Japanese Journal of Physiology, 50, 449–455, 2000 Respiratory Compensation Point during Incremental Exercise as Related to Hypoxic Ventilatory Chemosensitivity and Lactate Increase in Man Nariko TAKANO Physiology Laboratory, Department of School Health, Faculty of Education, Kanazawa University, Kanazawa, 920–1192 Japan Abstract: The pulmonary ventilation–O up- sures were normalized for body surface area. In ~ ~ 2 take (VE-VO2) relationship during incremental ex- the males, the individual difference in RCP was ercise has two inflection points: one at a lower inversely correlated with those of HVR and V~O , termed the ventilatory threshold (VT); and Dslope (p,0.05), and in the females, similar ten- 2 ~ another at a higher VO2, the respiratory compen- dencies persisted, while the correlation did not sation point (RCP). The individuality of RCP was reach statistically significant levels (0.05,p, studied in relation to those of the chemosensitivi- 0.1). There was no significant correlation be- ties of the central and peripheral chemorecep- tween RCP and HCVR in either sex. A multiple tors, which were assessed by resting estimates linear regression analysis showed that 40 to 50% of hypercapnic ventilatory response (HCVR) and of the variance of RCP was accounted for by hypoxic ventilatory response (HVR), respectively, those of HVR and Dslope, both of which were re- and the rate of lactic acid increase during exer- lated linearly and additively to RCP, this relation cise, which was estimated as a slope difference being manifested in the males but not in the fe- (Dslope) between a lower slope of V~CO -V~O re- males without consideration of the menstrual ~ 2 2 lationship (VCO2: CO2 output) obtained at work cycle. These results suggest that the individuality rates below VT and a higher slope at work rates of RCP depends partly on the chemosensitivity between VT and RCP. Twenty-two male and six- of the carotid bodies and the rate of lactic acid in- teen female subjects underwent a 1 min incre- crease during incremental exercise. [Japanese mental exercise test until exhaustion, in which Journal of Physiology, 50, 449–455, 2000] VT, RCP and Dslope were determined. All mea- Key words: heavy exercise, respiratory compensation point, exercise hyperpnea, carotid body, lactic acidosis. ~ ~ ~ During incremental exercise in normal humans, pul- steeper increase in VE against VO2 occurs. The VO2 monary ventilation (V~E) linearly increases with in- point of the onset of this V~E augmentation is termed ~ ~ creasing O2 uptake (VO2), but the increment of VE the respiratory compensation point (RCP), above ~ ~ ~ against VO2 becomes steeper at two VO2 points [1]. which the VE augmentation (hyperventilation) induces ~ The first inflection point, occurring at a lower VO2, is a fall in arterial PCO2, with resulting constraint of fur- termed the ventilatory threshold (VT) [2], above ther falls of arterial pH due to severer lactic acidosis which various kinds of ventilatory stimuli such as a [7]. Peripheral chemoreceptors have been implicated fall in arterial pH due to lactic acidosis, hyperkalemia as the site at which the ventilatory stimuli act because and augumentation of arterial PCO2 oscillation are of the absence of compensatory hyperventilation and newly induced [3–6]. With further increases in the subsequent fall in PCO2 during heavy exercise in ventilatory stimuli as exercise becomes heavier, a carotid body–resected patients [8, 9]. Received on April 24, 2000; accepted on July 13, 2000 Correspondence should be addressed to: Nariko Takano, Physiology Laboratory, Department of School Health, Faculty of Education, Kanazawa University, Kanazawa, 920–1192 Japan. Tel: 181–76–264–5568, Fax: 181–76–234–4117, E-mail: [email protected] Japanese Journal of Physiology Vol. 50, No. 4, 2000 449 N. TAKANO We hypothesized that, in individuals with greater tics are shown in Table 1. Body surface area was cal- carotid body chemosensitivities, compensatory hyper- culated from the height and weight measurements ventilation would begin at lower work rates at which using calculation formulas for Japanese men and smaller changes in the concentration of ventilatory women [19]. The subjects were all healthy non-smok- stimuli to the carotid bodies would be associated. The ers, of which 15 subjects were training as short and present study was undertaken to test this hypothesis. middle-distance runners, 4 subjects as long-distance In addition, involvement of central chemosensitivity runners in after-class activities, and 18 subjects were in the individual variance of RCP was also investi- taking part in recreational sports. Because of the vary- gated. Peripheral chemosensitivity was assessed by ing sports training status, physical fitness levels that hypoxic ventilatory responsiveness (HVR) and central were evaluated as maximum O2 uptake differed chemosensitivity by hypercapnic ventilatory respon- greatly among the subjects (Table 1). No special con- siveness (HCVR), both at rest. Since it has been re- sideration for menstrual cycle was given for the fe- ported that HVR [10–12] and HCVR [13] increase male subjects, to whom the phases of the menstrual with increasing exercise intensity, and that the exer- cycle on the day of the study were not inquired. cise estimates of HVR depend on the resting estimates Measurements. During the tests, the subjects of HVR [11, 12, 14], the individual differences in ex- breathed through a respiratory mask (dead space, ercise estimates of chemosensitivities at varying work 200 ml) to which a hot-wire flowmeter was fixed in rates were assumed to be predicted from those in the order to measure respiratory flow. Respiratory gas was resting estimates. continuously sampled (200 ml/min) from a nostril and Cooper et al. [15] divided the CO2 output–O2 up- introduced into a CO2-O2 gas analyzer (MG-360, Mi- ~ ~ take (VCO2-VO2) relationship up to RCP during incre- nato Medical Co., Japan), with which the CO2 and O2 mental exercise into two linear components. The inter- concentrations were analyzed through infrared ab- section point of the two linear components per se has sorption and zirconium oxide reaction, respectively. been described as V-slope AT (AT: anaerobic thresh- Signals from the flowmeter and gas analyzer were fed ~ old, expressed in terms of VO2 level) and a more reli- into a signal processor (RM-200, Respiromonitor, Mi- able, non-invasive estimate of AT [7]. It has been ar- nato Medical Co., Japan) and processed breath-by- ~ gued that the lower linear component with a lower breath to obtain pulmonary ventilation (VE), O2 up- ~ ~ ~ ~ slope (S1) in the VCO2-VO2 relationship reflects the take (VO2), CO2 output (VCO2), ventilatory equiva- ~ ~ ~ ~ aerobic metabolism (respiratory quotient) of the work- lents for O2 and CO2 (VE/VO2 and VE/VCO2, respec- ing muscles and the upper linear component with a tively) and end-tidal PO2 and PCO2. Heart rate (HR) higher slope (S2), aerobic metabolism plus “excess was monitored through an electrocardiogram. Arterial CO2” derived from bicarbonate buffering of lactic acid oxygen saturation (SO2) was measured using a finger taking place intramuscularly and extracellularly [16] if oximeter (Pulsox 8, Canon Co., Japan). the body CO2 stores are stable [15, 17]. Therefore, it Tests. Three tests were given to the subjects in would be assumed that the difference between S2 and the following order. Before the tests, the subjects un- S1 reflects an “approximate” rate of lactic acid in- derwent a training session in order to familiarize them crease occurring intramuscularly and extracellularly, with the equipment for the tests. although it does not reflect the “total” amount of lactic Transient hypoxic test for HVR assessment. This acid increase in the body fluids, a small portion of was based on the method of Shaw et al. [20]. A reser- which is buffered by the non-bicarbonate buffer sys- voir bag containing pure N2 was connected to the res- ~ tem [18]. In the present study, the difference of S2 and piratory mask. After VE and HR reached a steady S1 (Dslope) was also examined and used as an esti- state during air breathing, the inspired gas was mate of the rate of lactic acid increase at the work switched to N2 and three to eight breaths of N2 were rates below RCP. The aim of this was to explore the imposed on the subjects, followed by air breathing. relationship between the rate of lactic acid increase Subsequent hypoxic transients with a different number and RCP during incremental exercise (i.e., whether of N2 breaths were resumed after end-tidal PO2, SO2 the greater the former is, the lower the latter is). and HR returned to air-breathing levels. If SO2 levels during N2 breathing approached 70%, the subject was ~ METHODS switched back to room air. The highest VE (actually calculated as the mean value of the two highest con- ~ Subjects. Twenty-two male students and sixteen secutive VE) and the lowest SO2 achieved during the female students volunteered for this study after giving period of N2 breathing were obtained for each hypoxic written, informed consent. Their physical characteris- transient. Then, using the data from all six hypoxic 450 Japanese Journal of Physiology Vol. 50, No. 4, 2000 RCP during Incremental Exercise transients, a linear regression of the highest V~E and using Pearson’s correlation coefficients. Comparisons the lowest SO2 was analyzed for each subject by the in the measurements between male and female sub- least-squares method. The slope of the regression line, jects were analyzed using Welch’s test for unpaired ~ DVE/–DSO2, was designated as hypoxic ventilatory re- samples. The level of p,0.05 was considered to be sponsiveness (HVR). significant. CO2 rebreathing test for HCVR assessment. This ~ was based on the method of Read [21]. After VE and RESULTS HR reached a steady state during air breathing, the subjects rebreathed a 7% CO2–93% O2 gas contained Mean results of the measurements and the variability in a reservoir bag for 4 min, during which end-tidal among the subjects are shown in Table 1 for each sex.