Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure

Department of Cardiac Medicine, Royal Brompton Hospital, London, England.

OBJECTIVES: This study sought to establish the chemosensitivity of patients with chronic heart failure. BACKGROUND: The ventilatory response to exercise is often increased in patients with chronic heart failure, as characterized by the steeper regression slope relating minute ventilation to carbon dioxide output. We hypothesized that the sensitivity of chemoreceptors may be reset and may in part mediate the exercise hyperpnea seen in this condition. METHODS: Hypoxic and peripheral hypercapnic chemosensitivity were studied in 38 patients with chronic heart failure (35 men, 3 women; mean [+/-SE] age 60.2 +/- 1.3 years; radionuclide left ventricular ejection fraction 25.7 +/- 2.3%) and 15 healthy control subjects (11 men, 4 women; mean age 54.9 +/- 3.0 years) using transient inhalations of pure nitrogen and single breaths of 13% carbon dioxide, respectively. The change in chemosensitivity during mild exercise (25 W) was assessed in the first 15 patients and all control subjects. Central hypercapnic chemosensitivity was also characterized in 25 patients and 10 control subjects by the rebreathing of 7% carbon dioxide in 93% oxygen. Cardiopulmonary exercise testing was performed in all subjects. RESULTS: Maximal oxygen consumption was 16.6 +/- 0.9 versus 29.7 +/- 2.2 mol/kg per min (p < 0.0001), and the ventilation-carbon dioxide output regression slope was 37.2 +/- 1.5 versus 26.5 +/- 1.4 (p < 0.0001) in patients and control subjects, respectively. Hypoxic and central hypercapnic chemosensitivity were enhanced in patients (0.707 +/- 0.076 vs. 0.293 +/- 0.056 liters/min per % arterial oxygen saturation [SaO2], p = 0.0001 and 3.15 +/- 0.41 vs. 2.02 +/- 0.25 liters/min per mm Hg, p = 0.025, respectively) and correlated significantly with the ventilatory response to exercise. Hypoxic chemosensitivity was augmented during exercise in patients and in control subjects but remained higher in the former (1.530 +/- 0.27 vs. 0.685 +/- 0.12 liters/min per %SaO2, p = 0.01). The peripheral hypercapnic chemosensitivity of patients at rest and during exercise was similar to that in control subjects, consistent with its lesser contribution to overall carbon dioxide chemosensitivity. CONCLUSIONS: Enhanced hypoxic and central hypercapnic chemosensitivity may play a role in mediating the increased ventilatory response to exercise in chronic heart failure.

This article has been cited by other articles:

				A. Giannoni, M. Emdin, F. Bramanti, G. Iudice, D. P. Francis, A. Barsotti, M. Piepoli, and C. Passino Combined increased chemosensitivity to hypoxia and hypercapnia as a prognosticator in heart failure. J. Am. Coll. Cardiol., May 26, 2009; 53(21): 1975 - 1980. [Abstract] [Full Text] [PDF]

				Y.-L. Li, Y. Ding, C. Agnew, and H. D. Schultz Exercise training improves peripheral chemoreflex function in heart failure rabbits J Appl Physiol, September 1, 2008; 105(3): 782 - 790. [Abstract] [Full Text] [PDF]

				A. Di Vanna, A. M. F. W. Braga, M. C. Laterza, L. M. Ueno, M. U. P. B. Rondon, A. C. P. Barretto, H. R. Middlekauff, and C. E. Negrao Blunted muscle vasodilatation during chemoreceptor stimulation in patients with heart failure Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H846 - H852. [Abstract] [Full Text] [PDF]

				H. D. Schultz, Y. L. Li, and Y. Ding Arterial Chemoreceptors and Sympathetic Nerve Activity: Implications for Hypertension and Heart Failure Hypertension, July 1, 2007; 50(1): 6 - 13. [Full Text] [PDF]

				D. Mancini and T. H. LeJemtel Is Ventilatory Classification Preferable to Peak Oxygen Consumption for Risk Stratification in Heart Failure? Circulation, May 8, 2007; 115(18): 2376 - 2378. [Full Text] [PDF]

				G. Tumminello, M. Guazzi, P. Lancellotti, and L. A. Pierard Exercise ventilation inefficiency in heart failure: pathophysiological and clinical significance Eur. Heart J., March 2, 2007; 28(6): 673 - 678. [Abstract] [Full Text] [PDF]

				P. Agostoni, M. Contini, A. Magini, A. Apostolo, G. Cattadori, M. Bussotti, F. Veglia, D. Andreini, and P. Palermo Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia Eur J Heart Fail, November 1, 2006; 8(7): 729 - 735. [Abstract] [Full Text] [PDF]

				M. F. Piepoli, A. Kaczmarek, D. P. Francis, L. C. Davies, M. Rauchhaus, E. A. Jankowska, S. D. Anker, A. Capucci, W. Banasiak, and P. Ponikowski Reduced Peripheral Skeletal Muscle Mass and Abnormal Reflex Physiology in Chronic Heart Failure Circulation, July 11, 2006; 114(2): 126 - 134. [Abstract] [Full Text] [PDF]

				Y.-L. Li, X.-H. Xia, H. Zheng, L. Gao, Y.-F. Li, D. Liu, K. P. Patel, W. Wang, and H. D. Schultz Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits Cardiovasc Res, July 1, 2006; 71(1): 129 - 138. [Abstract] [Full Text] [PDF]

				K. Dimopoulos, D. O. Okonko, G.-P. Diller, C. S. Broberg, T. V. Salukhe, S. V. Babu-Narayan, W. Li, A. Uebing, S. Bayne, R. Wensel, et al. Abnormal Ventilatory Response to Exercise in Adults With Congenital Heart Disease Relates to Cyanosis and Predicts Survival Circulation, June 20, 2006; 113(24): 2796 - 2802. [Abstract] [Full Text] [PDF]

				A. Ciarka, N. Cuylits, J.-L. Vachiery, M. Lamotte, J.-P. Degaute, R. Naeije, and P. van de Borne Increased Peripheral Chemoreceptors Sensitivity and Exercise Ventilation in Heart Transplant Recipients Circulation, January 17, 2006; 113(2): 252 - 257. [Abstract] [Full Text] [PDF]

				R. Wensel, D. P. Francis, P. Georgiadou, A. Scott, S. Genth-Zotz, S. D. Anker, A. J.S. Coats, and M. F. Piepoli Exercise hyperventilation in chronic heart failure is not caused by systemic lactic acidosis Eur J Heart Fail, December 1, 2005; 7(7): 1105 - 1111. [Abstract] [Full Text] [PDF]

				J. Spaak, Z. J. Egri, T. Kubo, E. Yu, S.-I. Ando, Y. Kaneko, K. Usui, T. D. Bradley, and J. S. Floras Muscle Sympathetic Nerve Activity During Wakefulness in Heart Failure Patients With and Without Sleep Apnea Hypertension, December 1, 2005; 46(6): 1327 - 1332. [Abstract] [Full Text] [PDF]

				D. J. Paterson Targeting Arterial Chemoreceptor Over-Activity in Heart Failure With a Gas Circ. Res., August 5, 2005; 97(3): 201 - 203. [Full Text] [PDF]

				Y.-L. Li, Y.-F. Li, D. Liu, K. G. Cornish, K. P. Patel, I. H. Zucker, K. M. Channon, and H. D. Schultz Gene Transfer of Neuronal Nitric Oxide Synthase to Carotid Body Reverses Enhanced Chemoreceptor Function in Heart Failure Rabbits Circ. Res., August 5, 2005; 97(3): 260 - 267. [Abstract] [Full Text] [PDF]

				K. K.A. Witte, S. Thackray, N. P. Nikitin, J. G.F. Cleland, and A. L. Clark The effects of long-term {beta}-blockade on the ventilatory responses to exercise in chronic heart failure Eur J Heart Fail, June 1, 2005; 7(4): 612 - 617. [Abstract] [Full Text] [PDF]

				A. Ciarka, B. Najem, N. Cuylits, M. Leeman, O. Xhaet, K. Narkiewicz, M. Antoine, J.-P. Degaute, and P. van de Borne Effects of Peripheral Chemoreceptors Deactivation on Sympathetic Activity in Heart Transplant Recipients Hypertension, May 1, 2005; 45(5): 894 - 900. [Abstract] [Full Text] [PDF]

				M. Arzt, M. Schulz, R. Wensel, S. Montalvan, F. C. Blumberg, G. A. J. Riegger, and M. Pfeifer Nocturnal Continuous Positive Airway Pressure Improves Ventilatory Efficiency During Exercise in Patients With Chronic Heart Failure Chest, March 1, 2005; 127(3): 794 - 802. [Abstract] [Full Text] [PDF]

				M. Guazzi, G. Reina, G. Tumminello, and M. D. Guazzi Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure Eur. Heart J., March 1, 2005; 26(5): 472 - 480. [Abstract] [Full Text] [PDF]

				A Rao and D Gray Impact of heart failure on quality of sleep Postgrad. Med. J., February 1, 2005; 81(952): 99 - 102. [Abstract] [Full Text] [PDF]

				K. K.A. Witte and A. L. Clark The effect of aspirin on the ventilatory response to exercise in chronic heart failure Eur J Heart Fail, October 1, 2004; 6(6): 745 - 748. [Abstract] [Full Text] [PDF]

				S. Glaser, C. F. Opitz, U. Bauer, R. Wensel, R. Ewert, P. E. Lange, and F. X. Kleber Assessment of Symptoms and Exercise Capacity in Cyanotic Patients With Congenital Heart Disease Chest, February 1, 2004; 125(2): 368 - 376. [Abstract] [Full Text] [PDF]

				R. Wolk, B. D. Johnson, and V. K. Somers Leptin and the ventilatory response to exercise in heart failure J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1644 - 1649. [Abstract] [Full Text] [PDF]

				K K A Witte, S D R Thackray, N P Nikitin, J G F Cleland, and A L Clark The effects of {alpha} and {beta} blockade on ventilatory responses to exercise in chronic heart failure Heart, October 1, 2003; 89(10): 1169 - 1173. [Abstract] [Full Text] [PDF]

				K K A Witte, S D R Thackray, N P Nikitin, J G F Cleland, and A L Clark Pattern of ventilation during exercise in chronic heart failure Heart, June 1, 2003; 89(6): 610 - 614. [Abstract] [Full Text] [PDF]

				M. Arzt, M. Harth, A. Luchner, F. Muders, S. R. Holmer, F. C. Blumberg, G. A.J. Riegger, and M. Pfeifer Enhanced Ventilatory Response to Exercise in Patients With Chronic Heart Failure and Central Sleep Apnea Circulation, April 22, 2003; 107(15): 1998 - 2003. [Abstract] [Full Text] [PDF]

				T Tomita, H Takaki, Y Hara, F Sakamaki, T Satoh, S Takagi, Y Yasumura, N Aihara, Y Goto, and K Sunagawa Attenuation of hypercapnic carbon dioxide chemosensitivity after postinfarction exercise training: possible contribution to the improvement in exercise hyperventilation Heart, April 1, 2003; 89(4): 404 - 410. [Abstract] [Full Text] [PDF]

				S. Andreas, C. Bingeli, P. Mohacsi, T. F. Luscher, and G. Noll Nasal Oxygen and Muscle Sympathetic Nerve Activity in Heart Failure Chest, February 1, 2003; 123(2): 366 - 371. [Abstract] [Full Text] [PDF]

				P. Agostoni, M. Guazzi, M. Bussotti, S. De Vita, and P. Palermo Carvedilol Reduces the Inappropriate Increase of Ventilation During Exercise in Heart Failure Patients Chest, December 1, 2002; 122(6): 2062 - 2067. [Abstract] [Full Text] [PDF]

				T Kohnlein, T Welte, L B Tan, and M W Elliott Central sleep apnoea syndrome in patients with chronic heart disease: a critical review of the current literature Thorax, June 1, 2002; 57(6): 547 - 554. [Abstract] [Full Text] [PDF]

				P. P. Ponikowski, T. P. Chua, D. P. Francis, A. Capucci, A. J.S. Coats, and M. F. Piepoli Muscle Ergoreceptor Overactivity Reflects Deterioration in Clinical Status and Cardiorespiratory Reflex Control in Chronic Heart Failure Circulation, November 6, 2001; 104(19): 2324 - 2330. [Abstract] [Full Text] [PDF]

				A. J S Coats HEART FAILURE: What causes the symptoms of heart failure? Heart, November 1, 2001; 86(5): 574 - 578. [Full Text] [PDF]

				J. A. Soares Barreto-Filho, F. M. Consolim-Colombo, H. Ferreira Lopes, C. R. Martins Sobrinho, G. M. Guerra-Riccio, and E. M. Krieger Dysregulation of Peripheral and Central Chemoreflex Responses in Chagas' Heart Disease Patients Without Heart Failure Circulation, October 9, 2001; 104(15): 1792 - 1798. [Abstract] [Full Text] [PDF]

				P. Ponikowski, T. P. Chua, S. D. Anker, D. P. Francis, W. Doehner, W. Banasiak, P. A. Poole-Wilson, M. F. Piepoli, and A. J.S. Coats Peripheral Chemoreceptor Hypersensitivity: An Ominous Sign in Patients With Chronic Heart Failure Circulation, July 31, 2001; 104(5): 544 - 549. [Abstract] [Full Text] [PDF]

				M. Cicoira, L. Zanolla, L. Franceschini, A. Rossi, G. Golia, M. Zamboni, P. Tosoni, and P. Zardini Skeletal muscle mass independently predicts peak oxygen consumption and ventilatory response during exercise in noncachectic patients with chronic heart failure J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2080 - 2085. [Abstract] [Full Text] [PDF]

				P. Ponikowski, D. P. Francis, M. F. Piepoli, L. C. Davies, T. P. Chua, C. H. Davos, V. Florea, W. Banasiak, P. A. Poole-Wilson, A. J. S. Coats, et al. 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, February 20, 2001; 103(7): 967 - 972. [Abstract] [Full Text] [PDF]

				Recommendations for exercise testing in chronic heart faliure patients Eur. Heart J., January 1, 2001; 22(1): 37 - 45. [PDF]

				G. D. Pinna, R. Maestri, A. Mortara, M. T. L. Rovere, F. Fanfulla, and P. Sleight Periodic breathing in heart failure patients: testing the hypothesis of instability of the chemoreflex loop J Appl Physiol, December 1, 2000; 89(6): 2147 - 2157. [Abstract] [Full Text] [PDF]

				P. SOLIN, T. ROEBUCK, D. P. JOHNS, E. HAYDN WALTERS, and M. T. NAUGHTON Peripheral and Central Ventilatory Responses in Central Sleep Apnea with and without Congestive Heart Failure Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2194 - 2200. [Abstract] [Full Text]

				T Reybrouck, L Mertens, S Brusselle, M Weymans, B Eyskens, J Defoor, and M Gewillig Oxygen uptake versus exercise intensity: a new concept in assessing cardiovascular exercise function in patients with congenital heart disease Heart, July 1, 2000; 84(1): 46 - 52. [Abstract] [Full Text] [PDF]

				N G Mahon, S Sharma, P M Elliott, M K Baig, M W Norman, S Barbeyto, and W J McKenna Abnormal cardiopulmonary exercise variables in asymptomatic relatives of patients with dilated cardiomyopathy who have left ventricular enlargement Heart, May 1, 2000; 83(5): 511 - 517. [Abstract] [Full Text]

				G. D. Pinna, R. Maestri, A. Mortara, and M. T. L. Rovere Cardiorespiratory interactions during periodic breathing in awake chronic heart failure patients Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H932 - H941. [Abstract] [Full Text] [PDF]

				L C Davies, D P Francis, M Piepoli, A C Scott, P Ponikowski, and A J S Coats Chronic heart failure in the elderly: value of cardiopulmonary exercise testing in risk stratification Heart, February 1, 2000; 83(2): 147 - 151. [Abstract] [Full Text]

				I. Wilcox, S. G. McNamara, C. E. Sullivan, D. D. Sin, G. C. Man, R. L. Jones, and S. Javaheri Central Sleep Apnea and Heart Failure N. Engl. J. Med., January 27, 2000; 342(4): 293 - 294. [Full Text]

				V.G. Florea, M.Y. Henein, S.D. Anker, D.P. Francis, J.S. Chambers, P. Ponikowski, and A.J.S. Coats Prognostic value of changes over time in exercise capacity and echocardiographic measurements in patients with chronic heart failure Eur. Heart J., January 2, 2000; 21(2): 146 - 153. [Abstract] [PDF]

				D.P. Francis, W. Shamim, L.C. Davies, M.F. Piepoli, P. Ponikowski, S.D. Anker, and A.J.S. Coats Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from VE/VCO2slope and peak VO2 Eur. Heart J., January 2, 2000; 21(2): 154 - 161. [Abstract] [PDF]

				P. Ponikowski, S. D. Anker, T. P. Chua, D. Francis, W. Banasiak, P. A. Poole-Wilson, A. J. S. Coats, and M. Piepoli Oscillatory Breathing Patterns During Wakefulness in Patients With Chronic Heart Failure : Clinical Implications and Role of Augmented Peripheral Chemosensitivity Circulation, December 14, 1999; 100(24): 2418 - 2424. [Abstract] [Full Text] [PDF]

				P. Ponikowski, M. Piepoli, T.P. Chua, W. Banasiak, D. Francis, S.D. Anker, and A.J.S. Coats The impact of cachexia on cardiorespiratory reflex control in chronic heart failure Eur. Heart J., November 2, 1999; 20(22): 1667 - 1675. [Abstract] [PDF]

				M Piepoli Editorials: Diagnostic and prognostic indicators in chronic heart failure Eur. Heart J., October 1, 1999; 20(19): 1367 - 1369. [PDF]

				D. P. Francis, L. C. Davies, M. Piepoli, M. Rauchhaus, P. Ponikowski, and A. J. S. Coats Origin of Oscillatory Kinetics of Respiratory Gas Exchange in Chronic Heart Failure Circulation, September 7, 1999; 100(10): 1065 - 1070. [Abstract] [Full Text] [PDF]

				K. Narkiewicz, C. A. Pesek, P. J. H. van de Borne, M. Kato, and V. K. Somers Enhanced Sympathetic and Ventilatory Responses to Central Chemoreflex Activation in Heart Failure Circulation, July 20, 1999; 100(3): 262 - 267. [Abstract] [Full Text] [PDF]

				S.-Y. Sun, W. Wang, I. H. Zucker, and H. D. Schultz Enhanced peripheral chemoreflex function in conscious rabbits with pacing-induced heart failure J Appl Physiol, April 1, 1999; 86(4): 1264 - 1272. [Abstract] [Full Text] [PDF]

				S.-Y. Sun, W. Wang, I. H. Zucker, and H. D. Schultz Enhanced activity of carotid body chemoreceptors in rabbits with heart failure: role of nitric oxide J Appl Physiol, April 1, 1999; 86(4): 1273 - 1282. [Abstract] [Full Text] [PDF]

				N. Francis, A. Cohen-Solal, and D. Logeart Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H913 - H917. [Abstract] [Full Text] [PDF]

				P. van de Borne, R. Oren, and V. K. Somers Dopamine Depresses Minute Ventilation in Patients With Heart Failure Circulation, July 14, 1998; 98(2): 126 - 131. [Abstract] [Full Text] [PDF]

				P. Ponikowski, T. P. Chua, M. Piepoli, D. Ondusova, K. Webb-Peploe, D. Harrington, S. D. Anker, M. Volterrani, R. Colombo, G. Mazzuero, et al. Augmented Peripheral Chemosensitivity as a Potential Input to Baroreflex Impairment and Autonomic Imbalance in Chronic Heart Failure Circulation, October 21, 1997; 96(8): 2586 - 2594. [Abstract] [Full Text]