Hypoxic ventilatory response

Alexander CM, Gross JB. Sedative doses of midazolam depress hypoxic ventilatory responses in humans. Anesth Analg 1988 67(4) 377-82. 

The effect of oral tramadol on the ventilatory response to acute isocapnic hypoxia has been studied in 20 healthy volunteers. Tramadol had a small but significant depressive effect on the hypercapnic ventilatory response but no effect on the hypoxic ventilatory response (36). This is in contrast to morphine, which causes 50-60% suppression of the hypoxic ventilatory response. 

Pialoux V, Hanly PJ, Foster GE, et al. Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans. Am /Respir Crit Care Med. 2009 180(10) 1002-1009. 

Both NO and CO may affect (and be involved in) oxygen-dependent phenomena. Accordingly, in vitro experiments have demonstrated that elevated levels of NO or CO can diminish effects of hypoxia on gene transcription. These molecules both activated the internal oxygen-dependent degradation domain and repressed the C-terminal transactivation domain of HIF resulting in less HIF-la that can bind to DNA (Huang et al., 1999). On the other hand, in vivo experiments have demonstrated that NO is one of the modulators of the hypoxic ventilatory response mediated by the rostral mediolateral medulla (de Paula and Branco, 2003). It is not clear at present, whether different cell types respond in a different manner. 

Hoop B, Beagle JL, Maher TJ, Kazemi H. 1999. Brainstem amino acid neurotransmitters and hypoxic ventilatory response. Resp Physiol 118 117-1129. 

Roux JC, Pequignot JM, Dumas S, Pascual O, Ghilini G, et al. 2000. O2-sensing after carotid chemodenervation Hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells. Eur J Neurosci 12 3181-3190. 

Yamamoto M, Nishimura M, Kobayashi S, AMyama Y, Miyamoto K, Kawakami Y. Role of endogenous adenosine in hypoxic ventilatory response in humans a smdy with dipyridamole. J Appl Physiol 1994 76(l) 196-203. 

The fetus is living at low PO2 Mount Everest in utero and is at birth suddenly exposed to high PO2. This transition requires a change of setting of oxygen sensitivity. The carotid and aortic bodies are the main peripheral O2 sensors. While the carotid bodies seem to be the main peripheral chemoreceptors involved in respiratory control, the aortic bodies are more involved in cardiovascular homeostasis in the fetus (1). They have a low hypoxic sensitivity and their involvement in the hypoxic ventilatory response is controversial (2). 

Newborn animals exhibit a typical biphasic response to acute hypoxia with an increase of the basal ventilation at the first minute of exposure, immediately followed by a decrease around the basal level (14,47-52). The secondary phase with a decrease of ventilation is rather due to a central inhibition than to a decrease of peripheral chemoreceptor activity (48,52-58). Similarly, 1-day-old pups first increase and then decrease their ventilation when exposed to 12% O2 (47,59). Moreover, the hypoxic ventilatory response is irregular in the newborn. As the pups grow older, their response to hypoxia develops to a more elaborate response to a second hypoxic challenge. In the adult, the ventilatory response to hypoxia is still biphasic, illustrating the persistence of central inhibition (60). 

Fetal rats that are exposed to prenatal hypoxia during the entire gestation exhibit a significant increase in resting minute ventilation after birth (93-95). However, the hypoxic ventilatory response was not affected by prenatal hypoxia in 1-week-old rats although the subsequent fall leading to the classic biphasic response was aboUshed (95). The dopamine content (95) and the catecholamine synthesis activity (JC Roux, unpublished data) in the CB of prenatal hypoxic pups were reduced compared to the nonexposed control animals. 

Bissonnette JM, Knopp SJ. Developmental changes in the hypoxic ventilatory response in C57BL/6 mice. Respir Physiol 2001 128 179-186. 

Ling L, Olson EB, Vidruk EH, Mitchell GS. Developmental plasticity of the hypoxic ventilatory response. Respir Physiol 1997 110(2-3) 261-268. 

The functional changes within the carotid bodies are tightly connected to the anatomical and neurochemical changes occurring imder chronic hypoxia. If some results show decreased carotid body hypoxic sensitivity after chronic hypoxia (22), it is now well established that successful ventilatory acclimatization relies on an increased sensitivity of carotid body chemoreceptors. Actually, numerous experimental approaches, ranging from hypoxic ventilatory response in awake animals (10,23) to in vitro measurements of ion channel function on glomic cells (24), are consistent with increased carotid body sensitivity following chronic hypoxia. 

A proper acclimatization to hypoxia is very important and determines the overall ability to cope with hypoxia. In climbers at very high altitude, the maximum altitude that an individual can reach is clearly related to the hypoxic ventilatory response measured at sea level and to the extent of the ventilatory acclimatization during ascension (46,46a). At lower altitude, a proper ventilatory acclimatization is also a determinant mechanism for the overall hypoxic acclimatization. Our own observations (unpublished) in rats permanently living at 3600 m above sea level (Bolivian Institute for Altitude Biology—IBBA, La Paz, Bolivia) revealed that following surgical chemodenervation, the hematocrit rose from a baseline level of around 50% to more than 70% within a few weeks and numerous animals died during this period. 

Joseph Y, Dahnaz Y, Cottet-Emard JM, Pequignot JM. Dexamethasone s influence on tyrosine hydroxylase activity in the chemoreflex pathway and on the hypoxic ventilatory response. Pfliigers Arch 1998 435 834—839. 

Schoene RB, Lahiri S, Hackett PH, Peters RM, Jr., Milledge JS, Pizzo CJ, Samquist FH, Boyer SJ, Graber DJ, Maret KH, West JB. Relationship of hypoxic ventilatory response to exercise performance on Moimt Everest. J Appl Physiol 1984 56 1478-1483. 

Herman JK, O Halloran KD, Mitchell GS, Bisgard GE. Methysergide augments the acute, but not the sustained, hypoxic ventilatory response in goats. Respir Physiol 1999 118 25-37. 

Aaron EA, Powell FL. Effect of chroitic hypoxia on hypoxic ventilatory response in awake rats. J Appl Physiol 1993 74 1635-1640. 

In mammals the carotid bodies are situated at the bifurcations of the cormnon carotid arteries into their internal and external branches and are irmervated by the sinus nerve, a branch of cranial nerve EX (Fig. 1). The aortic bodies in mammals, on the other hand, are located in the region of the aortic arch and the roots of the major arteries of the thorax. Their afferent fibers nm in the aortic nerve, a branch of the vagus (Fig. 1). They appear to make little contribution to the resting ventilatory drive in eucapnic normoxia and may not contribute to the hypoxic ventilatory response in many species. It would appear that they participate almost exclusively in cardiovascular reflexes in this group (see Ref. 25 for review). Glomus tissue that may... 

The relationship between ventilation and arterial P02 is relatively flat over the physiological range but substantial increases in ventilation do occur as hypoxia becomes more severe. The amount of variability in this response fi om species to species, however, is enormous. Much of this variabdity undoubtedly reflects adaptation to differing environmental, behavioral, or physiological demands. Thus the blunted hypoxic ventilatory responses seen in fossorial (burrowing) birds and mammals (7,8) are beheved to be an adaptation that minimizes the use of increased... 

Boggs DF, Birchard GF. Relationship between hypoxic ventilatory response and hemoglobin 02-affinity in birds. Physiologist 1982 25 325-325. 

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