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

Acetazolamide (Diamox) induced carbonic anhydrase inhibition is an efficient means of eliminating surplus water and bicarbonate in the overhydrated and alkalotic patient. Previous studies have demonstrated an unexpected and unexplained increase in arterial and venous oxygenation during acute carbonic anhydrase inhibition. In the present investigation we assessed the effect of acetazolamide 15 mg kg-1 on pulmonary gas exchange in 10 critically ill, mechanically ventilated patients. Median arterial oxygen tension increased by 0.9 kPa and central venous oxygen tension and content by 16-18% and 6-8% respectively. The improved oxygenation could, however, not be attributed to an improved pulmonary oxygen exchange as both pulmonary venous admixture (Qs Qt-1) and physiological dead space ventilation (VD VT-1) increased. The increase in arterial oxygen tension can be explained by a rightward shift of the oxyhemoglobin dissociation curve due to the increased acidity of the blood during carbonic anhydrase inhibition (Bohr effect). Acetazolamide does not depress oxygen consumption, so the increase in central venous oxygen content probably reflects an improved cardiac performance. This could conceivably be mediated via sympathetic activation in response to acetazolamide induced carbon dioxide retention.
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PMID:Respiratory function and carbonic anhydrase inhibition. 311 60

Prior reports indicate that acetazolamide, an inhibitor of carbonic anhydrase, in moderate doses reduces symptoms of acute mountain sickness, and in large doses increases cerebral blood flow. The effect on flow is not known for a moderate dose, but were flow to increase, then increased cerebral oxygen delivery would be one mechanism of benefit from acetazolamide at high altitude. We utilized Doppler ultrasound in 8 volunteers to determine whether a usual acetazolamide dose (250 mg three times daily) would increase flow velocities in internal carotid and vertebral arteries. Acetazolamide during normoxia decreased pHa, PaCO2, and PETCO2, but baseline flow velocity remained unchanged. In 2 subjects without acetazolamide, voluntary hyperventilation decreased both PETCO2 and flow velocity. Both hypoxia and hypercapnia caused increases in arterial velocities. The increases were not altered by acetazolamide administration. In one subject, 1 g acetazolamide by acute i.v. injection induced an increase in flow velocity (40%) concomitant with a 5 mm Hg decrease in PETCO2, confirming prior reports using similar intravenous dose. In doses employed for prevention of acute mountain sickness, acetazolamide induced metabolic acidosis and may have prevented the fall in velocity usually associated with hypocapnia, but it neither increased baseline cerebral blood flow velocity nor velocity responses to hypoxia and hypercapnia. Benefit of acetazolamide at high altitude may relate to mechanisms other than increased cerebral blood flow.
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PMID:Usual clinical dose of acetazolamide does not alter cerebral blood flow velocity. 340 53

The intrinsic processes involved in the initiation and arrest of seizures are not completely understood. Cortical and cerebellar inhibitory mechanisms, accumulation of metabolic products, and glial uptake of extracellular potassium (K+o), anions, and released neurotransmitters are all important processes that limit focal firing and terminate a seizure once it has been initiated. Of these, the intrinsic cortical inhibitory mechanisms--i.e., recurrent and surround inhibition--appear to be the most important. Active cation and anion transport processes are two metabolic events that have yet to be elucidated but clearly could be involved in terminating a seizure discharge. For example, without an active mechanism to transport chloride, opening of the chloride channel by the inhibitory transmitter GABA would not result in increased chloride permeability. The transient hypoxia and hypercapnia and lactic acidosis that follows a severe tonic-clonic seizure produces a mixed systemic metabolic and respiratory acidosis. In experimental animals, the hypercapnia that results is sufficient to block seizure discharges. Increasing the CO2 concentration significantly reduces the extension to flexion (E/F) ratio of mice given maximal electroshock seizures (MES) and increases the time required for 50% of the animals to recover sufficiently from a first MES to be able to have another MES. The decreased E/F ratio and the increased recovery time (RT50) are both indicative of a decrease in seizure activity. Since the extent to which CO2 is allowed to accumulate in the brain is regulated by the glial specific enzyme carbonic anhydrase (CA), it follows that the glial cell has an integral role in the mechanisms involved in arresting seizure activity. In contrast, hypoxia increased the E/F ratio and decreased the RT50, evidence that seizure activity was enhanced. Another metabolic factor affecting duration of seizure activity, susceptibility to seizures, and recovery from seizures is glucose. Recovery from seizures depends in part on an adequate supply of this energy source. An inverse correlation (R = 0.95) between RT50 and blood sugar was found when the blood sugar was altered experimentally by treatments that altered the endocrine status (pancreatectomy, treatment with alloxan, cortisol, insulin, glucagon, and dextrose). Since glial cells contain (as glycogen) the small amount of glucose present in the brain, they probably hasten the ability of the brain to recover normal function following a seizure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of glial cation and anion transport mechanisms in etiology and arrest of seizures. 370 23

It is well known that carbonic anhydrase plays an important role in the physiological responses of carotid-body chemoreceptors to hypercapnia. Nevertheless the precise location of the enzyme within the carotid body has been a matter of controversy for many years. Using the Hansson method we found histochemical evidence that this enzyme is localized in type I cells. Type II cells and nerve terminals did not show enzymatic activity. These results allow us to define the carotid body as a secondary receptor in the context of the "acidic hypothesis" of transduction in the carotid body.
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PMID:Carbonic anhydrase in the carotid body and the carotid sinus nerve. 392 38

Disorders of systemic acid-base balance have recently been shown to markedly alter intestinal electrolyte transport. These studies were based on earlier acid balance studies in humans and animals, data suggesting the presence of intestinal mucosal Na+-H+ and Cl-HCO-3 exchange processes and the reported effects of acid-base variables on other epithelia. In vivo studies have shown that intestinal net sodium and chloride absorption is markedly affected by systemic pH and carbon dioxide tension (Pco2). Specifically, systemic acidemia (in the rat ileum) and hypercapnia (in the rat colon) increase sodium and chloride absorption, while alkalemia and hypocapnia decrease absorption. In addition, net bicarbonate secretion (in both segments) varies directly with the plasma HCO3 concentration. The rabbit ileum has been studied both in vivo and in vitro and is affected in a similar way. The rat jejunum and rabbit distal colon and gallbladder do not respond to changes in blood pH and Pco2, consistent with the apparent absence of a mucosal Na+-H+ exchange process in these segments. Evidence suggests important roles for cellular carbonic anhydrase activity and the intracellular concentrations of hydrogen, bicarbonate, and calcium ions and calcium-calmodulin in mediating or modulating the effects of the systemic acid-base disorders. In addition, systemic pH may alter the effects of the neural and humoral mediators of intestinal transport.
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PMID:Systemic acid-base disorders and intestinal electrolyte transport. 633 Nov 93

Acetazolamide, an inhibitor of carbonic anhydrase, which catalyzes hydration/dehydration of carbon dioxide, has been used for correction of metabolic alkalosis in patients with chronic obstructive pulmonary disease (COPD). Animal experiments have shown that the gradient between tissue and the alveolar CO2 tension increases after inhibition of carbonic anhydrase, suggesting retention of CO2. In order to determine the true degree of carbon dioxide retention after total inhibition of carbonic anhydrase, 10 patients with COPD and pronounced metabolic alkalosis (base excess above 6) under controlled mechanical ventilation were studied. The study showed that there was a statistically significant increase in tissue PCO2 and a temporary decrease in pulmonary carbon dioxide excretion. Furthermore, it was found that PaO2 and PVO2 increased significantly after inhibition of carbonic anhydrase, which could, at least partly, explain the improvement seen in patients with COPD and metabolic alkalosis after treatment with acetazolamide.
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PMID:Carbon dioxide elimination after acetazolamide in patients with chronic obstructive pulmonary disease and metabolic alkalosis. 641 Jun 68

Carotid body chemoreceptor responses to sudden changes in pETCO2 (end-tidal tracheal CO2 partial pressure) and paCO2 (arterial CO2 partial pressure) from one stable state to another at a constant level of PETO2 (end-tidal tracheal O2 partial pressure) and paO2 (arterial O2 partial pressure) were studied in 18 anesthetized cats. Chemoreceptor activity was recorded from single or pauci-fiber filaments of a cut sinus nerve. During a hypercapnic stimulus by CO2 inhalation the discharge rate rapidly increased to a peak and then adapted to a lower level in 20-30 s showing an overshoot in the response. Likewise, withdrawal of the hypercapnic stimulus was followed by an undershoot in chemoreceptor activity. Hypoxia decreased the latency of the response and increased the overshoot and stable state responses to hypercapnia. The responses to step paCO2 increases by blood perfusion were qualitatively similar but the latency and time to peak amplitude were shorter and the peak amplitude was larger at any given perfusate pO2. The stable state responses to a given paCO2 achieved by CO2 inhalation or by blood perfusion were similar. The transient overshoot and undershoot in the activity produced by the increase and decrease in paCO2 were blocked by acetazolamide, a carbonic anhydrase inhibitor. The results are best explained by postulating that in the carotid body tissue, H+ is generated from CO2 in one compartment in the presence of carbonic anhydrase and is transported to another containing the receptor site in a pO2 dependent way--a high pO2 attenuating and a low pO2 augmenting it.
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PMID:Adaptive response of carotid body chemoreceptors to CO2. 680 May 65

In patients with metabolic alkalosis, compensatory alveolar hypoventilation may induce hypercapnia and hypoxemia. In edematous or normally-hydrated patients without electrolyte deficiencies, acetazolamide--a carbonic anhydrase inhibitor--has been advocated to correct the primary acid-base disturbance, thereby preventing hypoxemia. The hemodynamic consequences and the effect on oxyhemoglobin dissociation of acetazolamide, were studied. Twelve critically ill patients with metabolic alkalosis were given 15 mg/kg body wt. acetazolamide intravenously. Cardiovascular performance was completely unchanged. The P50 was 26.6 mm Hg at the beginning and the end of the study, indicating that hemoglobin-oxygen affinity is unaffected by acetazolamide. In six patients, investigated after open-heart surgery, the arterial oxygen tension increased by 10-45%. This was probably related to the combined effects of slight reductions in total body oxygen consumption or shunting of venous blood through the lungs. Eight of the 12 patients were on controlled ventilation. After acetazolamide there was a mean increase in mixed venous carbon dioxide tension (PvCO2) of 4.5 mm Hg, with no increase in arterial carbon dioxide tension (PaCO2), indicating only a limited interference with carbon dioxide uptake and release of the carbonic anhydrase inhibition. No other adverse reactions were observed.
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PMID:Cardiovascular performance and oxyhemoglobin dissociation after acetazolamide in metabolic alkalosis. 681 46

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.
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PMID:[Acetazolamide in hypercapnic chronic obstructive lung disease--a renaissance?]. 682 42

The effects of intravenous injections of isoproterenol (0.5-2 microgram) on the responses of carotid body chemoreceptor afferents and on integrated phrenic activity were investigated in twelve anesthetized and three decerebrate, unanesthetized cats. All animals were paralyzed and artificially ventilated. Isoproterenol stimulated carotid chemoreceptor activity and this stimulation was augmented by both hypoxia and hypercapnia. Following an injection of isoproterenol, the ratio of the minute phrenic activity relative to mean carotid chemoreceptor activity was increased. Thus, the stimulation of inspiratory phrenic output exceeded the stimulation of the chemoreceptor afferent input, and the peripheral chemoreflex activity does not account for the entire ventilatory response. To distinguish between a direct effect of isoproterenol and a possible secondary effect mediated via an increased venous return and an increased PaCO2, the latencies of the response of carotid chemoreceptors to both isoproterenol and hypercapnia were compared before and after carbonic anhydrase inhibition by acetazolamide. After acetazolamide, the latency of the response to hypercapnia increased from 3.5 sec to 8 sec whereas the latency of response to isoproterenol increased less, from 4.7 sec to 6.3 sec. Thus, isoproterenol stimulation was not mediated by CO2-H+. Propanolol, which blocked the systemic vascular effect, only partially blocked the chemoreceptor stimulation caused by isoproterenol, indicting that the effect of isoproterenol on chemoreceptor activity was not due to systemic cardiovascular changes.
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PMID:Augmentation of carotid body chemoreceptor responses by isoproterenol in the cat. 726 23


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