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

The effect of oxygen saturation and PCO2 on brain uptake of glucose analogues was studied in rabbits. Using a modified Oldendorf technique, 14C-labeled glucose analogues with a 3H2O reference standard were introduced into the cerebral circulation via the common carotid artery, and the radioactivity of the ipsilateral cerebral cortex was counted and expressed in terms of a brain uptake index (BUI). Severe hypoxia (oxygen saturation less than or equal to 18%) resulted in approximately a 40% decrease in the BUI of 2-deoxy-D-glucose and a 45% decrease in the BUI of 3-0-methyl-D-glucose. Severe hypercapnia (PCO2 = 100 mm Hg) caused a 45% decrease in the BUI of both of these glucose analogues. Hypercapnia superimposed on severe hypoxia had no additional effect. Hypocapnia (PCO2 = 15 mm Hg) increased the BUI of 3-0-methyl-D-glucose by 35% of the control value, and this increase was extremely sensitive to competitive inhibition. When BUI values were plotted against pH rather than PCO2 for the same experiments, there was a good correlation with the calculated linear regression. These results are compared with previous findings on pathologically induced changes in brain uptake of glucose analogues, and the possible role of blood flow is considered in detail.
 ...
PMID:Effects of oxygen saturation and pCO2 on brain uptake of glucose analogues in rabbits. 0 Aug 21

An isolated perfused lung (IPL) preparation was used to investigate the influence of acute environmental stress on lung substrate metabolism. The IPL apparatus consists of four perfusion flasks housed in a temperature-controlled Lucite box with a circulation fan. Lungs are ventilated by a positive pressure ventilation pump. The ventilation is arranged so that the lung can be ventilated with any desired gas composition with concomitant collection of expired gases. The perfusion medium is circulated at 10 ml/min with a peristaltic blood pump, and passes through a specially designed chamber to dampen pulmonary pressure and remove emboli. The perfusion medium presently used in our experiments consisted of washed bovine red blood cells resuspended to a 15% hematocrit with Krebs-Henseleit bicarbonate buffer containing 6% dialyzed Pentex bovine serum albumin. Circulating substrates include 6muM glucose and 0.4muM palmitate. The pH is adjusted to 7.4 with 0.8M Na carbonate. Lungs perfused for 1.5 hr with this apparatus maintain viability, show little edema, maintain blood gases, and show linear incorporation of labeled glucose into lung lipids. Perfused lungs made hypocapnic show a significant (p less than 0.05) rise in lactate and pyruvate, while perfused lungs made hypercapnia show a significant decrease in pyruvate with no change in lactate.
 ...
PMID:Perfused lung preparation for studying altered gaseous environments. 1 88

Thirty monkeys were exposed to controlled systemic hypotension of different magnitudes and duration to determine factors leading to brain injury or cardiovascular failure. Fourteen monkeys developed brain injury. Of these, 6 survived indifinitely and 8 were sacrificed or died within 12-62 hours due to neurologic deterioration accompanied by respiratory failure. Sixteen animals did not develop brain injury, but 9 of these died within 24 hours from documented cardiovascular failure with the remaining 7 survived indefinitely. A highly reproducible threshold for the development of brain injury was found at a mean arterial blood pressure (MABP) of 25 mm Hg. Maintenance MABP was less than or equal to 25 mm Hg in 13 of 14 lesioned monkeys and greater than 25 mm Hg in 15 of 16 non-lesioned monkeys. Maintenance MABP averaged 20.1 +/- 1.1 mm /g in lesioned and 32.1 +/- 1.7 mm Hg in non-lesioned animals (p less than 0.001). Among the non-lesioned animals, death from delayed cardiovascular failure ensued when MABP was maintained between 27 and 35 mm Hg for 90 min or longer. Animals exposed to this range of hypotension for less than 90 min or to MABP exceeding 35 mm Hg for as long as 3 h survived intact. EEG changes occurring during hypotension most accurately predicted neurologic outcome. The threshold MABP required to produce cerebral electric silence was 21-22 mm Hg. Monkeys developing marked brain injury had greater than 25 minutes of EEG flattening, while slightly injured animals had it for 5-15 minutes and those without injury for less than 5 min. Changes in acid-base state, common carotid artery blood flow, and cerebral uptake of glucose and oxygen during hypotension also correlated with neurologic and cardiovascular outcome. Hypoxemia and hypercarbia were not contributory factors in the production of brain injury in this study.
 ...
PMID:Neurologic and cardiovascular effects of hypotension in the monkey. 3 62

The metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
 ...
PMID:A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism. 4 Jun 77

The effect of electrically induced seizures on the permeability of the rat blood-brain barrier was investigated. The small radioactive tracers sodium (24Na+), chloride (36Cl-) carbon labelled thiourea (14C-thiourea) and glucose (14C-D-glucose) were studied in indicator dilution experiments with indium labelled diethylenetriaminepenta-acetic acid (113mIn-DTPA) as reference substance. This method allows a quantitative estimate of the transcapillary loss of solutes, the extraction (E), during a single passage through the brain. Passage of macromolecules was studied using as marker substance Evans Blue which binds to plasma albumin. In the resting state ENa, ECl, Ethiourea and Eglucose were 2.9, 4.8, 9.3 and 12.5%, respectively. During seizures and during shortlasting hypercapnia E glucose decreased while E for the other tracers was unchanged. As cerebral blood flow increased, there must be an increased transfer of test substances into the brain. This finding is in agreement with recent human studies [15]. When Evans Blue was injected intravenously prior to electroshock, there was no staining of brain tissue after one electroshock but following repeated electroshocks some staining was observed. In an attempt quantify this transcapillary loss of albumin by means of indicator dilution, 51Cr-labelled erythrocytes were used as intravascular reference substance against 113mIn-DTPA (a plasma tracer). However, the albumin loss (by pinocytosis or otherwise) occurring after ten electroshocks could not be detected during a single passage through the brain.
 ...
PMID:Blood-brain barrier during electroshock seizures in the rat. 40 65

The effects of stimulation and blockade of dopaminergic receptors on cerebral blood flow and metabolism were investigated in 15 anesthetized baboons. The intravenous administration of apomorphine resulted in immediate, dose-dependent increases in cerebral blood flow (increased by 58% following 0.1 mg/kg apomorphine) which were always accompanied by increases in cerebral oxygen consumption (increased by 36% with 0.1 mg/kg) and glucose uptake (increased by 72% with 0.1 mg/kg). It is suggested that the primary action of apomorphine is on cerebral metabolism and secondarily on cerebral blood flow rather than directly on cerebral vascular smooth muscle. Pimozide, at doses that totally blocked apomorphine-induced increases, was without effect on cerebral blood flow and metabolism. The dilatatory response of the cerebral circulation to hypercapnia was preserved during dopamine-receptor blockade. The basal level of overall cerebral metabolism and hemispheric cerebral blood flow does not appear to be dependent to any large extent on the activity of the dopaminergic pathways in the central nervous system.
 ...
PMID:Cerebral circulation: effect of stimulation and blockade of dopamine receptors. 40 6

The effect of ventilation hypercapnia on pulmonary circulation in man was investigated through separate studies. In the first study on 44 patients with little or no airway obstruction and 20 normal men, 5% CO2 breathing produced (a) significant rise in pulmonary artery pressure (PAP), (b) no significant change in cardiac output, (c) rise in pulmonary vascular resistance, (d) rise in brachial artery pressure (BAP) and (e) no change in wedge pressure (WP). The rise in PAP was more pronounced after 2 min of 10% CO2 breathing in 12 bronchitics. The scond study was carried out in 39 bronchitics and 22 normals while breathing 10% CO2 for 1 min and showed that pulmonary vascular response was independent of systemic vascular response, in that BAP rose later and came back earlier to original level during CO2 breathing. In the third study on 26 severe bronchitics and 15 normals the observed rise in PAP during 10% CO2 breathing was independent of H-ion concentration in the blood since PAP continued to rise even when pH was maintained at air breathing level by intravenous injection of 130 mEq of sodium bicarbonate in 250 cm3 of 5% glucose solution. This study also confirmed the findings in the first study that there was minimal rise in cardiac output, no rise in WP, while PAP and pulmonary vascular resistance rose significantly during ventilation hypercapnia. The responses were pronounced compared with those observed in the first study with 5% CO2. It is postulated that the responses might be due to direct action of CO2 on muscular pulmonary arteries.
 ...
PMID:Pulmonary vascular response to ventilation hypercapnia in man. 77 60

The aim of this paper has been to review and discuss the past and the recent investigations concerned with the study of cerebral transport phenomena in pathological conditions which have been divided into two main parts: (1) the effects of experimentally induced blood brain barrier (BBB) injury by (a) HgCl2 or (b) hyper-osmolar intracarotic perfusate; and (2) the effects of ischemia or of an altered oxygen saturation and pCO2 tension on glucose and/or amino acids and/or protein transport across the BBB, in the syanptosomes and cerebral capillaries. The most important observations were as follows: (1) HgCl2 or hyperosmolar perfusates produced an increased BBB permeability to protein tracers but the brain uptake of glucose analogues was found decreased following the former, and increased (except for lactamide) after the latter treatment. (2) (a) In ischemia, the noted increased vesicular transport of peroxidase, as well as the increased saturable and non-saturable passage of glucose analogues across the BBB depended on the duration of cerebral deprivation of blood supply which never resulted in degeneration of endothelial cells of the brain vessels. (b) The progressively decreased specific 2-deoxy-D-glucose uptake in the synaptosomes seen during cerebral ischemia of 30-180 minutes returned to the level of controls 1 hour after reestablishment of cerebral circulation. (c) A decrease in brain uptake of glucose analogues and amino acids (with few exceptions) was observed in severe hypoxia and hypercapnia while an increase or no change in the brain uptakes was seen in hypocapnia. (d) Preliminary investigations of the 2-DG uptake by the cerebral capillaries obtained by fractionation of the brain from animals subjected to normal or altered oxygen saturation and pCO2 tension suggested that cerebral glucose uptake may be directly related to its capillary function.
 ...
PMID:Pathological aspects of brain transport phenomena. 78 95

The influence of brain norepinephrine on cerebral metabolism and blood flow was examined because exogenous norepinephrine, administered in a way that the blood-brain barrier is bypassed, has been shown to effect pronounced changes in the cerebral circulation. Reserpine (40 mug/kg, by intracarotid infusion) was administered in order to release brain norepinephrine in five anesthetized baboons. Reserpine significantly increased cerebral oxygen consumption (23%) and cerebral blood flow (50%). This response lasted for approximately 60 min. In a further five animals, effects of central beta-adrenoreceptor blockade were studied. Pro pranolol (12 mug/kg-min) produced an immediate, significant reduction in both cerebral oxygen consumption (40%) and cerebral glucose uptake (39%). Cerebral blood flow was reduced minimally. However, the responsiveness of the cerebral circulation to induced hypercapnia was severely attenuated from a gradient of 3.22 before, to 1,11 after, administration. These experiments suggest that central norepinephrine can influence the cerebral circulation primarily through noradrenergic effects on brain metabolism.
 ...
PMID:Influence of endogenous norepinephrine on cerebral blood flow and metabolism. 96 2

Total cerebral blood flow and oxidative cerebral metabolism were measured at normal pCO2, hypocapnia and hypercapnia in 15 unconscious patients in the acute phase after head trauma. In the basal position (normal CO2) measurements were within normal limits and did not correspond to the severity of the clinical picture. But on altering arterial pCO2 there were market changes in oxidative cerebral metabolism, which suggests an abnormal cerebral regulatory mechanism. Measurement of the same functions 14 days later indicated, on the one hand, persistence of changes, but, on the other, a return to normal of previously markedly elevated cerebral glucose uptake. Comparing cerebral blood flow and metabolism between patients who survived and those who died in the acute phase after brain damage, there were no significant differences.
 ...
PMID:[Changes in cerebral blood flow and oxidative cerebral metabolism after extensive acute head trauma (author's transl)]. 112 47


1 2 3 4 5 6 7 8 9 10 Next >>