hypocapnia the maximum constrictor response occurred at 4-5 min, after which the response attenuated to approximately 50% of the maximum response (mean = 53%, range 34-69%). Further 30-min challenges with hypocapnia resulted in significantly decreased peak responses, the third response being 50% of the first (P less than 0.001). The inability of indomethacin or propranolol to affect the tachyphylaxis or attenuation of the response suggests that neither cyclooxygenase products nor beta-adrenergic activity was involved. Hence, hypocapnia caused a prompt and marked constrictor response in the peripheral lung not associated with cholinergic mechanisms or those involving histamine H1-receptors or prostaglandins. With prolonged exposure to hypocapnia there was gradual attentuation of the constrictor response with continued exposure and tachyphylaxis to repeated exposure both of which would tend to diminish any compensatory effect of hypocapnic airway constriction on the distribution of ventilation.
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PMID:Hypocapnia-induced constriction of the canine peripheral airways exhibits tachyphylaxis. 311 40

We studied the role of prostaglandins and free radicals in the induction of the functional and morphological pial arteriolar abnormalities produced by concussive brain injury. Anesthetized cats equipped with a cranial window for the observation of the pial microcirculation were subjected to concussive brain injury using a fluid-percussion device following administration of cyclooxygenase inhibitors (indomethacin or AHR-5850) or the vehicle for the solution of these agents (NaCl or Na2CO3 solution). Pial arterioles from vehicle-treated animals displayed sustained dilation, reduced responsiveness to the vasoconstrictor effect of arterial hypocapnia, and a high density of endothelial lesions. Animals pretreated with cyclooxygenase inhibitors showed less pronounced vasodilation, normal responsiveness to hypocapnia, and a significantly reduced number of lesions. The vasodilation and reduced responsiveness to the vasoconstrictor effects of hypocapnia after brain injury also were inhibited by topical application of free radical scavengers (nitroblue tetrazolium, superoxide dismutase, or mannitol). The vessels from cats pretreated with free radical scavengers also had a lower density of endothelial lesions than controls. The results support the view that the immediate cause of cerebral arteriolar damage in concussive brain injury is the generation of free oxygen radicals associated with increased prostaglandin synthesis.
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PMID:Inhibition by free radical scavengers and by cyclooxygenase inhibitors of pial arteriolar abnormalities from concussive brain injury in cats. 677 69

Acute severe hypertension induced by intravenous norepinephrine or angiotensin in anesthetized cats equipped with a cranial window caused prolonged arteriolar vasodilation associated with reduced responsiveness to arterial hypercapnia or hypocapnia and passive response to changes in arterial blood pressure. Scanning and transmission electron microscopy of such pial arterioles showed discrete destructive endothelial lesions the density of which correlated with the degree of vasodilation. Abnormalities of the vascular smooth muscle were seen in all dilated arterioles but affected only a small number of smooth muscle cells. The oxygen consumption of pial arterioles from cats subjected to hypertension was significantly reduced in comparison to that of vessels from normal animals. The arteriolar abnormalities induced by hypertension were inhibited by pretreatment with inhibitors of cyclooxygenase (indomethacin or AHR-5850) or by topical application on the brain surface of scavengers of free oxygen radicals (mannitol or superoxide dismutase). The results suggest that the mechanism of the arteriolar abnormalities from acute hypertension involves a sudden increase in prostaglandin synthesis that leads to generation of free oxygen radicals.
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PMID:Mechanism of cerebral arteriolar abnormalities after acute hypertension. 722 3

The most abundant prostaglandin produced by brain tissue varies from species to species. The most abundant prostaglandin produced by brain microvessels is PGI2, PGG2, PGH2, PGI2, PGE2, PGD2, and arachidonic acid dilated cerebral arterioles. Cyclooxygenase inhibitors (indomethacin, AHR-5850), in doses that reduced prostaglandin synthesis substantially, did not affect resting vascular caliber and did not influence the responses of cerebral arterioles to arterial hypoxia, arterial hypercapnia, or arterial hypocapnia, suggesting that prostaglandins are not involved in the mediation of these responses. The vasodilator action of vasoactive intestinal peptide on cerebral arterioles was blocked by these cyclooxygenase inhibitors. The cerebral arteriolar damage induced by fluid-percussion brain injury was inhibited by pretreatment with cyclooxygenase inhibitors, or with free radical scavengers. Topical application of arachidonic acid or PGG2, reproduced the damage seen with brain injury. These findings show that prostaglandins are mediators of the cerebral arteriolar damage due to brain injury and that their mechanism of action is dependent on the generation of free oxygen radicals.
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PMID:Prostaglandins in physiological and in certain pathological responses of the cerebral circulation. 723 14

A canine model of exercise-induced asthma was used to test the hypothesis that the development of a late phase response to hyperventilation depends on the acute production of pro-inflammatory mediators. Peripheral airway resistance, reactivity to hypocapnia and aerosol histamine, and bronchoalveolar lavage fluid (BALF) cell and eicosanoid content were measured in dogs approximately 5 h after dry air challenge (DAC). DAC resulted in late phase obstruction, hyperreactivity to histamine, and neutrophilic inflammation. Both cyclooxygenase and lipoxygenase inhibitors administered in separate experiments attenuated the late phase airway obstruction and hyperreactivity to histamine. Neither drug affected the late phase inflammation nor the concentrations of eicosanoids in the BALF obtained 5 h after DAC. This study confirms that hyperventilation of peripheral airways with unconditioned air causes late phase neutrophilia, airway obstruction, and hyperreactivity. The late phase changes in airway mechanics are related to the hyperventilation-induced release of both prostaglandins and leukotrienes, and appear to be independent of the late phase infiltration of inflammatory cells.
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PMID:Eicosanoids modulate hyperpnea-induced late phase airway obstruction and hyperreactivity in dogs. 1178 38

The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR(O(2))) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR(O(2)) in five, young healthy volunteers before and during COX inhibition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR(O(2)) changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.
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PMID:Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition. 1581 83