Downloaded from http://journals.lww.com/acsm-msse by BhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eJPG+b4DlKuAX44qu/vwzmc= on 07/30/2018 Copyright @ 200 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited. 8 Caffeine Stimulates Ventilation in Athletes with Exercise-Induced Hypoxemia ROBERT F. CHAPMAN and JOEL M. STAGER Human Performance Laboratory, Department of Kinesiology, Indiana University, Bloomington, IN ABSTRACT CHAPMAN, R. F., and J. M. STAGER. Caffeine Stimulates Ventilation in Athletes with Exercise-Induced Hypoxemia. Med. Sci. Sports Exerc., Vol. 40, No. 6, pp. 1080–1086, 2008. Introduction/Purpose: Many athletes with exercise-induced hypoxemia (EIH) show an insufficient ventilatory response to exercise and low resting ventilatory responsiveness. The purpose of this project was to determine whether a moderate dosage of caffeine, a common ventilatory stimulant, could augment resting ventilatory responsiveness, exercise ventilation (V ˙ E ), end-tidal O 2 partial pressure (PETO 2 ), and arterial oxyhemoglobin saturation (HbSaO 2 ) in athletes with EIH. Methods: Eight highly trained males (V ˙ O 2max , 69.2 T 4.0 mLI[kgImin] j1 ) who demonstrated EIH at V ˙ O 2max (HbSaO 2 , 88.0 T 1.7%), ingested in a randomized design a placebo or caffeine (CAF, 8 mgIkg j1 body wt) 1 h before testing. Ventilatory responsiveness at rest was assessed via the isocapnic hypoxic and hyperoxic hypercapnic ventilatory responses (HVR and HCVR, respectively). Dependent measures of metabolic variables, ventilation, and saturation were determined during progressive treadmill exercise to exhaustion. Results: V ˙ E was higher at 75%, 80%, and 100% of V ˙ O 2max with CAF (P G 0.05). V ˙ E /V ˙ O 2 ,PETO 2 , and HbSaO 2 were increased at 75%, 80%, and 90% of V ˙ O 2max with CAF but were not different at V ˙ O 2max despite an increase in V ˙ E. No change in V ˙ O 2max was observed between treatments. HVR and HCVR were not different between the two conditions, indicating that the increased V ˙ E likely came from central stimulation or secondary effects of CAF. Conclusion: The failure of HbSaO 2 to increase at V ˙ O 2max despite an increase in V ˙ E suggests that mechanisms influencing HbSaO 2 other than an inadequate hyperventilatory response may operate to different degrees across individuals as V ˙ O 2max is approached. Key Words: HYPOXIC VENTILATORY RESPONSE, HYPERCAPNIC VENTILATORY RESPONSE, PULMONARY DIFFUSION LIMITATIONS, ARTERIAL OXYHEMOGLOBIN SATURATION M any highly trained endurance athletes exhibit exercise-induced arterial hypoxemia (EIH) during heavy exercise at sea level (4,9,10,16,25). From an exercise performance standpoint, this phenomenon is of interest as the decreased arterial oxyhemoglobin saturation (HbSaO 2 ) associated with EIH may reduce O 2 delivery to the working muscles, possibly limiting V ˙ O 2max (9,25). Pulmonary gas exchange limitations, indicated by an excessively widened alveolar–arterial O 2 pressure differ- ence (A-aDO 2 ), have been identified as a primary determi- nant of the reduced HbSaO 2 and arterial PO 2 (PaO 2 ) in EIH subjects (10,36). However, many athletes with EIH also demonstrate a reduced hyperventilatory response during exercise, resulting in an alveolar O 2 partial pressure (PAO 2 ) that is inadequate to maintain PaO 2 near resting levels as exercise workload increases (10,16). By increasing PAO 2 during exercise in EIH athletes, it may be possible to determine the nature of the ventilatory role in the formation of the hypoxemia or determine whether hypoxemia could be prevented or mitigated. PAO 2 has been directly increased in EIH athletes with a mildly hyperoxic inspirate, reducing the hypoxemia and improving V ˙ O 2max (10,25). PAO 2 may also be increased during exercise by increasing alveolar ventilation that is reportedly lower in EIH athletes compared with normoxic athletes (10,16). During submaximal exercise, stimulating ventilation (V ˙ E ) in trained athletes has been successfully accomplished with a mildly hypercapnic inspirate (18), a mildly hypoxic inspirate (3,4), increased dead space (21), and with pharmacologically augmented peripheral chemo- sensitivity (15,22). However, during maximal exercise, many highly trained endurance athletes reach an expiratory flow limit due to mechanical constraints of the chest wall and, subsequently, are unable to further increase V ˙ E despite the presence of potent chemical stimuli (3,12,18). Increas- ing alveolar ventilation may also increase the work of breathing, which has been shown to negatively affect skeletal muscle blood flow and exercise performance (17). Therefore, it is unknown if ventilation during heavy or maximal exercise could be augmented in EIH athletes or if an increase in maximal V ˙ E could improve end-exercise HbSaO 2 or V ˙ O 2max . In examining potential ventilatory stimulants, caffeine has been historically cited for its stimulating effects on respiration (20,28). Clinically, xanthine compounds have been used as safe and effective ventilatory stimulants for the Address for correspondence: Robert F. Chapman, Ph.D., Department of Kinesiology, Indiana University, HPER 112, Bloomington, IN 47405; E-mail: rfchapma@indiana.edu. Submitted for publication October 2007. Accepted for publication December 2007. 0195-9131/08/4006-1080/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE Ò Copyright Ó 2008 by the American College of Sports Medicine DOI: 10.1249/MSS.0b013e3181667421 1080 BASIC SCIENCES