Accelerated ethanol elimination via the lungs

Ethanol poisoning is endemic the world over. Morbidity and mortality depend on blood ethanol levels which in turn depend on the balance between its rates of absorption and clearance. Clearance of ethanol is mostly at a constant rate via enzymatic metabolism. We hypothesized that isocapnic hyperpnea (IH), previously shown to be effective in acceleration of clearance of vapour anesthetics and carbon monoxide, would also accelerate the clearance of ethanol. In this proof-of-concept pilot study, five healthy male subjects were brought to a mildly elevated blood ethanol concentration (~ 0.1%) and ethanol clearance monitored during normal ventilation and IH on different days. IH increased elimination rate of ethanol in proportion to blood levels, increasing the elimination rate more than three-fold. Increased veno-arterial ethanol concentration differences during IH verified the efficacy of ethanol clearance via the lung. These data indicate that IH is a nonpharmacologic means to accelerate the elimination of ethanol by superimposing first order elimination kinetics on underlying zero order liver metabolism. Such kinetics may prove useful in treating acute severe ethanol intoxication.

Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise

Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PetCO2); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PetCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia [end-tidal Po2 (PetO2) = 300 mmHg] would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extracranial) measurements were measured during exercise [20, 40, 60, and 80% of maximum workload (Wmax)] and during rest while ventilation (V̇e) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇e was uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇e was increased to prevent PetCO2 from rising above resting values (∼40 mmHg). Although PetCO2 differed by 2 ± 3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (∼12-15%) and extracranial (15–20%) blood flow were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extracranial blood-flow (∼17–29%) were greater compared with poikilocapnic normoxia (∼8–20%) at intensities >40% Wmax ( P < 0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extracranial blood-flow differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PetCO2 on CBF during exercise influenced by the prevailing PetO2.

Desensitization of the cough reflex by exercise and voluntary isocapnic hyperpnea

Little is known about the effects of exercise on the sensory and cognitive aspects of coughing evoked by inhalation of tussigenic agents. The threshold for the cough reflex induced by inhalation of increasing nebulizer outputs of ultrasonically nebulized distilled water (fog), an index of cough reflex sensitivity, was assessed in twelve healthy humans in control conditions, during exercise and during voluntary isocapnic hyperpnea (VIH) at the same ventilatory level as the exercise. The intensity of the urge to cough (UTC), a cognitive component of coughing, was recorded throughout the trials on a linear scale. The relationships between inhaled fog nebulizer outputs and the correspondingly evoked UTC values, an index of the perceptual magnitude of the UTC sensitivity, were also calculated. Cough appearance was always assessed audiovisually. At an exercise level of 80% of anaerobic threshold, the median cough threshold was increased from a control value of 0.73 to 2.22 ml/min ( P < 0.01), i.e., cough sensitivity was downregulated. With VIH, the threshold increased from 0.73 to 2.22 ml/min ( P < 0.01), a similar downregulation. With exercise and VIH compared with control, mean UTC values at cough threshold were unchanged, i.e., control, 3.83 cm; exercise, 3.12 cm; VIH, 4.08 cm. The relationship of the fog nebulizer output/UTC value was linear in control conditions and logarithmic during both exercise and VIH. The perception of the magnitude of the UTC seems to be influenced by signals or sensations arising from exercising limb and thoracic muscles and/or by higher nervous (cortical) mechanisms. The results indicate that the adjustments brought into action by exercise-induced or voluntary hyperpnea exert inhibitory influences on the sensory and cognitive components of fog-induced cough.

Neural correlates of voluntary breathing in humans

To investigate the functional neuroanatomy of voluntary respiratory control, blood O2 level-dependent functional magnetic resonance imaging was performed in six healthy right-handed individuals during voluntary hyperpnea. Functional images of the whole brain were acquired during 30-s periods of spontaneous breathing alternated with 30-s periods of isocapnic hyperpnea [spontaneous vs. voluntary: tidal volume = 0.5 ± 0.01 vs. 1.3 ± 0.1 (SE) liters and breath duration = 4.0 ± 0.4 vs. 3.2 ± 0.4 (SE) s]. For the group, voluntary hyperpnea was associated with significant ( P < 0.05, corrected for multiple comparisons) neural activity bilaterally in the primary sensory and motor cortices, supplementary motor area, cerebellum, thalamus, caudate nucleus, and globus pallidum. Significant increases in activity were also identified in the medulla (corrected for multiple comparisons on the basis of a small volume correction for a priori region of interest) in a superior dorsal position ( P = 0.012). Activity within the medulla suggests that the brain stem respiratory centers may have a role in mediating the voluntary control of breathing in humans.