Increase In Alveolar-arterial Oxygen Gradient Research Articles

Daytime Hypoxemia, Sleep-Disordered Breathing, and Laryngopharyngeal Findings in Multiple System Atrophy

The mechanism underlying nocturnal sudden death in patients with MSA remains unclear. It may be explained by upper airway obstruction, such as vocal cord abductor paralysis; an impairment of the respiratory center, such as Cheyne-Stokes respiration; or an impaired hypoxemic ventilatory response. To investigate the mechanism of sleep-disordered breathing in multiple system atrophy (MSA). We recruited 21 patients with probable MSA who were admitted sequentially to our hospital, and performed daytime blood gas analysis, pulmonary function tests, polysomnography, and fiberoptic laryngoscopy during wakefulness and with the patient under anesthesia. A decrease in arterial oxygen pressure and an increase in alveolar-arterial oxygen gradient significantly correlated with disease duration (P = .045 and .046, respectively). Polysomnography demonstrated Cheyne-Stokes respiration in 3 (15%) of 20 patients. Fiberoptic laryngoscopy during wakefulness showed that 3 (14%) of the 21 patients exhibited vocal cord abductor paralysis, and laryngoscopy under anesthesia showed that 9 (45%) of 20 patients exhibited vocal cord abductor paralysis. Laryngoscopy under anesthesia also revealed that 11 (55%) of 20 patients showed upper airway obstruction in places other than the vocal cords, including obstruction at the base of the tongue or soft palate. In addition, it demonstrated novel laryngopharyngeal findings, such as floppy epiglottis and airway obstruction at the arytenoid. We observed daytime hypoxemia with an increased alveolar-arterial oxygen gradient, Cheyne-Stokes respiration, and novel abnormal laryngopharyngeal movements in patients with MSA. We also found that laryngoscopy under anesthesia might be useful for evaluating upper airway obstruction. The significance of these findings to the mechanism of sudden death in those with MSA needs to be examined.

Differential effects of salmeterol on lung endothelial and epithelial leakage in sheep.

Salmeterol has been shown to prevent the influx of proteins into the air spaces of lungs of guinea pigs given intravenous histamine. To determine whether the salmeterol acts to stabilize the epithelial or endothelial barrier, we ventilated anesthetized sheep with aerosolized salmeterol before infusing histamine intravenously at a rate of 4 micrograms.kg-1.min-1 for 3 h. Changes in endothelial permeability were assessed by measuring the flow of lymph and proteins from the lungs. The influx of proteins into the air spaces was detected by performing single-cycle lavages to measure the concentration of circulating 125I-albumin in the epithelial lining fluid. Intravenous histamine increased the lymph flow to 13.2 +/- 6.8 ml/h compared with the control value of 5.6 +/- 2.8 ml/h (P < 0.05). Histamine also increased the concentration of 125I-albumin in the epithelial lining fluid from 1.8 +/- 0.9 to 8.5 +/- 2.5% of the plasma concentration (P < 0.01) and the postmortem lung water volume from 3.5 +/- 0.5 to 5.0 +/- 0.8 mg/g dry lung wt (P < 0.05). Pretreatment with 2.5 mg of aerosolized salmeterol prevented the influx of proteins into the air spaces and the increase in the postmortem lung water volume but it also increased the lung lymph flow even further to 20.0 +/- 5.6 ml/h (P < 0.05), increased the lymph-to-plasma protein ratio from 0.77 to 0.91, and tripled the increase in alveolar-arterial oxygen gradient caused by histamine alone. Pretreatment with 2.5 mg of intravenous salmeterol had essentially the same effect as salmeterol administered by aerosol. We conclude that salmeterol decreases lung epithelial permeability but increases lung endothelial permeability due to intravenous histamine in sheep.

Arterial Oxygenation during Artificial Ventilation. The Effect of Airway Closure and of Its Prevention by Positive End-Expiratory Pressure

Airway closure and arterial blood gases were measured in 11 healthy subjects both before and during anaesthesia with artificial ventilation, prior to routine surgery. The functional residual capacity was then increased by positive end-expiratory pressure (PEEP), so that ventilation took place at a lung volume where no airway closure was present, and the effect on arterial oxygenation was again investigated. A significant increase in alveolar-arterial oxygen gradient occurred in the group of seven patients in whom airway closure within a tidal breath could be demonstrated during anaesthesia, but there was no significant change in the four patients in whom airway closure could not be demonstrated. There was no improvement in arterial oxygenation on increasing functional residual capacity (FRC) in either group. It may well be that this failure to improve oxygenation was due to a deleterious effect of PEEP on the circulation, even though the PEEP was the minimum required to abolish airway closure.

Arterial Oxygenation During Artificial Ventilation: The Effect of Airway Closure and of its Prevention by Positive End‐Expiratory Pressure

Airway closure and arterial blood gases were measured in 11 healthy subjects both before and during anaesthesia with artificial ventilation, prior to routine surgery. The functional residual capacity was then increased by positive end-expiratory pressure (PEEP), so that ventilation took place at a lung volume where no airway closure was present, and the effect on arterial oxygenation was again investigated. A significant increase in alveolar-arterial oxygen gradient occurred in the group of seven patients in whom airway closure within a tidal breath could be demonstrated during anaesthesia, but there was no significant change in the four patients in whom airway closure could not be demonstrated. There was no improvement in arterial oxygenation on increasing functional residual capacity (FRC) in either group. It may well be that this failure to improve oxygenation was due to a deleterious effect of PEEP on the circulation, even though the PEEP was the minimum required to abolish airway closure.