Abstract
We investigated the interaction between hypoxia and hypercapnia on ventilation and on cerebro-cardio-vascular control. A group of 12 healthy subjects performed rebreathing tests to determine the ventilatory response to hypoxia, at different levels of carbon dioxide (CO2), and to normoxic hypercapnia.Oxygen saturation (SaO2), end-tidal CO2 (et-CO2), minute ventilation, blood pressure, R-R interval and mid-cerebral artery flow velocity (MCFV) were continuously recorded. The hypoxic ventilatory response significantly increased under hypercapnia and decreased under hypocapnia (slopes L/min/% Sa O2: –0.33±0.05, –0.74±0.02 and –1.59±0.3, p<0.0001, in hypocapnia, normocapnia and hypercapnia, respectively). At similar degrees of ventilation, MCFV increased more markedly during normocapnic hypoxia than normoxic hypercapnia; the slopes linking MCFV to hypoxia remained unchanged at increasing levels of et-CO2, whereas the regression lines were shifted upward. The R-R interval decreased more markedly during normocapnic hypoxia than normoxic hypercapnia and the arterial baroreflex sensitivity was decreased only by hypoxia. Cardiovascular responses to hypoxia were not affected by different levels of et-CO2. We conclude that concomitant hypoxia and hypercapnia, while increasing ventilation synergistically, exert an additive effect on cerebral blood flow. Increased sympathetic activity (and reduced baroreflex sensitivity) is one of the mechanisms by which hypoxia stimulates cardiac sympathetic activity.
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References
Abboud FM, MD Thames (1984) Interaction of cardiovascular reflexes in the circulatory control. In: Handbook of Physiology, The cardiovascular System. Peripheral Circulation and Organ Blood Flow. sect 2, vol III, part 2. Am Physiol Soc, Bethesda, pp 675–753
Ainslie PN, Poulin MJ (2004) Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide. J Appl Physiol 97:149–159
Bernardi L, Gabutti A, Porta C, Spicuzza L (2001) Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity. J Hypertens 19:2221–2229
Bernardi L, Hilz M, Stemper B, Passino C, Welsch G, Axelrod FB (2003) Respiratory and cerebrovascular responses to hypoxia and hypercapnia in familial dysautonomia. Am J Respir Crit Care Med 167:141–149
Bernardi L, Spadacini G, Bellwon J, Hajric R, Roskamm H, Frey AW (1998) Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure. Lancet 351:1308–1311
Brian JE, Faraci FM, Heistad DD (1996) Recent insights into the regulation of cerebral circulation. Clin Exp Pharmacol Physiol 23:449–457
Bristow JD, Brown EB, Cunningham JDC, Goode RC, Howson MO, Sleight P (1971) The effects of hypercapnia, hypoxia and ventilation on the baroreflex regulation of the pulse interval. J Physiol 216:281–302
Bristow JD, Brown EB, Cunningham JDC, Howson MH, Lee MJR, Pickering TO, Sleight P (1974) The effects of raising alveolar PCO2 and ventilation separately and together on the sensitivity and setting of the baroreceptor cardiodepressor reflex in man. J Physiol 243:401–425
Choi JY, Morris JC, Hsu CY (1998) Aging and cerebrovascular disease. Neurol Clin 16:687–711
Chugh SS, Chua TP, Coats AJ (1996) Peripheral chemoreflex in chronic heart failure: friend and foe. Am Heart J 132:900–904
Corne S, Webster K, Younes M (2003) Hypoxic respiratory response during acute stable hypocapnia. Am J Respir Crit Care Med 167:1193–1199
Ellingsen I, Hauge A, Nicolaysen G, Thoresen M, Walloe L (1987) Changes in human cerebral flow due to step changes in PAO2 and PACO2. Acta Physiol Scand 129:157–153
Fatemian M, Robbins PA (2001) Selected contribution: chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans. J Appl Physiol 90:1607–1614
Francis DA, Coats JS, Ponikowski P (2000) Chemoreflex-Baroreflex interactions in cardiovascular disease. In: Bradley TD, Floras JS (eds) Sleep Apnea. Implication in cardiovascular and cerebrovascular disease. Marcel Dekker, New York, pp 261–283
Gur AY, Bova I, Bornstein NM (1996) Is impaired cerebral vasomotor reactivity a predictive factor of stroke in asymptomatic patients? Stroke 27:2188–2190
Hackett PH, Roach RC (2001) Highaltitude illness. N Engl J Med 345:107–114
Halliwill JR, Minson CT (2002) Effect of hypoxia on arterial baroreflex control of heart rate and muscle nerve activity in humans. J Appl Physiol 93:857–864
Heistad DD, Abboud FM, Mark AL, Schnid PG (1974) Interaction of baroreceptor and chemoreceptor reflexes: modulation of the chemoreceptor reflex by changes in baroreceptor activity. J Clin Invest 53:1226–1236
Imray CH, Brearey S, Clarke T, Hale D, Morgan J, Walsh S, Wright AD (2000) Cerebral oxygenation at high altitude and the response to carbon dioxide, hyperventilation and oxygen. The Birmingham Medical Research Expeditionary Society. Clin Sci (Lond) 98:159–164
Jensen JB, Wright AD, Lassen NA, Harvey TC, Winterborn MH, Raichle ME, Bradwell AR (1990) Cerebral blood flow in acute mountain sickness. J Appl Physiol 69:430–433
Jordan J, Shannon JR,Diedrich A, Black B, Costa F, Robertson D, Biaggioni I (2000) Interaction of carbon dioxide and sympathetic nervous system activity in the regulation of cerebral perfusions in humans. Hypertension 36:383–388
Kemmotsu O, Ueda M, Otsuka H, Yamamura T, Winter DC, Eckerle JS (1991) Arterial tonometry for noninvasive, continuous blood pressure monitoring during anesthesia. Anesthesiology 75:333–340
Kongo M, Yamamoto R, Kobayashi M, Nosaka S (1999) Hypoxia inhibits baroreflex vagal bradycardia via a central action in anaesthetized rats. Exp Physiol 84:47–56
LeMarbre G, Stauber S, Khayat RN, Puleo DS, Skatrud JB, Morgan BJ (2003) Baroreflex-induced sympathetic activation does not alter cerebrovascular CO2 responsiveness in humans. J Physiol 551:609–616
Malliani A, Pagani M, Lombardi F, Cerutti S (1991) Cardiovascular neural regulation explored in the frequency domain. Circulation 84:482–492
Massik J, Jones MD Jr, Miyabe M, Tang YL, Hudak ML, Koehler RC, Traystman RJ (1989) Hypercapnia and response of cerebral blood flow to hypoxia in newborn lambs. J Appl Physiol 66:1065–1070
Milic-Emili J (1975) Clinical methods for assessing the ventilatory response to carbon dioxide and hypoxia. N Engl J Med 10:864–865
Ponikowski P, Chua TP, Piepoli M, Ondusova D, Webb-Peploe K, Harrington D, Anker SD, Volterrani M, Colombo R, Mazzuero G, Giordano A, Coats AJ (1997) Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure. Circulation 96:2586–2594
Ponikowski P, Francis DP, Piepoli MF, Davies LC, Chua TP, Davos CH, Florea V, Banasiak W, Poole-Wilson PA, Coats AJ, Anker SD (2001) Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation 102:967–972
Poulin MJ, Fatemian M, Tansley JG, O’Connor DF, Robbins PA (2002) Changes in cerebral blood flow during and after 48 h of both isocapnic and poikilocapnic hypoxia in humans. Exp Physiol 87:633–642
Quint SR, Scremin OU, Sonnenschein RR, Rubinstein EH (1980) Enhancement of cerebrovascular effect of CO2 by hypoxia. Stroke 3:286–289
Somers VK, Mark AL, Zavala DC, Abboud FM (1989) Influence of ventilation and hypocapnia on sympathetic responses to hypoxia in normal humans. J Appl Physiol 67:2095–2100
Somers VK, Mark AL, Zavala DC, Abboud FM (1989) Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J Appl Physiol 67:2101–2106
Somers VK, Mark AL, Abboud FM (1991) Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans. J Clin Invest 87:1953–1975
Spicuzza L, Gabutti A, Porta A, Montana N, Bernardi L (2000) Yoga and chemoreflex response to hypoxia and hypercapnia. Lancet 356:1495–1496
Vetner SF, Priano LL, Rutheford JD, Manders WT (1980) Sympathetic regulation of the cerebral circulation by the carotid chemoreceptors reflex. Am J Physiol 238:H594–H598
Xie A, Skatrud JB, Puleo DS, Morgan BJ (2001) Exposure to hypoxia produces long-lasting sympathetic activation in humans. J Appl Physiol 91:1555–1562
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Spicuzza, L., Porta, C., Bramanti, A. et al. Interaction between central-peripheral chemoreflexes and cerebro-cardiovascular control. Clin Auton Res 15, 373–381 (2005). https://doi.org/10.1007/s10286-005-0284-5
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DOI: https://doi.org/10.1007/s10286-005-0284-5