Blunted hypoxic ventilatory drive in subjects susceptible to high-altitude pulmonary edema

Abstract

It has been proposed that subjects susceptible to high-altitude pulmonary edema (HAPE) show exaggerated hypoxemia with relative hypoventilation during the early period of high-altitude exposure. Some previous studies suggest the relationship between the blunted hypoxic ventilatory response (HVR) and HAPE. To examine whether all the HAPE-susceptible subjects consistently show blunted HVR at low altitude, we evaluated the conventional pulmonary function test, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) in ten lowlanders who had a previous history of HAPE and compared these results with those of eight control lowlanders who had no history of HAPE. HVR was measured by the progressive isocapnic hypoxic method and was evaluated by the slope relating minute ventilation to arterial O2 saturation (delta VE/delta SaO2). HCVR was measured by the rebreathing method of Read. All measurements were done at Matsumoto, Japan (610 m). All the HAPE-susceptible subjects showed normal values in the pulmonary function test. In HCVR, HAPE-susceptible subjects showed relatively lower S value, but there was no significant difference between the two groups (1.74 +/- 1.16 vs. 2.19 +/- 0.4, P = NS). On the other hand, HAPE-susceptible subjects showed significantly lower HVR than control subjects (-0.42 +/- 0.23 vs. -0.87 +/- 0.29, P less than 0.01). These results suggest that HAPE-susceptible subjects more frequently show low HVR at low altitude. However, values for HVR were within the normal range in 2 of 10 HAPE-susceptible subjects. It would seem therefore that low HVR alone need not be a critical factor for HAPE. This could be one of several contributing factors.

Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude

“…In addition, there may be confounding effects of sex and age. Since female subjects were not examined during the same phase of the menstrual cycle, and since there was a higher mean age than in previous studies [8,12,13], it is suggested that these potentially confounding factors [29][30][31] may account, in part, for the negative finding regarding the association between HVR and HAPE susceptibility. From a practical point of view, all those confounders are present in daily practice.…”

“…Most studies report positive associations [8,12,13], although one study found no relationship between HAPE and HVR [14]. Furthermore, some studies have reported associations between susceptibility to HAPE and lower vital capacity [8,9,15,16] or lower functional residual capacity [16].…”

Positive Association of the Endothelial Nitric Oxide Synthase Gene Polymorphisms With High-Altitude Pulmonary Edema

“…1,2,18 The individual susceptibility has been suggested to be associated with enhanced pulmonary vascular responses to hypoxia, hypobaria, and exercise 26 or with blunted hypoxic ventilatory response. 27 Previously, measuring these physiological variables was a traditional means offering some indicators to the susceptibility. 26,27 Such tests, however, lacked sufficient reliability to gain widespread acceptance.…”

“…27 Previously, measuring these physiological variables was a traditional means offering some indicators to the susceptibility. 26,27 Such tests, however, lacked sufficient reliability to gain widespread acceptance. In this study, we used the novel missense variants of the eNOS gene to describe the association of the eNOS gene with HAPE for the first time.…”

High-Altitude Pulmonary Vascular Diseases

“…34 In addition, less hypoxic peripheral chemoreceptor sensitivity may also directly affect the pulmonary vasculature via efferent communication from the brain, since for the same alveolar and arterial PO 2 those with lower HVR have greater HPV. 8 Subjects with lower HVR also have a much lower diuretic response to hypoxia, 35 which may lead to more pulmonary edema than in those that lose more salt and water in the initial several days at high altitude.…”