Role of the peripheral chemoreflex in the early stages of ventilatory acclimatization to altitude
Section snippets
The basic observation
Ventilatory acclimatization to altitude/hypoxia (VAH) may be defined as a progressive increase in ventilation () and arterial/alveolar , and fall in arterial/alveolar , that occurs when an individual or animal is exposed to the hypoxia of high altitude. In such a definition, the word “progressive” is key to understanding the phenomenon. Acclimatization does not refer to the acute adjustments that occur in response to the reduction in environmental —these include both the rapid
Does early ventilatory acclimatization to altitude/hypoxia (VAH) first require the development of an associated respiratory alkalosis?
A century ago, Haldane and Priestley (1905) published their seminal paper demonstrating the exquisite sensitivity of the human respiratory system to variations in alveolar , and contrasting this with the system's much lower sensitivity to variations in alveolar . These findings, coupled with the observation that CO2 exerts many of its effects on through pH change, have subsequently had a great influence on the search for an understanding of VAH. In particular, hypotheses have
The speed with which the sensitivity of the acute hypoxic ventilatory response (AHVR) changes during VAH in humans
A major objection that may be lodged in relation to the conclusions of the previous section is that the rapid change in the AHVR that our laboratory observed with sustained hypoxic exposure (Fig. 1) has not been observed in other studies. Sato et al. (1992) reported that AHVR did indeed increase following exposure to altitude, but only after three days of exposure by which time most of the fall in had already occurred (Fig. 2). They concluded, “The HVR [hypoxic ventilatory response] rise
Methodological issues relating to the measurement of AHVR: the importance of CO2
A major methodological difference between the studies reporting an early change in AHVR and those reporting a slower change in AHVR is the level of the background against which the test hypoxic stimulus was presented. In the studies reporting an early change in AHVR, the against which the test hypoxic stimulus was presented was kept constant between tests. In the studies reporting a slower change in AHVR, was adjusted downwards from test to test in order to ensure that the
Direct recordings from the carotid sinus nerve
There are only a few experimental studies in animals where an attempt has been made to record from carotid sinus afferents over an extended period of hypoxia. In anaesthetized cats, Barnard et al. (1987) failed to find any progressive sensitization of the carotid body over a sustained period of 2–3 h of hypoxia. However, they did find sensitization of the carotid body had occurred following a 28-day exposure to hypoxia. Also in anaesthetized cats, Vizek et al. (1987) found that there had been
The effects of hypoxia on gene expression
The idea that the progressive changes involved in VAH could be driven directly by hypoxia (without the need for any mechanism involving slow changes in pH) is further supported by our increased recognition of the importance of hypoxia as a regulator of gene expression (Cummins and Taylor, 2005). In 1992, the first of the hypoxia-inducible factor (HIF) family of transcription factors was identified (Semenza and Wang, 1992). Subsequently, it has been shown to be present in a wide variety of cell
Do changes in acid–base balance have any causal role in generating VAH?
If alterations in gene expression form the principal mechanism underlying VAH, are there any effects associated with acid–base adjustments? In general, it is accepted that any compensatory metabolic acidosis (provoked by the respiratory alkalosis of poikilocapnic exposure to hypoxia) develops much more slowly than the majority of the rise in and fall in associated with VAH (Kellogg, 1963, Severinghaus et al., 1963, Forster et al., 1975). This is in keeping with the experiments
Concluding remarks
This brief review emphasizes that the term VAH encompasses responses to hypoxia that occur over very different timescales—starting within an hour or two of exposure, but not necessarily complete even following an exposure of 1–2 weeks duration. The review describes how different mechanisms are likely to be dominant over different stages of such a timescale. It focuses on the early stages of VAH (∼first 24–48 h in humans) and argues that early VAH does not appear to be driven primarily through
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Altitude training for elite endurance athletes: A review for the travel medicine practitioner
2016, Travel Medicine and Infectious DiseaseCitation Excerpt :Acetylcholine, acting in concert with adenosine triphosphate (ATP), endothelin, and reactive oxygen species, alters afferent discharge from the carotid bodies, and effects a hypoxic ventilatory response (HVR) [9–11]. It has become clear that HIF-mediated changes within glial and neuronal cells in the brainstem also exert an influence on respiratory motor output [9,12]. HVR is critical during exercise at high altitude.
Breathing and sleep at high altitude
2013, Respiratory Physiology and NeurobiologyCitation Excerpt :Many unanswered questions remain. Based on these CSF studies in humans, failure of the CSF theory to adequately explain early VAH led to the idea that early VAH involves an increase in peripheral chemoreceptor activity [reviewed in: (Robbins, 2007)]. Supporting this: (i) carotid body denervation/resection impairs acclimatization in animals (e.g., (Bisgard and Vogel, 1971; Forster et al., 1981, 1976)); (ii) in an isolated carotid body preparation in goats, VAH did not develop after 4 h of systemic hypoxia when their carotid bodies were perfused with a normoxic and normocapnic solution (Weizhen et al., 1992), and (iii) in animal models, carotid body neural activity is increased during the acclimatization process (Nielsen et al., 1988; Vizek et al., 1987).
Duration at high altitude influences the onset of arrhythmogenesis during apnea
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