Use of Acetylene Breathing to Determine Cardiac Output in... : Medicine & Science in Sports & Exercise (original) (raw)
Cardiac output (𝑄̇C) is a major determinant of arterial blood pressure and maximal oxygen uptake (V̇O2max) (3). Because of its clinical and physiological importance, accurate and reproducible measurement of 𝑄̇C has been and continues to be of great interest to clinical researchers. Historically, the direct Fick and dye-dilution techniques have been considered “gold-standard” measures of 𝑄̇C (29). However, due to their highly invasive nature, requirement of substantial medical support, and questionable appropriateness for common use in special populations (e.g., the elderly), these techniques are not practical for use in the majority of exercise physiology and clinical research laboratories.
Based on these limitations, several alternative techniques have been developed to assess 𝑄̇C noninvasively. One such technique is the closed-circuit soluble gas rebreathing technique. The popularity of this technique has been based in large part on its ability to provide measurements of 𝑄̇C during heavy submaximal and maximal exercise (13,18,19,24,28,31). However, this technique has several potentially important practical limitations that have previously been described (29); for example, the nonphysiological nature of the rebreathing procedure may increase arterial PCO2 and cause dyspnea, and during resting conditions the hyperventilation required to perform the procedure may artificially increase 𝑄̇C. As a consequence, recently non-rebreathing variations of the soluble gas technique have been developed that provide estimates of 𝑄̇C comparable with the direct Fick procedure (2,16), at least in healthy young adults. Data pertaining to a comparison of the estimates of 𝑄̇C during exercise from open-circuit acetylene breathing to those generated by the rebreathing technique have been presented in preliminary format only (6). Moreover, the day-to-day reproducibility of the open-circuit procedure has not been established. Finally, it is unknown as to whether the open-circuit technique provides comparable estimates of 𝑄̇C to estimates made using the closed-circuit acetylene rebreathing technique during exercise in older adults. Given recent increased interest in the study of exercise and human aging, the absence of data on older adults is a significant limitation in the use of the open-circuit acetylene breathing technique.
Accordingly, the purpose of this investigation was to establish the reproducibility of open-circuit acetylene breathing for measuring 𝑄̇C during submaximal and near-maximal (>95% peak heart rate) exercise in young and older adults, as well as its comparability against the previously established closed-circuit acetylene rebreathing technique. We hypothesized that during submaximal to near-maximal exercise in both young and older adults, open-circuit acetylene breathing would provide: 1) reproducible estimates of 𝑄̇C, and 2) similar absolute values of 𝑄̇C to those obtained using closed-circuit acetylene rebreathing.
METHODS
Subjects.
Twenty adults, 10 young (28 ± 1 yr, 72.2 ± 1.7 kg (mean ± SE)) and 10 older (61 ± 1 yr, 79.6 ± 3.2 kg) men, were studied. All participants were healthy as assessed by medical history. In addition, older participants underwent a physical examination with resting ECG as well as ECG and blood pressure assessment during incremental cycle ergometry exercise to exhaustion. Participants were nonsmokers and were not taking any regular medications. The nature, purpose, and risks of the study were explained to each participant before written informed consent was obtained. The Human Research Committee at the University of Colorado at Boulder approved the experimental protocol.
Experimental procedures.
Participants reported to the laboratory on four separate occasions. During the first visit participants performed incremental cycle ergometer exercise (young adults: 25 W·min−1; older adults: 15 W·min−1) until exhaustion to determine V̇O2peak. During each of the three subsequent visits, participants performed repeated cycle-ergometry exercise at four different exercise intensities (low-, moderate-, heavy- and near-maximal intensity; young adults: 70, 140, 210 W, and near-maximal intensity: >95% HRpeak; older adults: 35, 70, 140 W, and near-maximal intensity: >95% HRpeak). The order of the exercise intensities was always the same. Low-, moderate-, and heavy-intensities lasted approximately 10–12 min (the time required to attain steady state plus three repeat sets of measurements). Brief rest periods (< 2 min) were permitted between incremental stages; however, these were rarely taken. Near-maximal-intensity exercise was performed twice during each visit separated by a brief recovery period of approximately 5 min. Each near-maximal-intensity bout lasted 2–5 min, and measurements were made when participants reported that they could continue exercising for only 30 more seconds. Visits were separated by a period of time not less than 2 d. 𝑄̇C was estimated using open-circuit acetylene breathing during two of these visits and using closed-circuit acetylene rebreathing during the other visit. The order of visits was randomized. Heart rate was determined via radio telemetry (Polar heart rate monitor, Polar Electro, Kempele, Finland) and V̇O2 via indirect calorimetry using a mixing chamber technique (respiratory mass spectrometer: Perkin Elmer MGA-1100, Norwalk, CT; pneumotachograph: Hans Rudolph, Series 3813, Kansas City, MO).
Open-circuit acetylene breathing.
𝑄̇C was estimated using open-circuit acetylene breathing as previously described (OpCirc2 (16)). Once exercise steady state had been attained, during an expiration, inspired gas was switched from room air to the open-circuit gas mixture (0.5% C2H2, 21% O2, 5% He, balance N2) by way of a pneumatic switching valve (Hans Rudolph, PO271, controller 4285A) connected to a non-rebreathing T-valve (Hans Rudolph, 2700). Participants inspired the open-circuit gas mixture from a large reservoir for 10–12 breaths and were then switched back to room air. A wash-out period of 1–2 min separated each data collection. This wash-out period was sufficient to reduce end-tidal acetylene concentration to <10% of the reservoir values. The algorithms for calculating 𝑄̇C used the end-tidal acetylene concentration of the breath preceding wash-in as “back-pressure” for alveolar uptake of acetylene. Expired gases were sampled continuously using a respiratory mass spectrometer (Perkin Elmer, MGA1100) with a phase delay of 0.50 s. Inspired and expired gas volumes were measured using a pneumotachograph (Hans Rudolph). 𝑄̇C was calculated using a finite difference modeling technique where the change in acetylene volume in the alveolar compartment per unit time is equal to the rate of disappearance into the blood plus the amount entering the alveolar volume by inspiring via the anatomical dead space. This modeling technique has been previously described (OpCirc2 (16)).
Closed-circuit acetylene rebreathing.
𝑄̇C was estimated using closed-circuit acetylene rebreathing as previously described (15). Once steady state had been attained, at end expiration, the inspired gas was switched from room air to the closed-circuit gas mixture (0.5% C2H2, 45% O2, 5% He, balance N2) by way of a pneumatic switching valve (Hans Rudolph, 8200 Series) connected to a non-rebreathing T-valve. Participants inspired the closed-circuit gas mixture from a 5-L rebreathing bag (Hans Rudolph, Model 6046) for seven to eight breaths and were then switched back to room air. Rebreathe gas volume was estimated from measured tidal volume during the determination of V̇O2 at the same exercise intensity. Participants were instructed to empty the rebreathe bag with each inspiration. A wash-out period of 1–2 min separated each data collection. This wash-out period was sufficient to reduce end-tidal acetylene concentration to <10% of the reservoir values. The algorithms for calculating 𝑄̇C used the end-tidal acetylene concentration of the breath preceding wash-in as “back-pressure” for alveolar uptake of acetylene. Inspired and expired gases were sampled continuously using a respiratory mass spectrometer with a phase delay of 0.50 s. Gas volumes were measured using a bidirectional turbine (Ventilation Measurement Module, VMM2 Series, Laguna Niguel, CA). 𝑄̇C was calculated using established algorithms (27).
Data analysis.
Three measurements of 𝑄̇C were made at each exercise intensity with the exception of near-maximal intensity where only two measurements were made. 𝑄̇C was then calculated as the mean of the two or three measures.
All data are expressed as mean ± SE unless otherwise indicated. To gain insight into potential systematic bias between daily tests, a two-way repeated measures ANOVA was used to compare estimates of 𝑄̇C from open-circuit acetylene breathing on day 1 and day 2. Two-way repeated measures ANOVA was also used to determine any significant differences in 𝑄̇C estimated by the different techniques. Significance was accepted as P < 0.05.
Day-to-day reproducibility of estimates of 𝑄̇C by open-circuit acetylene breathing and agreement between estimates of 𝑄̇C by open-circuit acetylene breathing (day 1) and close-circuit acetylene rebreathing was assessed using established techniques (1,5,14). Agreement (bias) was expressed as the mean of the differences obtained between the different techniques and days. The limits of agreement were expressed as the mean ± 2 SD; the 95% confidence intervals of the bias as well as the lower and upper limits of agreement were calculated as previously described (5). All comparisons between open-circuit acetylene breathing and closed-circuit acetylene rebreathing were based on data collected during the first day of open-circuit testing. This was chosen prospectively.
RESULTS
Incremental and repeated cycle ergometry.
Peak responses to incremental cycle ergometry are presented in Table 1. V̇O2peak, peak heart rate (HRpeak) and peak work rate (WRpeak) were greater (P < 0.05) in young compared with older adults. Peak respiratory exchange ratio (RER) was not different (_P_ > 0.05) between young and older adults, indicating that both groups exerted similar maximal effort. Data collected during repeated cycle ergometry exercise are presented in Table 2. At the same absolute work rate V̇O2 was not different (P > 0.05) between young and older adults, whereas %V̇O2peak and HR were lower (P < 0.05) in the young adults. Near maximal-intensity exercise elicited similar %HRpeak (P < 0.05) between young and older adults, but a greater absolute HR (P = 0.01) in the young adults.
Incremental cycle ergometry data.
Repeated cycle-ergometry data.
Reproducibility of open-circuit acetylene breathing.
The relations of estimates and limits of agreement of 𝑄̇C, between visits by open-circuit acetylene breathing in young and older adults are displayed in Figure 1. Estimates of 𝑄̇C were reproducible: 1) estimates of 𝑄̇C were not different (P > 0.05) at each exercise intensity when compared between visits for both young and older adults, supporting the absence of a potential systematic bias between daily tests; 2) the standard error of measurement (SEM), the degree to which repeated measurements vary for individuals (1), was 1.52 L·min−1 (young adults) and 0.94 L·min−1 (older adults); 3) the bias and limits of agreement were 0.2 ± 4.2 L·min−1 (young adults) and 0.1 ± 2.8 L·min−1 (older adults); 4) to assist in comparing SEM between young and older adults, we have expressed the within group variability as the coefficient of variation (CV); these were 6–8% (young adults) and 4–10% (older adults) with the greatest variability observed for both age-groups during lower-intensity exercise, and the least variability at the near-maximal exercise intensity. The within-session CV for a given work intensity was 2.0–4.0% (young adults) and 2.2–4.1% (older adults); and 5) test-retest correlations were young adults: r = 0.90, P < 0.001, r2 = 0.82; older adults: r = 0.91, P < 0.001, r2 = 0.82.
Reproducibility of estimates of cardiac output as estimated by open-circuit acetylene breathing in young and older adults. Young adults are represented by closed circles and older adults by open circles. A, Solid line represents line of identity (x = y). Young adults: r = 0.90, P < 0.001; day 2 = (0.9 × day 1) + 2.4, r2 = 0.82. Older adults: r = 0.91, P < 0.001; day 2 = (1.0 × day 1) + 0, r2 = 0.82. B and C, Bland-Altman plots of cardiac output as estimated by open-circuit acetylene breathing on two separate days in young (B) and older (C) adults.
Open-circuit versus closed-circuit.
The relation of estimates and limits of agreement of 𝑄̇C by open-circuit acetylene breathing (day 1) and closed-circuit acetylene rebreathing in young and older adults are displayed in Figure 2. Estimates of 𝑄̇C were comparable between the two techniques: 1) estimates of 𝑄̇C at each exercise intensity were not different (P > 0.05) for both techniques in young and older adults; 2) SEM = 1.52 L·min−1 (young adults) and 1.13 L·min−1 (older adults); 3) the bias and limits of agreement were 0.9 ± 4.4 L·min−1 (young adults) and 0.1 ± 3.2 L·min−1 (older adults); 4) CV between the techniques was 5–10% (young adults) and 5–9% (older adults); and 5) correlations between techniques were young adults: r = 0.89, P < 0.001, r2 = 0.79; older adults: r = 0.88, P < 0.001, r2 = 0.78.
Relation between cardiac output as estimated by closed-circuit acetylene rebreathing and open-circuit acetylene breathing in young and older adults. Young adults are represented by closed circles and older adults by open circles. A, Solid line represents line of identity (x = y). Young adults: r = 0.89, P < 0.001; open-circuit = (1.0 × closed-circuit) + 1.5, r2 = 0.79. Older adults: r = 0.88, P < 0.001; open-circuit = (0.9 × closed-circuit) + 1.6, r2 = 0.78. B and C, Bland-Altman plots of cardiac output as estimated by closed-circuit acetylene rebreathing and open-circuit acetylene breathing in young (B) and older (C) adults.
Relation between 𝑄̇C and V̇.
The relations between V̇O2 and 𝑄̇C as determined by open-circuit acetylene breathing and closed-circuit acetylene rebreathing in young and older adults are displayed in Figure 3. The slopes of the relation between V̇O2 and 𝑄̇C were similar when 𝑄̇C was estimated by open-circuit acetylene breathing and closed-circuit acetylene rebreathing and were not different between young and older adults. At the same absolute work rate (70 and 140 W), and hence similar V̇O2, 𝑄̇C was greater in young adults compared with older adults whether estimated by open-circuit acetylene breathing or closed-circuit acetylene rebreathing (see Table 2, all comparisons P < 0.01).
Relation between cardiac output and oxygen uptake in young and older adults. Young adults are represented by closed circles and older adults by open circles. A, Cardiac output estimated by open-circuit acetylene breathing. Young adults: r = 0.86, P < 0.001; cardiac output = (4.4 × V̇O2) + 7.8, r2 = 0.75. Older adults: r = 0.87, P < 0.001; Cardiac output = (4.4 × V̇O2) + 4.8, r2 = 0.75. B, Cardiac output estimated by closed-circuit acetylene rebreathing. Young adults: r = 0.85, P < 0.001; cardiac output = (4.4 × V̇O2) + 7.2, r2 = 0.72. Older adults: r = 0.90, P < 0.001; cardiac output = (4.9 × V̇O2) + 4.4, r2 = 0.81.
DISCUSSION
There are several new and important findings from the present study. First, we have shown for the first time that the open-circuit acetylene breathing technique provides reproducible measurements of 𝑄̇C during large-muscle dynamic exercise. Second, the reproducibility of the technique was established in both young and older participants. Third, the between-session reproducibility of the procedure is greatest at near maximal exercise intensities (>95% HRpeak). Fourth, the open circuit acetylene breathing technique may be confidently used to estimate 𝑄̇C during exercise in place of the traditional, but practically problematic, acetylene rebreathing procedure. As such, the present results complement and significantly extend previous findings (2,16), demonstrating the reproducibility and utility of use in different populations for the open-circuit acetylene breathing technique for measuring 𝑄̇C during exercise in human participants.
The use of the open-circuit acetylene breathing technique to estimate 𝑄̇C is based on several assumptions that have previously been described (2,16). The underlying conceptual model for both open- and closed-circuit techniques is that of a single alveolar gas compartment connected to the rebreathe or inhaled gas reservoir by an anatomical dead space. Acetylene uptake (the rate of alveolar-capillary transfer) occurs in proportion to the blood flow to the compartment (equal to 𝑄̇C in healthy adults), but the rate of change in gas concentration is inversely proportional to the alveolar gas volume. Although both the closed- and open-circuit methods involve uptake of a soluble gas by pulmonary circulation, the underlying mathematics and methods are quite different. For closed-circuit, the underlying model is one of two compartments separated by a dead space. The two compartments are well ventilated and disappearance of the soluble gas from the system obeys single exponential kinetics. Thus, cardiac output and tissue volume are derived from semilog plots of acetylene disappearance compared with helium equilibration (27). For open-circuit, although the underlying model is similar, that of a well-mixed gas exchanging region and dead space, there is no equilibration with a rebreathe bag. The mathematics describe the uptake of the soluble and insoluble gas with each breath, and more involved mass balance equations are solved to derive cardiac output. The popularity of closed-circuit acetylene rebreathing has been based in large part on its ability to provide measurements of 𝑄̇C during heavy submaximal and maximal exercise by noninvasive means. Our data demonstrate that the open-circuit acetylene breathing technique performs very well in these exercise domains for both young and older adults. Indeed, from a reproducibility standpoint, the variability in measures of 𝑄̇C was lowest at near-maximal intensity. Previous studies have shown that older adults have wider distribution of ventilation to perfusion ratios compared with young adults (7,10). As such, one might expect the open-circuit to provide less accurate and/or reliable estimates of 𝑄̇C in older adults. In the present investigation, however, we have demonstrated that this is not the case. Indeed, in a group of healthy older adults excellent reproducibility from open-circuit acetylene breathing (test-retest r2 = 0.82) and very good comparability with closed-circuit acetylene rebreathing (r2 = 0.78) was observed. The limits of agreement between the open-circuit acetylene breathing and the closed-circuit acetylene rebreathing for the young and older suggest the potential for individual differences between methods. However, these are small in comparison with the variability that may be encountered with closed-circuit rebreathing in naïve subjects (22).
Although not an experimental aim of the present investigation, because we found that values for 𝑄̇C at the same V̇O2 were lower in the older compared with the young adults, this may be deserving of brief comment here. The influence of age on 𝑄̇C at a given submaximal work rate is unclear. Several studies have shown that compared with young adults, 𝑄̇C at the same absolute work rate was lower in older adults (8,11,20,26), whereas others have shown no age-related differences (4,21,23). Regardless, it is clear that there is no influence of age on the slope of the relation between 𝑄̇C and V̇O2 during progressive exercise (8,11,23,25). In the present study, we have shown that when young and older adults performed cycle exercise at the same absolute work rate, 𝑄̇C was greater in young adults but the 𝑄̇C/V̇O2 slope was unaffected by age. Our derived value for the slope of the 𝑄̇C/V̇O2 relation (4.4) illustrates this point as it compares well with values reported in previous literature (range: 4.1–5.5) derived from a variety of techniques including acetylene breathing and dye dilution (12,23,24). A potential experimental limitation associated with our observation of age-related differences in 𝑄̇C pertains to the difference in the relative fitness of our young and older participants: according to recent ACSM guidelines (9) the aerobic fitness of the young participants may be described as “well above average” whereas the older adults would only be “average.” Thus, the relatively lower level of aerobic fitness of the older adults may have contributed to the difference in 𝑄̇C at a given submaximal work rate.
Although the closed-circuit acetylene rebreathing technique has been widely used and repeatedly validated (15,17,24,27), there are several advantages of open-circuit acetylene breathing over closed-circuit acetylene rebreathing to determine 𝑄̇C (2,16,30). These advantages include: 1) increased comfort of the participant, and hence tolerance of the procedure as spontaneous breathing during data collection is allowed; and 2) the procedure is simple to perform for both the participant and the experimenter. Additionally, the experimenter has greater confidence as to the timing of manual switching between inspired room air and the acetylene mixtures (anytime during an expiration versus exactly at the end of an expiration, respectively). Disadvantages of the closed-circuit acetylene rebreathe technique include: 1) the difficulty associated with accurate prediction of rebreathe gas volume compared with actual tidal volume, 2) the concentration of carbon dioxide in the rebreathe mixture will increase as the test progresses, and 3) the increase in carbon dioxide also will reduce the volume of the rebreathe mixture toward the end of the procedure as RER increases. In recent years, several modifications have been described to improve the closed-circuit acetylene rebreathe technique (24,29), including removal of helium from the rebreathe mixture and having participants exhale to residual volume before rebreathing, thus eliminating the need to estimate the exact volume of gas required. However, even with these modifications, when all of the issues are considered, then the decision between open-circuit acetylene breathing and closed-circuit acetylene rebreathing to measure 𝑄̇C should favor the open-circuit technique. Indeed, use of open-circuit non-rebreathing techniques for the determination of 𝑄̇C has been described as “a major advancement for exercise physiology laboratories” (6). In the present study, we have shown that investigators who currently use closed-circuit acetylene rebreathing can confidently change to open-circuit acetylene breathing, including investigators that study healthy older adults.
In summary, we have extended previous research by demonstrating that in both healthy young and older adults, open-circuit acetylene breathing provides reproducible estimates of 𝑄̇C that are comparable to estimates obtained from the widely used closed-circuit acetylene rebreathing technique.
This research was supported by NIH awards AG06537 and AG13038, and American Heart Association 99020445Z.
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Keywords:
OPEN-CIRCUIT ACETYLENE BREATHING; CLOSED-CIRCUIT ACETYLENE REBREATHING; AGING; OXYGEN UPTAKE; EXERCISE
©2003The American College of Sports Medicine