Changes in Chemoreflex Characteristics Following Acute Carbonic Anhydrase Inhibition in Humans a Rest

Abstract

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (ACZ, 10 mg kg‐1 I.V.) on the peripheral and central chemosensitivity and breathing pattern was investigated in four women and three men aged 25 ± 3 years using a modified version of Read's rebreathing technique. Subjects were exposed to dynamic increases in CO2 in hypoxic and hyperoxic backgrounds during control conditions and following acute CA inhibition. All manoeuvres were repeated twice and averaged for data analysis. The central chemoreflex sensitivities, estimated from the slopes of the ventilatory response to CO2 during hyperoxic rebreathing, increased following acute CA inhibition (control vs. ACZ treatment: 1.87 ± 0.66 vs. 4.07 ± 1.03 l min‐1 (mmHg CO2)‐1, P < 0.05). The increased slope was reflected by an increase in the rate of rise of tidal volume and breathing frequency. Furthermore with ACZ, there was a left‐ward shift of the ventilation vs. end‐tidal PCO2 curve during hyperoxic hypercapnia but not hypoxic hypercapnia. The peripheral chemoreflex sensitivity was isolated by subtracting the hyperoxic slope (central only) from the hypoxic slope (central and peripheral). Following ACZ administration, the peripheral chemosensitivity was blunted (control vs. ACZ treatment: 3.66 ± 0.92 vs. 1.33 ± 0.46 l min‐1 (mmHg CO2)‐1, P < 0.05). In conclusion, acute CA inhibition enhanced the central chemosensitivity to CO2 but diminished the peripheral chemosensitivity.

Acetazolamide

“…However, It is a diuretic that, when given, increases urine bicarbonate excretion, and in doing so, it increases urinary pH. These features can afford some potential clinical benefit for disease states such as metabolic alkalosis, 7,8 nephrolithiasis, 9 rhabdomyolysis, 10,11 contrast-induced nephropathy (CIN), 12 sleep apnea, [13][14][15][16][17][18] and high altitude erythropoiesis. 19,20 In addition, it can be a useful adjunct therapy in patients with diuretic resistance.…”

“…The latter can be a byproduct of the mild metabolic acidosis that occurs with the carbonic anhydrase inhibitor acetazolamide. [13][14][15][16][17][18] This metabolic acidosis stimulates respiratory effort and in doing so, it can remit hypercapnia. In that regard, administration of acetazolamide at night has been shown to decrease the frequency of obstructive events in patients with moderate-to-severe obstructive sleep apnea.…”

The Role of Pharmacological Treatment in the Chemoreflex Modulation

“…This carbonic anhydrase inhibitor leads to mild metabolic acidosis with a consequent: 1) ventilatory compensation (drop in CO 2 arterial levels) and 2) increase in cerebral blood flow. Net effects of these changes are: desensitization of PChS and augmentation of central chemoreflex (the ventilatory response to carbon dioxide) ( Adams and Johnson, 1990 ; Wagenaar et al, 1998 ; Vovk et al, 2000 ; Fontana et al, 2011 ). Moreover, it has been recently demonstrated that administration of acetazolamide diminishes periodic breathing and improves haemoglobin saturation in HF patients ( Fontana et al, 2011 ; Javaheri et al, 2014 ).…”