Reply from P. Haouzi and B. Chenuel
Year: 2006
Type: letter
Abstract: We thank Dr Poon for his interest in our recent paper. In his ‘critique’ he addresses four points, apparently aiming to reconcile the observations reported in our two recent studies with his own view on the control of breathing during exercise (Poon, 1987). It is important to recognize, however, that many of his contentions are based not on actual experimental data such as we reported in our present or previous papers (points 1 and 3 below) nor on other experimental evidence found in the literature (point 4) but rather on his own personal conceptions – many of which, we believe, are not only highly questionable but are not even reasonable (points 1 and 4). 1. From the data available in our previous paper (Haouzi et al. 2003), Poon deduces that the –cP (cephalic P) relationship obtained in our sheep reflects a chemosensitive control system gain as high as 14 l min−1 Torr−1, i.e. able to account for the entire response to contractions on the basis of a 0.8 Torr increase (on average) in cP. While this seems to ‘solve’ the problem of the response to muscle contractions, the argument is entirely specious. Poon's use of ‘gain’ for the –cP relationship when P was increased in the body while it is maintained constant in the carotid circulation is inappropriate. Computing this ratio using the ‘isolated’ head as the frame of reference does not reflect the chemosensitivity of the model during such intervention. It simply shows how much has increased from another source of stimulation (originating in the ‘rest of body’) despite a normal or decreased carotid P. The result is a necessarily infinite, or even negative, –cP slope; this should not be confused with any mysterious change in the gain of the chemosensitivity consistent with some ‘newfound plasticity’. Furthermore, the response to high systemic P was trivially small in almost all instances in all our reports (Haouzi et al. 2003; Haouzi & Chenuel, 2005): the /systemic P ratio ranged from 0.03 to 0.1 l min−1 Torr−1 (see the Result sections). Several mechanisms were put forward in our discussion to account for such change in with high systemic P including the systemic vascular effects of CO2 and the possibility of contamination of the cephalic circulation from the systemic blood. This latter proposal was thought to be highly unlikely, since no trace of technetium injected into the left ventricle was found in the cephalic region. As stated in our previous paper (Haouzi et al. 2003), Fig. 4 is the most extreme example of this type of response. We were so intrigued by this effect that we decided to show it in the paper. Using only this type of response to build a ‘theory’ is unjustified and does not give proper credence to the reality of the data. Indeed, the response to high body CO2 could be virtually absent despite, importantly, a normal ventilatory response to exercise (Haouzi & Chenuel, 2005). What is therefore Poon's rationale for using the –cP ratio obtained during high systemic P (which, as described above, has no physiological meaning) in the interpretation of the response to exercise? Whatever the mechanisms of the residual response to ‘body’ hypercapnia, systemic P is going down by a few Torr during contractions. Even if we assume a small contamination (which will be difficult to explain anatomically), P at the chemoreceptors should, as a result, be if anything slightly lower that the actual value measured in the carotid blood during the contractions. Therefore may we respectfully recommend that Dr Poon reconsider the physiological implications of his computation: a model based on conventional chemosensitivity is unrealistic. In fact, we challenge Dr Poon to find any sheep or human beings with such a chemosensitive gain to experimentally elevated cP. Until then, any of the ‘critiques’ regarding a major change in CO2 chemosensitivity are simply speculative and contradictory to the data provided here and elsewhere. 2. With respect to Dr Poon's concern regarding the possible effects of cutaneous stimulation during electrically induced muscle contractions, we can reassure him that: (a) With the level of anaesthesia we use our animals had no demonstrable cutaneous sensibility. We were unable to trigger any or HR changes (these were continuously recorded throughout the experiment) during nociceptive stimulation of the skin, i.e. cutting the skin or doing more extensive surgery: (b) Electrical stimulation eliciting cutaneous pain causes variations in the timing components of breathing without any effect on tidal volume and trivial change in (Duranti et al. 1991): (c) The response is only dependent on the tension applied on to the muscle and its ensuing metabolic response regardless of the magnitude of the stimulation: (d) The two pairs of large electrodes (10 cm–5 cm, Saint Cloud International Chantonnay, France) are routinely used in patients for rehabilitation. 3. In our sheep model, all the brain structures down to the cervical cord are supplied by the carotid circulation (and not the vertebral system) in which the perfusion pressure and the blood flow are maintained constant by the pump. Consequently, any speculation on putative effect of vertebral flow during the occlusions simply does not apply here (we refer Dr Poon to our Methods section). 4. Finally, Dr Poon's contention that ‘somatic–respiratory coupling mechanism may have more to do with coordination of movements than tracking metabolic rate per se’ is not supported by the temporal profile of the response to contractions of many of muscle endings. It has been consistently demonstrated that the activity of a large population of group III and IV afferent fibres develops progressively during contractions (Mense & Meyer, 1985) with a very long time constant – regardless of the mechanical effects of the contractions (Kaufman et al. 1983). Such a profile is inconsistent with Dr Poon's argument that only movement is monitored. We are pleased to have had the opportunity to respond to the issues raised in Dr Poon's letter. The topic of the control of the exercise hyperpnoea is both important and poorly understood and we, as Dr Poon, continue to accept the challenge of its resolution.
Source: The Journal of Physiology
Authors: Philippe Haouzi, Bruno Chenuel
Institution: Université Henri Poincaré
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2128253467