Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Present study is designed to examine an effect of Stobadine, a new cell-protective agent with antiarrhythmic properties, on survival, electron microscopic changes in microvasculatory bed of selected brain areas and acid-base parameters of arterial blood after global brain ischemia and reperfusion. Forty dogs (weighting 6 to 15 kg) were anesthetized using pentobarbital i.v. (5%, 35 mg/kg). An intubation and controlled ventilation was performed. One catheter was placed into v. femoralis (for drug administration), another to a. femoralis (for blood samples) and third one into the left common carotid artery (continuous brain blood feeding pressure measurement). Each dog underwent an surgical obstruction of principal brain-supplying arteries and immediate administration of hypotensive agent (Arfonad, 0.062%) resulting in 7 minutes lasting global brain ischemia (brain feeding pressure 1.0-1.5 kPa). If survived, animals were killed at one (perfusion-fixed for electron microscopy) or three days after ischemia. Ultrastructural changes were evaluated at 24 hour of recirculation (control and S2 groups only). Vehicle or 1, 2 or 5 mg/kg of Stobadine (group S1, S2, S5 resp.) i.v. was given 30 minutes prior to ischemia. Significantly longer survival was observed in group S2 (8 of 11 until 72 hour) as compared to control group (none of 7, p < 0.005 by Student's t-test). The ultrastructural changes of blood-brain barrier structures were none or minimal in S2 (single damage type), but in control group three major types of capillary damages has appeared at 24 hour after insult. They include intravascular coagulopathy (type I), no-reflow (type II) phenomenon with astrocyte edema, and capillary necrosis (type III) finally. Stobadine pretreated animals experienced hypercapnia, elevated arterial O2 and slight deeper acidemia (depending on dosage) as compared to control group. Respiratory compensation of metabolic acidosis was present in control group, but lacking in all stobadine pretreated animals. Stobadine at 2 mg/kg improves survival (Student p < 0.005, Mantel-Cox p < 0.05, Fischer p = 0.004). Stobadine has a protective effect on neurons and structures of blood-brain barrier (endothel, astrocytes, basement membrane) seen in electron microscope.
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PMID:Effects of stobadine on survival, histopathologic outcome and acid-base status after global brain ischemia in dogs. 756 Sep 9

The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBF) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experimental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either L-n-monomethyl arginine or nitro L-arginine. During basal conditions (PaCO2 of 38-42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p<0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between ICA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of L-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF. Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 +/- 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypertension is not mediated by NO; and increasing PaCO2 induces increased NO production.
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PMID:Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates. 861 39