High-intensity intermittent exercise (HIIE) is characterized by repeated bouts of vigorous activity, interspersed by recovery phases of rest or low-intensity exercise. Due to these recovery phases, high peak workloads can be sustained for a longer accumulated time in HIIE than in one bout of continuous exercise (CE) (Gibala et al., 2012; Saltin et al., 1976).

“Aerobic” HIIE has been shown to induce similar or even superior physiological effects on oxidative capacity and endurance performance compared to traditional moderate-intensity CE in both healthy individuals (Billat, 2001; Daussin et al., 2007, 2008; Helgerud et al., 2007) and patients with chronic disease (Iellamo et al., 2013; Kemi and Wisloff, 2010; Meyer et al., 1997; Smart et al., 2013; Wisloff et al., 2007). With respect to the lactate shuttle theory (Brooks, 1986; 2009), we propose that exercise may be called “aerobic” if it provokes a systemic steady state in blood lactate concentration (LaSS) which means a balance of lactate production and elimination (Hofmann and Tschakert, 2011). In addition, even sprint intervals including short bouts of “all out” exercise for only a few seconds have been reported to enhance maximum oxygen uptake (VO_2max) primarily due to peripheral muscular adaptations induced by maximal workloads (Burgomaster et al., 2008; Gibala et al., 2006; 2012; Hawley, 2008).

A large part of HIIE studies referred to in literature investigated training adaptations such as improvements in VO_2max, whereas investigations of an acute physiological response to interval exercise are rare. However, depending on the setting of single determinants of HIIE (peak workload (P_peak), peak workload duration (t_peak), recovery load (P_rec), recovery duration (t_rec), mean load (P_mean), and numbers of intervals) (Buchheit and Laursen, 2013a; 2013b; Gibala et al., 2012; Tschakert and Hofmann, 2013), a broad spectrum of acute metabolic and cardiorespiratory responses can be generated by HIIE (Billat, 2001). The acute physiological response strongly determines the particular muscular and systemic training adaptations (Hawley, 2004; 2008) as well as the potential health risks during exercise, particularly in diseased populations (Meyer et al., 1997; 1998; Keteyian, 2012; Rognmo et al., 2012).

A HIIE model that has been successfully adopted in training intervention studies in both healthy individuals (Helgerud et al., 2007) and patients suffering from different chronic diseases such as heart failure (Wisloff et al., 2007) is the 4 x 4 min regime (t_peak = 4 min; P_peak = 85-95 % of maximum heart rate (HR_max); t_rec = 3 min; P_rec = 50-70 %HR_max). This HIIE model has frequently been called “aerobic” (Helgerud et al., 2007; Rognmo et al., 2004; Tjonna et al., 2008; Wisloff et al., 2007); however, the acute physiological response induced by 4 x 4 HIIE has not yet been described.

There is still a lack of knowledge regarding the detailed acute metabolic and cardiorespiratory response to particular HIIE modes and the heterogeneity of this response due to different interval settings (Gibala et al., 2012). In addition, the regulation and predictability of desired acute physiological responses before HIIE remain poorly understood. The acute response to continuous exercise is predictable and controllable by setting the intensity and duration. Analogously, the acute physiological response induced by a particular intermittent exercise regime should also be controllable by means of a prescription using the aforementioned HIIE determinants. This is of high relevance particularly if HIIE is applied in training intervention studies in healthy and, more importantly, in diseased individuals. A consistent HIIE prescription model that enables the regulation and prediction of acute physiological responses to HIIE hence is needed (Tschakert and Hofmann, 2013).

The acute physiological response to interval exercise is to a large extent influenced by P_mean that can be calculated using the equation P_mean = (P_peak · t_peak + P_rec · t_rec) / (t_peak + t_rec) (equation 1). We recommended setting P_mean purposefully as a separate determinant since the mean load determines the acute mean cardiorespiratory response and additionally has a crucial impact on the acute metabolic response (Tschakert and Hofmann, 2013).

However, t_peak and P_peak also strongly influence the acute metabolic and peak cardiorespiratory response as emphasized by Astrand et al. (1960) and Saltin et al. (1976) decades ago. They found that HIIE with a long t_peak yielded higher acute metabolic and peak cardiorespiratory responses (no LaSS, greater oscillation of HR and VO₂ values around the respective mean values) compared to HIIE with a short t_peak. However, the authors did not further explore the relevance of P_mean or regulation of the acute response to HIIE.

“Aerobic” HIIE (interval exercise that leads to a LaSS) can be sustained for a longer total duration than HIIE that induces a rising blood lactate accumulation. Therefore, the question arises if the acute physiological response to interval exercise can be controlled and predicted using P_mean and, in particular, if HIIE is “aerobic” provided P_mean is set below the second lactate turn point (LTP₂) determined in an incremental exercise test (IET), the upper limit to generate “aerobic” constant load exercise (Hofmann et al., 1997; 2005).

The purpose of the present study was to determine the acute cardiorespiratory and metabolic response produced by long (t_peak = 4 min) and short (t_peak = 20 s) HIIE compared to CE matched for mean load and exercise duration in young healthy subjects. We aimed to determine which HIIE regime is “aerobic” and, in general, allows a regulation and predictability of the acute physiological response using P_mean according to equation 1. For this purpose the acute physiological responses to CE were used as reference values.

We hypothesized that there would be no significant difference in the acute metabolic and peak cardiorespiratory response between short HIIE and CE. However, long HIIE was hypothesized to yield a significantly higher acute physiological response than CE and short HIIE. As a consequence, we hypothesized that the regulation and prediction of the acute metabolic and peak cardiorespiratory response during HIIE using P_mean is possible in short rather than in long intervals and that short HIIE but not long HIIE is “aerobic”. These working hypotheses were proposed despite the fact that P_peak in short HIIE was considerably higher compared to long HIIE and CE.

Six young healthy well-trained sport students (5 males, 1 female; age: 25.7 ± 3.1 years; height: 1.80 ± 0.04 m; weight: 76.7 ± 6.4 kg; VO_2max: 4.33 ± 0.7 l·min^-1) participated in this study. The experimental protocol was approved by the institutional ethical review committee. Once the test design, the experimental procedures, and associated risks had been explained, all subjects gave their written informed consent before participating in this study. They were familiar with the cycle ergometer exercise in our laboratory and were instructed to avoid strenuous exercise 24 hours before each testing session.

All subjects were required to report to the laboratory on four occasions separated by at least two days, and on each occasion the participants completed an exercise test conducted on an electronically controlled and mechanically braked cycle ergometer (Monark Ergomedic 839E, Monark, Sweden).

On their first visit, subjects performed an incremental exercise test (IET) until exhaustion in order to assess VO_2max, HR_max, and maximum aerobic power output (P_max). In addition, the first and second turn points for lactate (LTP₁, LTP₂) and for ventilation (VT₁, VT₂) were determined referring to the three phase model of metabolism (Hofmann and Tschakert, 2011) and to the Lactate Shuttle Theory by Brooks (1986; 2009). Subsequently, the participants performed three different exercise sessions matched for mean load and exercise duration in randomized order: 1) a modified version of the original Norwegian 4 x 4 HIIE model (Helgerud et al., 2007) with a t_peak of 4 min (long HIIE); 2) high-intensity interval exercise with a t_peak of 20 s (short HIIE); and 3) continuous exercise (CE) with a target workload equating to P_mean of both HIIE tests. The duration of each specific exercise session (without resting periods, warm up, and cool down) was 28 minutes. The participants were permitted to cycle at a cadence of 70 - 90 rpm, and each subject completed all tests with the same rpm.

At the beginning of IET, subjects sat quietly on the cycle ergometer for 3 min (0 W). After this initial rest period, they completed a 3 min warm-up at 40 W for males and 20 W for the female, respectively. Then, the workload was increased by 20 W (for males) and 15 W (for female), respectively, every minute until volitional exhaustion occurred according to the standard protocol of the Austrian Society of Cardiology (Wonisch et al., 2008). In the following 3 min recovery period, the same workload as during warm-up was applied, and finally the participants had to rest for 3 min again sitting quietly on the cycle ergometer (0 W). Maximal (P_max, HR_max) and submaximal markers (LTP₁, LTP₂) were determined in order to prescribe exercise intensities of the following specific continuous and interval-type exercise tests.

All subjects were required to perform three specific exercise sessions (long HIIE, short HIIE, and CE) matched for mean load and exercise duration in randomized order. In total, each test lasted about 47 min. It started with a 3 min resting period (sitting quietly on the cycle ergometer, 0 W), followed by a 10 min warm-up phase consisting of 3 min cycling at 40 W (males) and 20 W (female), respectively, and a 7 min adaptation phase with a workload just below the individual P_LTP1. This 3 + 7 min warm-up phase was conducted in order to minimize day-to-day variations in exercise performance and to prepare for the high peak workloads in HIIE. Subsequently, the specific CE or HIIE protocol of about 28 min started. Finally, a 3 min active recovery with 40 W (males) and 20 W (female), respectively, and 3 min passive recovery (0 W) on the cycle ergometer concluded the IET.

According to Helgerud et al. (2007), long HIIE in our study consisted of four intervals (4 x (4+3) min). The work periods of 4 min (t_peak) were performed at a P_peak corresponding to the power output at 95 % of HR_max from IET, and the recovery phases (t_rec) of 3 min were performed at a P_rec corresponding to the power output at 70 % of HR_max from IET. P_mean was calculated using the following equation: P_mean = (P_peak · t_peak + P_rec · t_rec) / (t_peak + t_rec) (Tschakert and Hofmann, 2013).

In short HIIE, t_peak was 20 s, P_peak corresponded to P_max determined in IET, P_rec was set just below P_LTP1 (since P_LTP1 was suggested to be the point of the optimal lactate clearance rate), and t_rec (26.7 ± 13.4 s) was calculated via equation 1. Due to the fact that t_rec of short HIIE was calculated for each participant, the number of intervals was different across subjects, but the total exercise trial was approximately 28 min.

CE was performed for 28 min at a target workload equating to P_mean of both HIIE tests.

A 12-lead electrocardiogram (ZAN 800, ZAN, Winkling, Germany) was obtained from each subject during all tests supervised by an experienced physician. Pulmonary gas-exchange variables were collected continuously during all tests by breath-by-breath measurement and were averaged over 5 s periods (ZAN 600, ZAN, Winkling, Germany). VO_2max was defined as the highest 30 sec average value of oxygen uptake. HR data averaged over 5 s periods were also obtained during all tests via chest belt telemetry (PE 4000, Polar Electro, Kempele, Finland). Blood lactate and blood glucose concentrations obtained from capillary blood samples taken from ear lobes during all tests were measured via the fully enzymatic-amperometric method (Biosen S-line, EKF diagnostics, Barleben, Germany).

During IET, capillary blood samples were taken at the end of the rest and warm-up periods, at the end of each workload step, and at the end of active and passive recovery. During each of the three exercise sessions, capillary blood samples were taken accordingly at the end of the rest and 3 min warm up phase, after 1, 3, 5, and 7 min of the adaptation phase and after the 3 min active and 3 min passive recovery. During the specific exercise regimes, the times of blood collection differed: in CE after 1, 2, 3, 4, 5, 10, 15, 20, 25, and 28 min; in 4 x 4 HIIE after 2 and 4 min of the peak workload phases and after 1 and 3 min of the recovery phases; in short HIIE 4 blood collections within 7 min temporally in accordance with long HIIE.

The determination of individual turn points during IET (LTP₁, LTP₂) was accomplished by means of a computer-supported linear regression turn point model within defined regions of interest (ROI) (Hofmann and Tschakert, 2011). ROI for LTP₁ (and VT₁) was between La (and VE) at first workload and La (and VE) at 70 % of P_max, ROI for LTP₂ (and VT₂) was between La (and VE) at LTP₁ and La (and VE) at P_max (Hofmann et al., 1997, 2001).

For long and short HIIE and CE, mean values for particular parameters were calculated by averaging the values of each subject during the specific intermittent or continuous exercise. Peak values for particular parameters represent the average of the maximum single value of each participant during the specific intermittent or continuous exercise test.

All data are presented as mean ± SD and were analyzed using SPSS (IBM SPSS Statistics 19). A one-way repeated measures ANOVA (within factors) was conducted in order to determine the effects of different exercise regimes on the acute response of metabolic and cardiorespiratory parameters. When the analysis revealed a significant difference, post-hoc paired t-tests with a Bonferroni correction were used to locate the origin of the significant difference. Statistical significance was accepted if p < 0.05.

The lactate performance curve and the heart rate performance curve (HRPC) are presented in Figure 1. The blood lactate curve showed three phases of blood lactate appearance and two corresponding turn points (LTP₁, LTP₂). LTP₁ and LTP₂ were significantly related to the first (VT₁) and second ventilatory threshold (VT₂) with no significant difference in power output (data not shown).

All subjects completed all exercise sessions except for one participant who terminated the 4 x 4 min HIIE two min before the end of the session due to exhaustion. P_peak was significantly different (p < 0.05) between short HIIE (340.0 ± 47.3 W), long HIIE (279.2 ± 51.8 W), and CE (213.2 ± 42.0 W). P_mean was 213.2 ± 42.0 W in all three tests corresponding to 88.0 ± 8.5 % of P_LTP2. Mean and peak values for La, HR, VO₂, and the respiratory exchange ratio (RER) during the three different exercise regimes are presented in Table 1.

Lactate: Since P_mean was below P_LTP2 (88.0 ± 8.5 %), a lactate steady state was reached in CE as expected. Importantly, a lactate steady state was also reached in short HIIE but not in long HIIE (Fig. 2a). The comparison of all three exercise modes revealed significantly higher mean and peak La values in long HIIE compared to short HIIE and CE (p < 0.05) but no significant difference between short HIIE and CE (Figure 2a). Peak La during long HIIE was even higher than the maximal La value determined in IET.

Heart rate and oxygen uptake: HR values increased slightly during long and short HIIE and CE (Fig. 2b), but there was no significant difference for mean HR between the three tests. However, peak HR was significantly higher in long HIIE compared to short HIIE and CE (p < 0.05); but, there was no significant difference between short HIIE and CE (Figure 2b).

No significant difference could be found between mean and peak VO₂ values during long HIIE, short HIIE, and CE (Figure 2c).

Respiratory Exchange Ratio (RER): Our study revealed significantly higher mean and peak RER values in long HIIE than in short HIIE and CE (p < 0.05) with no significant difference between short HIIE and CE (Figure 2d). The mean and peak RER values decreased with time in all three exercise tests (mean: from 1.03 ± 0.04 to 0.96 ± 0.03; peak: from 1.11 ± 0.04 to 1.05 ± 0.04) (Figure 2d).

Regulation and predictability of the acute physiological response using P_mean: Given the acute metabolic and peak cardiorespiratory response to CE was not significantly different from short 20 s HIIE (LaSS in both exercise modes) but significantly lower than long HIIE, we demonstrated the acute physiological response to short HIIE but not to long HIIE was controllable and predictable from P_mean.

This study investigated the acute metabolic and cardiorespiratory response to long and short HIIE compared to CE as well as the predictability of this acute response using P_mean according to equation 1 for both HIIE models in young, healthy, and well-trained subjects.

Our study revealed that short HIIE (t_peak = 20 s; P_peak = P_max from IET) induced an acute metabolic and peak cardiorespiratory response that was not significantly different compared to CE but significantly lower than in long HIIE. Short HIIE was “aerobic” in contrast to long HIIE despite a significantly higher P_peak in the short intervals. In addition, we found the acute physiological response to short HIIE but not to long HIIE could be controlled for using P_mean.

Due to the fact that P_mean was lower than P_LTP2 from IET (88.0 ± 8.5 %), “aerobic” conditions and a lactate steady state, respectively, were targeted in all tests. We found that only CE and short HIIE showed a LaSS and therefore were “aerobic”. Long HIIE was not “aerobic” since it showed no LaSS and it induced blood lactate levels approximating maximal values. These data support the results of Wallner et al. (2013) who investigated the acute physiological response to short HIIE in trained runners.

As emphasized earlier by Astrand et al. (1960), Saltin et al. (1976), and recently by Tschakert and Hofmann (2013), the acute metabolic response to HIIE is strongly influenced by the combination of t_peak and P_peak; if P_peak is set above P_LTP2 (as it is usually done), blood lactate concentration increases with t_peak (Beneke et al., 2011; Smekal et al., 2012).

There is no doubt that combinations of t_peak and P_peak other than the combination used for our short HIIE regime may also generate a balance between lactate production and clearance. Nonetheless, one should be aware of the fact that the higher P_peak is, the shorter t_peak must be (Tschakert and Hofmann, 2013).

As illustrated in Figure 2a and 2d, the increase of net blood lactate (7.45 mmol·l^-1; 1.62 mmol·l^-1; 1.02 mmol·l^-1; 0.42 mmol·l^-1) as well as the mean and peak RER values during the four peak workload phases of 4 x 4 min HIIE decreased with each interval. Related to the findings of Parolin et al. (1999), our data suggest that the first 4 min high-intensity exercise bout induced a considerable metabolic acidosis that led to an inhibition of glycolysis and, consequently, to an increased contribution of aerobic metabolism for ATP re-synthesis during the peak workload phases of intervals 2-4. The increase of mean VO₂ from 3.30 ± 0.49 l·min^-1 during the first peak workload phase up to 3.57 ± 0.60 l·min^-1 during the last peak workload phase supports this assumption. These metabolic conditions may help explain the significant aerobic adaptations discovered in different 4 x 4 HIIE training studies (Helgerud et al., 2007; Rognmo et al., 2004; Wisloff et al., 2007).

The fact that mean values for HR and VO₂ were not significantly different between all tests (Table 1) was not surprising given mean load and exercise durations were equal. However, the significantly higher peak HR values induced by long HIIE compared to both other tests (Table 1) reflected temporarily elevated cardiorespiratory demands during the 4 x 4 min HIIE regime. In short HIIE, the oscillation of peak (and recovery) HR values around HR_mean remained low because of the short t_peak of 20 s. As a consequence, the peak HR values of short HIIE and CE were similar. This is remarkable given the high peak workload in short HIIE corresponding to P_max from IET. Our results are in accordance with the fundamental findings of Astrand et al. (1960) and Saltin et al. (1976) and support the results of Meyer et al. (1997) who have successfully applied HIIE in clinical populations. Meyer et al. (1998) have also shown remarkably stable values for left ventricular function during short HIIE similar to that used in this study, even in patients with heart disease, including heart failure.

Our approach to the exercise intensity prescription in long HIIE (power output at %HR_max) differed from that in the original Norwegian 4 x 4 HIIE model (%HR_max) (Helgerud et al., 2007). Therefore, we compared heart rate during peak workload phases in long HIIE (power output at 95 % HR_max from IET) and the 95 % HR_max value from IET. We found average peak HR at the end of each of the four peak workload phases (180.9 ± 5.6 b·min^-1 = 95.4 %HR_max) was not significantly different from 95 %HR_max from IET (180.2 ± 4.1 b·min^-1).

The peak power output at 95 %HR_max we used as P_peak for long HIIE in our study represented the upper limit of the range of 85 - 95 %HR_max for the original 4 x 4 HIIE model applied in both healthy (Helgerud et al., 2007) and diseased populations (Wisloff et al., 2007). However, exercise intensities of 90 %HR_max - or even intensities of 85 %HR_max, particularly in patients suffering from cardiovascular diseases treated with beta blockers (Hofmann et al., 2005; Wonisch et al., 2003) - might just as well correspond to workloads above the second turn point and induce an accordingly high acute physiological response (Hofmann et al., 2001).

Since all tests were matched for P_mean and total exercise duration, the acute physiological responses induced by CE were used as reference values for the regulation and predictability of the acute response to both interval tests. The acute metabolic and cardiorespiratory response to short 20 s HIIE but not to long 4 x 4 min HIIE was shown to be predictable and controllable using P_mean.

This indicates that, despite high peak workloads, the aerobic short HIIE regime allows a deliberately aimed triggering of specific and desired or required acute physiological responses (from very low up to markedly high mean and peak acute responses) dependent on the setting of P_mean and using equation 1. As a consequence, aerobic short HIIE can be applied as an endurance training strategy in order to pursue particular training goals in different training periods - both as basic endurance training with a low P_mean during the first preparation period and as competition-specific endurance training with a high P_mean close to a competition (Wallner et al., 2013). Moreover, given the marked difference in the acute physiological response between the two interval protocols, we suggest aerobic short HIIE is associated with lower health risks compared to long HIIE in patients suffering from a variety of chronic diseases. This suggestion is supported by Keteyian (2012) who pointed to the elevated health risks generated by the 4 x 4 min HIIE regime.

In contrast, long HIIE such as the 4 x 4 min model does not allow low acute metabolic and peak cardiorespiratory responses if P_peak is set above P_LTP2 even if P_mean is low. Therefore, use of a long HIIE regime is suggested only in particular training periods and healthy subjects.

An additional aspect noticed in our study was the fact that in long HIIE, the prescription of exercise intensity by means of % HR_max from IET resulted in considerably different values for P_peak, P_mean, and P_rec across subjects with respect to their individual P_LTP2 assessed in IET (minimum vs. maximum value for P_peak: 103.3 vs. 129.6 %P_LTP2; for P_mean: 75.1 vs. 101.6 %P_LTP2; for P_rec: 37.6 vs. 64.8 %P_LTP2). Since CE and both HIIE modes were matched for P_mean, the inter-individual diversity of P_mean was apparent in all tests. Hence, the relative acute cardiorespiratory and metabolic response during exercise was substantially different across subjects. This inter-individual disparity was caused by different patterns of the heart rate performance curve determined in IET and, as a consequence, by markedly differing %HR_max values at LTP₁ and LTP₂ (minimum vs. maximum value for LTP₁: 57.07 vs. 80.53 %HR_max; for LTP₂: 84.34 vs. 94.21 %HR_max). This was previously shown by Hofmann et al. (2001, 2005), Tabet et al. (2006), and Wonisch et al. (2003) and recently emphasized by Hofmann and Tschakert (2011) and Tschakert and Hofmann (2013).

In addition, if exercise intensity is prescribed via %HR_max, the time it takes for the participants to reach their individual target HR remains unspecified. No information is available about the power output and the metabolic situation until the target HR is reached. Therefore, we suggest that an accurate prescription of exercise intensities by means of %HR_max is inadequate particularly for intermittent exercise with short peak load durations up to 30 s.

Based on the previously established standards to prescribe exercise intensities for continuous exercise with respect to the lactate turn points (Hofmann and Tschakert, 2011; Smekal et al., 2012), we confirm our earlier recommendation (Tschakert and Hofmann, 2013) to use %P_LTP2 as P_mean, %P_LTP1 as P_rec, and %P_max as P_peak for the prescription of aerobic HIIE.

We must admit the number of participants (n = 6) was rather small in our study. However, the statistical power analysis revealed the statistical power was sufficient for our experimental design. Despite the small number of subjects, the difference in the acute metabolic and peak cardiorespiratory response between short and long HIIE was distinct and in accordance with the fundamental findings of Astrand et al. (1960).

A limit of this study was that P_mean was not deliberately set using % P_LTP2 as recommended by the authors (see above). We wanted to use the original Norwegian 4 x 4 HIIE prescription model (Helgerud et al., 2007), which dictated the setting of the intensity and duration of peak workload and recovery phases. Therefore, P_mean was calculated for the 4 x 4 min HIIE regime using equation 1 and adopted for the other two tests since the intent was to match the three exercise modes for P_mean. However, average P_mean across subjects corresponded to 88.0 ± 8.46 % of P_LTP2 from IET and, therefore, was in a desired range slightly below the power output at the maximal LaSS for CE.

Our study clearly revealed, in short HIIE, the acute metabolic and cardiorespiratory response is lower than in long HIIE and not different from CE, despite a considerably higher P_peak in short HIIE. With a P_mean below P_LTP2, a LaSS can be reached in CE and in short HIIE (“aerobic” exercise) but not using long HIIE. Moreover, the acute physiological response to short HIIE but not to long HIIE can be controllable and predictable using P_mean. Consequently, short HIIE can be expected to generate a longer total exercise duration than long HIIE. In addition, short HIIE is expected to allow directed triggering of specific acute physiological responses. Therefore, short HIIE is applicable to different training periods and subjects dependent on the setting of P_mean. In addition, data from our study suggest health risks might effectively be reduced in short HIIE compared to long HIIE for diseased populations.

Further research concerning the detailed acute physiological response and long-term effects induced by different HIIE prescriptions in different populations continues to be required (Hawley, 2008). In particular, studies are needed to investigate if “aerobic” short HIIE induces similar muscular and systemic training adaptations compared to long HIIE. Therefore, further methodological investigations including randomized controlled training intervention studies in both healthy and diseased individuals are required especially for short interval training programs.