Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

The use of acetazolamide, a carbonic anhydrase inhibitor, in chronic obstructive pulmonary disease (COPD) remains controversial. A substantial improvement in blood gas values has been documented, with correction of metabolic alkalosis in COPD, in hypoxemic sleep apnea at high altitudes and in acute mountain sickness. This randomized, double-blind study examined the short and long term effects of acetazolamide (2 X 250 mg) on 14 patients with hypoxemia, hypercapnia and metabolic alkalosis (paO2 49 +/- 5.2 mm Hg, paCO2 50 +/- 3.6 mm Hg, base excess + 5.7 +/- 2.3). A crossover between acetazolamide and placebo occurred on days 3, 6 and 9. On day 12 the patients were again randomized and one group further treated with acetazolamide for 4 1/2 (1-7) months. During the short term phase, a significant rise in paO2 to 58 +/- 6.6 mm Hg with acetazolamide was noted, followed by a drop to 53 +/- 5.7 mm Hg with placebo. The paO2 of the five patients on long-term acetazolamide therapy remained unchanged (59 +/- 2.5 mm Hg) while the untreated patients showed a significant drop in paO2 to 46 +/- 8.2 mm Hg. No side effects and no severe metabolic acidosis were noted during acute or long term treatment. Acetazolamide appears to improve hypoxemic and hypercapnic COPD patients with metabolic alkalosis on short and long term therapy.
...
PMID:[Acetazolamide in hypercapnic chronic obstructive lung disease--a renaissance?]. 682 42

Testing vasoreactivity with CO2 or Diamox is a common diagnostic procedure for the study of haemodynamics in stroke patients. CO2 reactivity (CO2R) was tested in 5 baboons six hours after permanent occlusion of the left middle cerebral artery (MCA) in order to attain new insights into interpretation of vasoreactivity tests. Using the microsphere method, cerebral blood flow (CBF) was determined in the various vascular territories as well as in the centre of the ischemia, the penumbra and the remaining MCA-tissue. CBF decreased significantly in the affected MCA in all animals and in addition in the contralateral cerebellum in one animal (p < 0.05). In addition, the left anterior cerebral artery (ACA) demonstrated a similar decrease. During hypercapnia CBF increased in all areas with the exception of the left, occluded MCA territory. Thus CO2 enhanced the difference between ischaemic and non-ischaemic tissue (i.e., tissue with diaschisis). Mean CO2 R was 3.37 ml/100 g/min/mmHg in the right MCA, 0.16 in the left. While the left ACA demonstrated a decreased perfusion during normocapnia in a similar range to the MCA territory, only CO2R was able to identify precisely the territory of the occluded vessel. CO2 R was zero or negative in the ischaemic core, close to zero in the penumbra and profoundly decreased in the remaining MCA tissue. The overall CO2 R of the MCA was almost zero, suggesting vasoparalysis in response to hypercapnia in the core and penumbra and exhausted CO2 R even in non-infarcted, non-penumbral tissue. One animal displayed a negative CO2 R equivalent to an intracerebral steal-phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:CO2 reactivity in the ischaemic core, penumbra, and normal tissue 6 hours after acute MCA-occlusion in primates. 812 41

Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p<0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p<0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p<0.01). The net result was a stimulation of ventilation at PET,CO2 <5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.
...
PMID:Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat. 987 70

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.
...
PMID:Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia. 1020 9

Carbonic anhydrase (CA) may modulate regional blood flow by mediating changes in extra- and intracellular pH. We hypothesized that CA inhibition with acetazolamide would inhibit the kinetics and magnitude of hypoxic pulmonary vasoconstriction (HPV). Isolated rabbit lungs were ventilated and perfused in situ at constant flow, with buffer containing red blood cells. Preparations were sequentially challenged with hypoxic (FI(O(2)) 0.05) and/or hypercapnic (FI(CO(2)) 0.10) gas mixtures for 5 or 10 min. In the experimental groups, acetazolamide (33 microM) was added to the perfusate after establishing baseline responses, and gas challenges were repeated; control groups were studied without acetazolamide. Acetazolamide reduced the increase in pulmonary artery pressure (DeltaPAP) and the rate of pressure rise by approximately 30-50% during hypoxia and combined hypoxia/hypercapnia. The reduction in DeltaPAP occurred for both 5 and 10 min challenges. Acetazolamide did not affect expired nitric oxide concentrations. We conclude that acetazolamide reduces both the magnitude and kinetics of HPV by a mechanism that does not involve nitric oxide.
...
PMID:Acetazolamide reduces hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. 1099 92

The rostral fastigial nucleus (FNr) of the cerebellum facilitates the respiratory response to hypercapnia. We hypothesized that some FNr sites are chemosensitive to focal tissue acidosis and contribute, at least partially, to respiratory modulation. Minute ventilation (VE) was recorded in 21 anesthetized and spontaneously breathing rats. Acetazolamide (AZ; 50 microM) was microinjected unilaterally into the FNr while an isocapnic condition was maintained throughout the experiment. AZ (1 or 20 nl) injection into the FNr significantly elevated VE (46.0 +/- 6.7%; P < 0.05), primarily via an increase in tidal volume (31.7 +/- 3.8%; P < 0.05), with little effect on arterial blood pressure. This augmented ventilatory response was initiated at 6.3 +/- 0.8 min and reached the peak at 19.7 +/- 4.1 min after AZ administration. The same dose of AZ delivered into the interposed and lateral cerebellar nuclei, or vehicle injection into the FNr, failed to elicit detectable cardiorespiratory responses. To determine whether the ventilatory response to AZ injection into the FNr resulted from an increase in respiratory central drive, the minute phrenic nerve activity (MPN) was recorded in seven paralyzed and ventilated rats. Similar to VE, MPN was increased by 38.9 +/- 8.9% (P < 0.05) after AZ administration. Our results suggest that elevation of CO2/H+ within the FNr facilitates respiratory output, supporting the presence of ventilatory chemoreception in rat FNr.
...
PMID:Microinjection of acetazolamide into the fastigial nucleus augments respiratory output in the rat. 1164 79

Transcranial Doppler sonography has become widely used in assessing cerebral vasomotor reactivity which provides information regarding cerebral autoregulation and collateral circulation. Cerebral vasomotor reactivity is defined as a shift between cerebral blood flow or cerebral blood velocity before and after administration of a potent vasodilatory stimulus test. Three such tests are currently used for this purpose: the apnea test, CO2 inhalation and the Diamox test (i.v. acetazolamide), all of which are based on the dilatatory response of cerebral blood flow to hypercapnia. Certain advantages of the Diamox test were described, but each of the three tests has its strong and weak points, and this will be the topic under discussion. There are several practical applications of the combined TCD and the vasodilatory tests in assessing of cerebral vasomotor reactivity: 1. To evaluate the intracranial hemodynamic status in patients with carotid occlusive disease with the intent of predicting the occurrence of ischemic brain events. 2. To compare intracranial hemodynamics before and after carotid endarterectomy. 3. To compare autoregulation and collateral circulation in the different parts of the circle of Willis. 4. To predict dementia after stroke. In summary, the potential clinical usefulness of combined TCD and provocative vasodilatory tests has been clearly shown. Further large scale studies are needed in order to augment the applications of cerebral vasomotor reactivity assessment in the clinical setting.
...
PMID:TCD and the Diamox test for testing vasomotor reactivity: clinical significance. 1200 54

Acetazolamide (Acz) is used at altitude to prevent acute mountain sickness, but its effect on exercise capacity under hypoxic conditions is uncertain. Nine healthy men completed this double-blind, randomized, crossover study. All subjects underwent incremental exercise to exhaustion with an inspired O(2) fraction of 0.13, hypoxic ventilatory responses, and hypercapnic ventilatory responses after Acz (500 mg twice daily for 5 doses) and placebo. Maximum power of 203 +/- 38 (SD) W on Acz was less than the placebo value of 225 +/- 40 W (P < 0.01). At peak exercise, arterialized capillary pH was lower and Po(2) higher on Acz (P < 0.01). Ventilation was 118.6 +/- 20.0 l/min at the maximal power on Acz and 102.4 +/- 20.7 l/min at the same power on placebo (P < 0.02), and Borg score for leg fatigue was increased on Acz (P < 0.02), with no difference in Borg score for dyspnea. Hypercapnic ventilatory response on Acz was greater (P < 0.02), whereas hypoxic ventilatory response was unchanged. During hypoxic exercise, Acz reduced exercise capacity associated with increased perception of leg fatigue. Despite increased ventilation, dyspnea was not increased.
...
PMID:Acetazolamide reduces exercise capacity and increases leg fatigue under hypoxic conditions. 1239 Oct 68

Central CO(2) chemoreception and the role of carbonic anhydrase were assessed in brain stems from Rana catesbeiana tadpoles and frogs. Buccal and lung rhythms were recorded from cranial nerve VII and spinal nerve II during normocapnia and hypercapnia before and after treatment with 25 microM acetazolamide. The lung response to acetazolamide mimicked the hypercapnic response in early-stage and midstage metamorphic tadpoles and frogs. In late-stage tadpoles, acetazolamide actually inhibited hypercapnic responses. Acetazolamide and hypercapnia decreased the buccal frequency but had no effect on the buccal duty cycle. Carbonic anhydrase activity was present in the brain stem in every developmental stage. Thus more frequent lung ventilation and concomitantly less frequent buccal ventilation comprised the hypercapnic response, but the response to acetazolamide was not consistent during metamorphosis. Therefore, acetazolamide is not a useful tool for central CO(2) chemoreceptor studies in this species. The reversal of the effect of acetazolamide in late-stage metamorphosis may reflect reorganization of central chemosensory processes during the final transition from aquatic to aerial respiration.
...
PMID:Central CO2 chemoreception in developing bullfrogs: anomalous response to acetazolamide. 1257 Nov 43

Acetazolamide (ACZ), a carbonic anhydrase inhibitor, results in altered neuromuscular function secondary to depressed afferent transmission in intact humans. One effect of ACZ is hypercapnia. Thus, to test if the neuromuscular depression observed following ACZ treatment is related to elevated CO(2), human subjects ( n=10) were exposed to 15 min of room air (0% CO(2)) or hypercapnia (7% inspired CO(2)), and neuromuscular function was evaluated. Isometric force (36.8 to 31.1 N) and peak-to-peak electromyographic amplitude (EMG, 1.5 to 1.0 mV) associated with an Achilles tendon tap, and soleus H(max):M(max) ratio (69.0 to 62.2%) were depressed, while EMG latency (34.8 to 39.8 ms) was increased by hypercapnia. Reflex recovery profiles (following a conditioning tap to the contralateral Achilles tendon), motor nerve conduction velocity, amplitude of the maximum M-wave, and peak twitch tension at M(max) were unaltered by hypercapnia. We conclude that elevated CO(2) impairs neuromuscular function through effects on afferent transmission or synaptic integrity between type Ia fibers of the muscle spindle and the alpha motor neuron, without affecting the muscle spindle, efferent conduction or skeletal muscle force-generating capacity.
...
PMID:Hypercapnic impairment of neuromuscular function is related to afferent depression. 1295 22


<< Previous 1 2 3 Next >>

---