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

The effect of the cyclooxygenase inhibitor, indomethacin, on choroidal (ChBF) and retinal (RBF) blood flow during hypercarbia was examined in 16 paralyzed and mechanically ventilated piglets less than 8 d old. The animals were randomly assigned to a control group (mean +/- SEM: wt, 1.66 +/- 0.1 kg; n = 8) that received a placebo infusion or to an indomethacin treatment group (wt, 1.68 +/- 0.2 kg; n = 8) that received an infusion of indomethacin (5 mg/kg i.v. over 30 min). Baseline ChBF and RBF were measured using radiolabeled microspheres in room air before and 15 min after the administration of placebo or indomethacin. Animals were then exposed to 30 min of hypercarbia (6-7% CO2, arterial CO2 pressure 8-10 kPa) and measurements were repeated. There were no significant differences in RBF between control (40 +/- 3 mL/min/100 g) and indomethacin-treated animals (40 +/- 3 mL/min/100 g) before administration of placebo or indomethacin. However, RBF decreased significantly in the indomethacin-treated animals (28 +/- 2 mL/min/100 g) compared to the control group (42 +/- 4 mL/min/100 g) 15 min after administration of placebo or indomethacin. Furthermore, an increase in RBF occurred during hypercarbia in the control group (86 +/- 6 mL/min/100 g), but this change was blunted in the indomethacin-treated animals (33 +/- 5 mL/min/100 g) (p less than 0.001). In contrast, ChBF did not differ significantly between the control and indomethacin groups during the periods studied. These results suggest that the increase in RBF during hypercarbia is at least partially mediated by cyclooxygenase by-products of arachidonic acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of cyclooxygenase inhibition on retinal and choroidal blood flow during hypercarbia in newborn piglets. 154 39

In newborn pigs, cerebral ischemia abolishes both increased cerebral prostanoid production and cerebral vasodilation in response to hypercapnia and hypotension. Attenuation of prostaglandin endoperoxide synthase activity could account for the failure to increase prostanoid synthesis and loss of responses to these stimuli. To test this possibility, arachidonic acid (3, 6, or 30 micrograms/ml) was placed under cranial windows in newborn pigs that had been exposed to 20 min of cerebral ischemia. The conversion to prostanoids and pial arteriolar responses to the arachidonic acid were measured. At all three concentrations, arachidonic acid caused similar increases in pial arteriolar diameter in sham control piglets and piglets 1 hr postischemia. Topical arachidonic acid caused dose-dependent increases of PGE2 in cortical periarachnoid cerebral spinal fluid. 6-keto-PGF1 alpha and TXB2 only increased at the highest concentration of arachidonic acid (30 micrograms/ml). Cerebral ischemia did not decrease the conversion of any concentration of arachidonic acid to PGE2, 6-keto-PGF1 alpha, or TXB2. We conclude that ischemia and subsequent reperfusion do not result in inhibition of prostaglandin endoperoxide synthase in the newborn pig brain. Therefore, the mechanism for the impaired prostanoid production in response to hypercapnia and hypotension following cerebral ischemia appears to involve reduction in release of free arachidonic acid.
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PMID:Prostanoid synthesis and vascular responses to exogenous arachidonic acid following cerebral ischemia in piglets. 212 54

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

We studied the effect of systemic hypoxemia and hypercarbia on the bronchial blood flow in open-chested, anesthetized dogs. The pulmonary artery and vein of the left lower lobe (LLL) were isolated with cannulas and connected to reservoirs set at atmospheric pressure relative to the base of the LLL. That fraction of the bronchial arterial flow (Qbr) to the LLL, which flowed through the bronchopulmonary anastomoses into these reservoirs, was continuously measured. The LLL was inflated continuously with 6% CO2 and air at a constant alveolar pressure of 10 cm H2O. Systemic arterial O2 tension (PaO2) and arterial CO2 tension (PaCO2) were varied by separately ventilating the right lung through a bifurcated endotracheal tube. A 10-min period was allowed for stabilization after each change in experimental condition. Anastomotic Qbr was measured for 5 min during each experiment. In separate animals, similar studies were performed before and 30 min after intravenously administered indomethacin (6 mg/kg body weight). During normoxic conditions when PaO2 was 79 +/- 8 torr (mean +/- SEM), the mean anastomotic Qbr was 5.7 +/- 2.0 ml/min (n = 9). This flow increased to 8.3 +/- 2.5 ml/min (p less than 0.05) during hypoxemic conditions (PaO2, 38 +/- 3). The anastomotic Qbr increased from 5.8 +/- 1 to 9.0 +/- 2 ml/min (p less than 0.005) when PaCO2 was increased from 23 +/- 1 to 47 +/- 2 torr (n = 11). Pretreatment with intravenously administered indomethacin blocked both the hypoxemia-induced (n = 4) and hypercarbia-induced (n = 4) increases in anastomotic Qbr. We conclude that both hypoxemia and hypercarbia increased the anastomotic Qbr through a mechanism involving cyclooxygenase products of arachidonic acid.
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PMID:Hypoxia and hypercarbia increase bronchial blood flow through bronchopulmonary anastomoses in anesthetized dogs. 372 66

The antiaggregation ability of CO2 during ADP- and collagen-induced platelet aggregation has been discovered in cats under hypercapnia. The effect persisted after Pco2 normalization. The inhibition of cyclooxygenase by indomethacin suppressed the antiaggregation activity of CO2 in vivo but not in vitro. While estimating the regulatory role of CO2 in the metabolic control of cerebral circulation, it is also of importance to take into account the antiaggregation ability of CO2.
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PMID:[Effect of CO2 on thrombocyte aggregation in the cat]. 642 43

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

The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF was measured by intracarotid injection of 133Xe. Progressive increases in paCO2 of 10 mmHg, at intervals of about 8-10 minutes, were associated with gradual increases in CBF until a paCO2 level of 115 mmHg was reached. No further CBF changes (from the maximum value of 446 +/- 70 ml 100 g-1 min-1) were seen with additional step increase in paCO2. Intracarotid infusion of 7.5 mg/kg NOLAG significantly attenuated the CO2-elicited CBF increase by about 45-65% at paCO2 values below 115 mmHg. Beyond this level, there was a lesser inhibition of about 27-35%. 30 mg/kg NOLAG had essentially the same effect as 7.5 mg/kg NOLAG. 50 mg/kg NOLAG, given intraperitoneally (i.p.) twice daily for 4 days, also caused an attenuated CBF response to CO2, but the inhibitory effect was significantly less than with acute NOLAG administration in the paCO2 range of 61-90 mmHg. Infusion of L-arginine, 1 g/kg/h, prevented the effect of 7.5 mg/kg NOLAG. Indomethacin, 10 mg/kg, i.v. produced a more dramatic attenuation of the response, to the extent that the steady rising curve of CBF as a function of paCO2 was almost completely abolished. With indomethacin, a moderate increase (50%) in CBF was seen at the lowest level of hypercapnia, but raising paCO2 above this level did not result in further increases in CBF. This effect could not be prevented by L-arginine. When combining 7.5 mg/kg NOLAG with 10 mg/kg indomethacin, the response to hypercapnia was totally blocked. The results suggest that NOLAG and indomethacin act through different mechanisms on the hypercapnic CBF response, and that indomethacin is the more powerful inhibitor.
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PMID:Comparison of the effects of NG-nitro-L-arginine and indomethacin on the hypercapnic cerebral blood flow increase in rats. 801 27

In helical strips of Japanese monkey cerebral arteries contracted with vasoconstrictors, applications of high CO2 (15% compared with 5% CO2 in control media) and hypertonic NaHCO3 (50 mM) produced relaxations. Similar relaxations were also obtained in human cerebral arterial strips. Hypercapnia increased PCO2 and resulted in acidosis in the bathing media, and the addition of NaHCO3 restored the pH to normal with high PCO2 and increased the osmotic pressure. The relaxant responses were not influenced by endothelium denudation and treatment with indomethacin. The hypercapnia-induced relaxation was suppressed by ouabain but was unaffected by amiloride. On the other hand, hypertonic bicarbonate-induced relaxations were inhibited by ouabain as well as by amiloride. Removal of Na+ from the bathing media abolished the hypercapnia-induced relaxation but did not alter the hyperosmolar relaxation. In contrast to hypertonic NaHCO3, isotonic bicarbonate solutions contracted the arterial strips by neutralizing the pH under hypercapnia. It may be concluded that relaxations elicited by hypercapnic acidosis are associated with a fall of extracellular pH and an activation of the electrogenic Na+ pump, and those caused by hyperosmolarity are due to stimulation of the Na(+)-H+ exchange and the Na+ pump. Endothelium-derived vasoactive substances and cyclooxygenase products do not appear to be involved in these relaxations of monkey cerebral arteries under the experimental conditions used.
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PMID:Monkey cerebral arterial relaxation caused by hypercapnic acidosis and hypertonic bicarbonate. 821 29

Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral arterioles. We therefore investigated the effect of indomethacin on the CBF increase caused by acetazolamide (Az), a drug that induces brain extracellular acidosis, which triggers its effect on CBF. We compared the results to the inhibitory effect of indomethacin on the CBF increase during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to block almost completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but it did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO2 reactivity by a nonprostaglandin-mediated mechanism that directly interferes with the regulation of cerebrovascular tone mediated by extracellular pH.
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PMID:Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis: a mechanism for its effect on hypercapnia? 831 25


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