Neural regulation of discontinuous gas exchange in Periplaneta americana

Patterns of gas exchange among terrestrial arthropods are highly variable from continuous to discontinuous with discretely partitioned phases. The underlying initiation and co-ordination of these patterns is relatively poorly understood. Here we present a novel method for the simultaneous measurement of central nervous system (CNS) activity of the metathoracic ganglion and VCO(2) in medium to large sized live terrestrial arthropods. Using Periplaneta americana at four oxygen levels (40%, 21%, 10% and 2% at 25 degrees C; n=6 per treatment), we present minimally invasive visualization of nervous output relative to typical resting discontinuous gas exchange (DGE) data for the first time. DGE was maintained when cockroaches were exposed to hyperoxia or moderate hypoxia, but was lost in severe hypoxia. CNS activity was manifested in three signal types: large CNS output coinciding with peak CO(2) production during a burst, moderate CNS output coinciding with CO(2) sawtoothing and fluttering, and minimal CNS activity during the closed phase of DGE in normoxia. Large and moderate CNS outputs were associated with observed abdominal pumping and congruent CO(2) peaks. At 10% oxygen, VCO(2) was significantly elevated during the inter-burst period in association with almost constant moderate CNS output between the periodic large CNS output. At 2% oxygen, DGE and large CNS output are lost to continuous CO(2) release and largely continuous moderate CNS output. As previously reported for this species, a central pattern generator for ventilation in the metathoracic ganglion is supported and we infer the presence of localized oxygen chemoreceptors based on clear CNS response to a change in oxygen tension.     

Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load

We examined the role of the carotid chemoreceptors in the ventilatory response to changes in venous CO2 load in 12 awake sheep using a venovenous extracorporeal perfusion circuit and two carbon dioxide membrane lungs (CDML). Three of the sheep had undergone surgical denervation of the carotid bodies (CBD). In the nine intact sheep, as CO2 was removed from or added to the peripheral venous blood through the CDML under normoxic conditions, there was a linear relationship between the rate of pulmonary CO2 excretion (VCO2) and the resulting rate of ventilation over a VCO2 range of 0--800% of control, so that arterial PCO2 remained close to isocapnic. In contrast, in the three CBD sheep, the ventilatory response to changes in VCO2 was significantly decreased under normoxic conditions, resulting in marked hypercapnia. The results indicate that the carotid chemoreceptors exert a major influence on the ventilatory response to changes in venous CO2 load.     

Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs.

To determine if a long-lasting increase in normoxic ventilatory drive is induced in conscious animals by repetitive hypoxia, we examined the normoxic [arterial O2 saturation (SaO2) > 93%] ventilatory response following successive episodes of 2-min eucapnic hypoxic challenges (SaO2 = 80%) in awake tracheotomized dogs. End-tidal CO2 was maintained at the resting level during and after repetitive hypoxia. The experimental protocol was performed twice in each of five dogs on separate days. To determine if changes in normoxic ventilation occurred between episodes of repetitive hypoxia, data were compared from six periods (epochs) for all experiments. The mean minute ventilation (VI) during three normoxic periods between episodes of intermittent hypoxia was 135, 154, and 169% of control (P < 0.05). VI during a 30-min recovery period was still higher at 183 and 172% of control (P < 0.05). Normoxic VI between hypoxic and recovery periods was significantly higher than the corresponding values in sham experiments. Our results indicate that a long-lasting increase in normoxic ventilation can be evoked in an awake unanesthetized dog by a short exposure to repetitive hypoxia.     

Ventilatory responses to specific CNS hypoxia in sleeping dogs.

Our study was concerned with the effect of brain hypoxia on cardiorespiratory control in the sleeping dog. Eleven unanesthetized dogs were studied; seven were prepared for vascular isolation and extracorporeal perfusion of the carotid body to assess the effects of systemic [and, therefore, central nervous system (CNS)] hypoxia (arterial PO(2) = 52, 45, and 38 Torr) in the presence of a normocapnic, normoxic, and normohydric carotid body during non-rapid eye movement sleep. A lack of ventilatory response to systemic boluses of sodium cyanide during carotid body perfusion demonstrated isolation of the perfused carotid body and lack of other significant peripheral chemosensitivity. Four additional dogs were carotid body denervated and exposed to whole body hypoxia for comparison. In the sleeping dog with an intact and perfused carotid body exposed to specific CNS hypoxia, we found the following. 1) CNS hypoxia for 5-25 min resulted in modest but significant hyperventilation and hypocapnia (minute ventilation increased 29 +/- 7% at arterial PO(2) = 38 Torr); carotid body-denervated dogs showed no ventilatory response to hypoxia. 2) The hyperventilation was caused by increased breathing frequency. 3) The hyperventilatory response developed rapidly (<30 s). 4) Most dogs maintained hyperventilation for up to 25 min of hypoxic exposure. 5) There were no significant changes in blood pressure or heart rate. We conclude that specific CNS hypoxia, in the presence of an intact carotid body maintained normoxic and normocapnic, does not depress and usually stimulates breathing during non-rapid eye movement sleep. The rapidity of the response suggests a chemoreflex meditated by hypoxia-sensitive respiratory-related neurons in the CNS.     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

Effect of inspiratory resistive loading on control of ventilation during progressive exercise

Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.     

Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans

Respiratory sinus arrhythmia (RSA) may be associated with improved efficiency of pulmonary gas exchange by matching ventilation to perfusion within each respiratory cycle. Respiration rate, tidal volume, minute ventilation (.VE), exhaled carbon dioxide (.VCO(2)), oxygen consumption (.VO(2)), and heart rate were measured in 10 healthy human volunteers during paced breathing to test the hypothesis that RSA contributes to pulmonary gas exchange efficiency. Cross-spectral analysis of heart rate and respiration was computed to calculate RSA and the coherence and phase between these variables. Pulmonary gas exchange efficiency was measured as the average ventilatory equivalent of CO(2) (.VE/.VCO(2)) and O(2) (.VE/.VO(2)). Across subjects and paced breathing periods, RSA was significantly associated with CO(2) (partial r = -0.53, P = 0.002) and O(2) (partial r = -0.49, P = 0.005) exchange efficiency after controlling for the effects of age, respiration rate, tidal volume, and average heart rate. Phase between heart rate and respiration was significantly associated with CO(2) exchange efficiency (partial r = 0.40, P = 0.03). These results are consistent with previous studies and further support the theory that RSA may improve the efficiency of pulmonary gas exchange.     

Digital Computer Simulation of Respiratory Response to Cerebrospinal Fluid PCO2 in the Cat

The respiratory control system is treated as linear with a transmission delay between ventilation and sensing points (chemoreceptors). To the accepted variables involving body gas stores, ventilatory effects, transmission effects, and steady state pH, P(CO2), P(O2) chemoreceptor response, certain detailed analysis of the central receptors have been added. By construction of a model for medullary CO(2) receptor utilizing expected values of CNS (central nervous system) circulation, CO(2) production, and tissue-buffering effects, results of experimental observation of the effects of alteration of CSF were simulated. The inclusion of CSF effects also allowed simulation of the response to alteration in inspired CO(2), hyperventilation, and the periodic breathing with prolongation of circulation time.     

Ventilatory and PaCO2 responses to voluntary and electrically induced leg exercise

We studied the role of central command mediation of exercise hyperpnea by comparing the ventilatory and arterial CO2 partial pressure (PaCO2) responses to voluntary (ExV) and electrically induced (ExE) muscle contractions in normal, awake human subjects. We hypothesized that if central command signals are critical to a normal ventilatory response, then ExE should cause a slower ventilatory response resulting in hypercapnia at the onset of exercise. ExE was induced through surface electrodes placed over the quadriceps and hamstring muscles. ExE and ExV produced leg extension (40/min) against a spring load that increased CO2 production (VCO2) 100-1,000 ml/min above resting level. PaCO2 and arterial pH during work transitions and in the steady state did not differ significantly from rest (P greater than 0.05) or between ExE and ExV. The temporal pattern of ventilation, tidal volume, breathing frequency, and inspired and expired times, and the ventilation-VCO2 relationship were similar between ExE and ExV. We conclude that since central command was reduced and/or eliminated by ExE, central command is not requisite for the precise matching of alveolar ventilation to increases in VCO2 during low-intensity muscle contractions.     

Gain of the ventilatory exercise stimulus: definition and meaning

The ratio G = delta VE/delta VCO2 where delta VA is change in ventilation and delta VCO2 is change in CO2 production, is often used to quantitate the ventilatory response to exercise and is the overall system gain (G). However, the actual variable of interest often is the gain for the exercise stimulus (GEX). Exercise stimulus refers to a stimulus or group of stimuli other than the mean levels of arterial PO2 (PaCO2), PCO2 (PaCO2), and pH (pHa) that act to increase ventilation during exercise. GEX will be equal to G only if the response to exercise is precisely isocapnic, normoxic, and without metabolic acidosis. A mathematical model was used to examine the relationship between G and GEX when 1) the response to exercise is not strictly isocapnic and 2) when the resting PaCO2 is shifted away from its normal value. It was found that 1) when the exercise response was not strictly isocapnic, G was a poor estimate of GEX and 2) when resting PaCO2 was changed while GEX wa assumed to remain constant, G was a function of the resting PaCO2. However, this dependence of G on resting PaCO2 is a system property that was caused by the nonlinear properties of the gas exchange processes and was not a fundamental property of the controller. It is concluded that G may not always be a good estimate of GEX and may lead to incorrect conclusions concerning the nature of the exercise stimulus.     

VCO2 and VE kinetics during moderate- and heavy-intensity exercise after acetazolamide administration.

The effect of carbonic anhydrase inhibition with acetazolamide (Acz) on CO2 output (VCO2) and ventilation (VE) kinetics was examined during moderate- and heavy-intensity exercise. Seven men [24 +/- 1 (SE) yr] performed cycling exercise during control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject performed step transitions (6 min) in work rate from 0 to 100 W [below ventilatory threshold (VET)]. VE and gas exchange were measured breath by breath. The time constant (tau) was determined for exercise VET by using a three-component model (fit from the start of exercise). VCO2 kinetics were slower in Acz (VET, MRT = 75 +/- 10 s) than Con (VET, MRT = 54 +/- 7 s). During VET kinetics were faster in Acz (MRT = 85 +/- 17 s) than Con (MRT = 106 +/- 16 s). Carbonic anhydrase inhibition slowed VCO2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise. The slowed VE kinetics in Acz during exercise 相似文献   

Mechanistic basis for the gas exchange threshold in Thoroughbred horses.

The exercising Thoroughbred horse (TB) is capable of exceptional cardiopulmonary performance. However, because the ventilatory equivalent for O2 (VE/VO2) does not increase above the gas exchange threshold (Tge), hypercapnia and hypoxemia accompany intense exercise in the TB compared with humans, in whom VE/VO2 increases during supra-Tge work, which both removes the CO2 produced by the HCO buffering of lactic acid and prevents arterial partial pressure of CO2 (PaCO2) from rising. We used breath-by-breath techniques to analyze the relationship between CO2 output (VCO2) and VO2 [V-slope lactate threshold (LT) estimation] during an incremental test to fatigue (7 to approximately 15 m/s; 1 m x s(-1) x min(-1)) in six TB. Peak blood lactate increased to 29.2 +/- 1.9 mM/l. However, as neither VE/VO2 nor VE/VCO2 increased, PaCO2 increased to 56.6 +/- 2.3 Torr at peak VO2 (VO2 max). Despite the presence of a relative hypoventilation (i.e., no increase in VE/VO2 or VE/VCO2), a distinct Tge was evidenced at 62.6 +/- 2.7% VO2 max. Tge occurred at a significantly higher (P < 0.05) percentage of VO2 max than the lactate (45.1 +/- 5.0%) or pH (47.4 +/- 6.6%) but not the bicarbonate (65.3 +/- 6.6%) threshold. In addition, PaCO2 was elevated significantly only at a workload > Tge. Thus, in marked contrast to healthy humans, pronounced V-slope (increase VCO2/VO2) behavior occurs in TB concomitant with elevated PaCO2 and without evidence of a ventilatory threshold.     

Is the hyperpnea of muscular contractions critically dependent on spinal afferents?

We studied the role of spinal afferent pathways in the hyperpnea of electrically induced muscle contractions (ExE). The ventilatory (VE) and arterial CO2 partial pressure (PaCO2) responses were measured at rest and during two levels of ExE in awake human paraplegic subjects with clinically complete lesions of the spinal cord (range T4-T11). We hypothesized that if peripheral neural drive is critical to a normal ventilatory response, then ExE in the absence of intact pathways should cause a lower ventilatory response resulting in hypercapnia at the onset of ExE. ExE was induced by stimulation of the quadriceps and hamstring muscles that approximately doubled the resting level of CO2 production (VCO2). PaCO2 during work transitions and in the latter stages of ExE did not differ significantly from that at rest. Arterial pH progressively declined over time during ExE (P less than 0.01) as a result of increased lactate concentration (P less than 0.01). The linear relationship between VE and VCO2 was similar to that found for normal human subjects during ExE (P = 0.73). These data suggest that VE and presumably alveolar ventilation (VA) can be appropriately matched to VCO2 during low-intensity muscle contractions of the lower extremities in the absence of intact spinal afferent pathways. Moreover, since it is unlikely that postulated "central command" mechanisms were initiated during ExE in these paraplegic subjects, the data provide support for our previous conclusion that central command is not obligatory for matching VA to VCO2 (J. Appl. Physiol. 64: 218-225, 1988).     

Relationship between hyperventilation and excessive CO2 output during recovery from repeated cycling sprints

The purpose of the present study was to examine whether excessive CO2 output (VCO2excess) is dominantly attributable to hyperventilation during the period of recovery from repeated cycling sprints. A series of four 10-sec cycling sprints with 30-sec passive recovery periods was performed two times. The first series and second series of cycle sprints (SCS) were followed by 360-sec passive recovery periods (first recovery and second recovery). Increases in blood lactate (DeltaLa) were 11.17+/-2.57 mM from rest to 5.5 min during first recovery and 2.07+/-1.23 mM from the start of the second SCS to 5.5 min during second recovery. CO2 output (VCO2) was significantly higher than O2 uptake (VO2) during both recovery periods. This difference was defined as VCO2excess. VCO2excess was significantly higher during first recovery than during second recovery. VCO2excess was added from rest to the end of first recovery and from the start of the second SCS to the end of second recovery (CO2excess). DeltaLa was significantly related to CO2excess (r=0.845). However, ventilation during first recovery was the same as that during second recovery. End-tidal CO2 pressure (PETCO2) significantly decreased from the resting level during the recovery periods, indicating hyperventilation. PETCO2 during first recovery was significantly higher than that during second recovery. It is concluded that VCO2excess is not simply determined by ventilation during recovery from repeated cycle sprints.     

Effects of previous exercise on the ventilatory determination of the aerobic threshold

To study the effects of previous submaximal exercise on the ventilatory determination of the Aerobic Threshold (AeT), 16 men were subjected to three maximal exercise tests (standard test = ST, retest = RT, and test with previous exercise = TPE ) on a cycle ergometer. The protocol for the three tests consisted of 3 min pedalling against 25 W, followed by increments of 25 W every minute until volitional fatigue. TPE was preceded by 10 min cycling at a power output corresponding to the AeT as determined in ST, followed by a recovery period pedalling against 25 W until VO2 returned to values consistent with the initial VO2 response to 25 W. AeT was determined from the gas exchange curves (ventilatory equivalent for O2, fraction of expired O2, excess of VCO2, ventilation, and respiratory gas exchange ratio) printed every 30 s. The results showed good ST X RT reliability (r = 0.89). TPE showed significantly higher AeT values (2.548 +/- 0.44 1 X min-1) when compared with ST (2.049 +/- 0.331 X min-1) and RT (2.083 +/- 0.30 1 X min-1). There were no significant differences for the sub-threshold respiratory gas exchange ratios among the trials. The sub-threshold VO2 response showed significantly higher values for TPE at power outputs above 50 W. It was concluded that the performance of previous exercise can increase the value for the ventilatory determination of the AeT due to a faster sub-threshold VO2 response.     

Background ventilatory stimulus as a determinant of load compensation

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment.     

CO2 elimination as a function of frequency and tidal volume in rabbits during HFO

CO2 elimination (VCO2) was monitored during high-frequency oscillation (HFO) over a frequency (f) range of 2-30 Hz in anesthetized and paralyzed rabbits to determine whether effective gas exchange could be achieved in this species, to determine the f and tidal volume (VT) dependence of gas exchange in this species, and to compare these results with those from dog and human studies. We were able to produce VCO2 levels during HFO that exceeded normal steady-state levels of CO2 production with VT's less than the total dead space volume. VCO2 was related to f in a curvilinear fashion, whereas in some rabbits VCO2 became independent of f at higher frequencies. This curvilinear relationship between f and VCO2 is similar to data from humans but contrasts with the linear relationship found in dogs. Evidence is presented indicating frequency-dependent behavior of gas exchange is correlated with a frequency-dependent decrease in respiratory system resistance. We propose that the frequency-dependent mechanical properties of the rabbit lung may also account for the species differences in HFO gas exchange.     

Chronic hypoxia enhances the phrenic nerve response to arterial chemoreceptor stimulation in anesthetized rats.

Chronic exposure to hypoxia results in a time-dependent increase in ventilation called ventilatory acclimatization to hypoxia. Increased O(2) sensitivity of arterial chemoreceptors contributes to ventilatory acclimatization to hypoxia, but other mechanisms have also been hypothesized. We designed this experiment to determine whether central nervous system processing of peripheral chemoreceptor input is affected by chronic hypoxic exposure. The carotid sinus nerve was stimulated supramaximally at different frequencies (0.5-20 Hz, 0.2-ms duration) during recording of phrenic nerve activity in two groups of anesthetized, ventilated, vagotomized rats. In the chronically hypoxic group (7 days at 80 Torr inspired PO(2)), phrenic burst frequency (f(R), bursts/min) was significantly higher than in the normoxic control group with carotid sinus nerve stimulation frequencies >5 Hz. In the chronically hypoxic group, peak amplitude of integrated phrenic nerve activity ( integral Phr, percent baseline) or change in integral Phr was significantly greater at stimulation frequencies between 5 and 17 Hz, and minute phrenic activity ( integral Phr x f(R)) was significantly greater at stimulation frequencies >5 Hz. These experiments show that chronic hypoxia facilitates the translation of arterial chemoreceptor afferent input to ventilatory efferent output through a mechanism in the central nervous system.     

Analysis of abnormalities of capillary CO2 exchange in vivo

Capillary CO2 exchange in vivo is affected by several interdependent reactions and transport processes. A mathematical model that includes all the significant chemical and transport events that are presumed to occur during capillary gas exchange has been used to investigate the effect of inhibition of 1) erythrocyte HCO(3-)-Cl- exchange, 2) lung carbonic anhydrase (CA) activity with access to plasma, and 3) erythrocyte CA activity on overall pulmonary CO2 excretion (VCO2) during rest and moderate exercise. Any decrement in VCO2 due to inhibition of HCO(3-)-Cl- exchange and/or CA activity, should result in compensatory alterations in cardiac output and/or an increase in the mixed venous blood-to-alveolar PCO2 gradient [(delta PCO2)V-A] to restore steady-state VCO2. Our computations show that complete inhibition of erythrocyte anion exchange would require a compensatory increment in cardiac output of approximately 30-40% or an increase in (delta PCO2)V-A from 6 to 8.3 Torr at rest and from 12 to 15.6 Torr during moderate exercise, if lung CA activity is intact. In the absence of availability of lung CA activity to plasma, the necessary (delta PCO2)V-A is 10.5 Torr at rest and 19.5 Torr during moderate exercise. Complete inhibition of lung and erythrocyte CA activity is predicted to require (delta PCO2)V-A of 39.1 Torr at rest and 74.2 Torr during moderate exercise. These results suggest that HCO(3-)-Cl- exchange might not be vital to maintenance of CO2 transfer and perhaps has a more important role in minimizing the changes in plasma pH associated with microvascular gas exchange in vivo.     

Relation between the change of slope of heart rate and second lactic and ventilatory thresholds in muscular exercise with large load]

The time-course of heart rate, blood lactate, and ventilatory gas exchange was studied during an incremental exercise test on cycloergometer in order to ascertain whether heart rate deflection occurred at the same load as the second lactate S[La]2) and ventilatory (SV2) thresholds. Twelve moderately trained subjects, 22 to 30 years old, participated in the study. The initial power setting was 30 W for 3 min with successive increases of 30 W every min except at the end of the test where the increase was reduced to 20 and 10 W.min-1. Ventilatory flow (VE), oxygen uptake (VO2), carbon dioxide production (VCO2, ventilatory equivalents of O2 (EO2 = VE/VO2) and CO2 (ECO2 = VE/VCO2), and heart rate (HR) were determined during the last 20 s of every min. Venous blood samples were drawn at the end of each stage of effort and analyzed enzymatically for lactate concentration ([La]). The HR deflection, S[La]2, and SV2 were represented graphically by two investigators using a double blind procedure. Following the method proposed by Conconi et al. 1982, the deflection in HR was considered to begin at the point beyond which the increase in work intensity exceeded the increase in HR and the linearity of the work rate/HR relationship was lost. S[La]2 corresponded to the second breaking point of the lactate time-course curve (onset of blood lactate accumulation) and SV2 was identified at the second breaking point in the increase in VE and ventilatory equivalent for O2 uptake accompanied by a concomitant increase in ventilatory equivalent for CO2 output. We observed that the deflection point in HR was present only in 7 subjects. The work load, VO2, HR, and [La] levels at which heart rate departed from linearity did not differ significantly from those determined with S[La]2 ans SV2. The VO2 and HR values at HR deflection point were significantly correlated with those measured at S[La]2 and SV2. It is concluded that deflection in heart rate does not always occur, and when it does, it coincides with the second lactate and ventilatory gas exchange thresholds. It can thus be used for the determination of optimal intensity for individualized aerobic training.