Endurance training of older men: responses to submaximal exercise.

The purpose of this study was to quantify the exercise response of older subjects on a time-to-fatigue (TTF) submaximal performance test before and after a training program. Eight older men (67.4 +/- 4.8 yr) performed two maximal treadmill tests to determine maximum oxygen uptake (VO2max) and ventilation threshold (TVE) and a constant-load submaximal exercise treadmill test that required an oxygen uptake (VO2) between TVE and VO2max. The submaximal test, performed at the same absolute work rate before and after the training program, was performed to volitional fatigue to measure endurance time. The men trained under supervision at an individualized pace representing approximately 70% of VO2max (80% maximum heart rate) for 1 h, four times per week for 9 wk. Significant increases were demonstrated for VO2max (ml.kg-1.min-1; 10.6%); maximal ventilation (VE, l/min; 11.6%), and TVE (l/min; 9.8%). Weight decreased 2.1%. Performance time on the TTF test increased by 180% (7.3 +/- 3.0 to 20.4 +/- 13.5 min). The similar end points for VO2, VE, and heart rate during the TTF and maximal treadmill tests established that the TTF test was stopped because of physiological limitations. The increase in performance time among the subjects was significantly correlated with improvements in VO2max and TVE, with the submaximal work rate representing a VO2 above TVE by 88% of the difference between TVE and VO2max pretraining and 73% of this difference on posttraining values.     

Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs

Endurance training-induced changes in hemodynamic traits are heritable. However, few genes associated with heart rate training responses have been identified. The purpose of our study was to perform a genome-wide association study to uncover DNA sequence variants associated with submaximal exercise heart rate training responses in the HERITAGE Family Study. Heart rate was measured during steady-state exercise at 50 W (HR50) on 2 separate days before and after a 20-wk endurance training program in 483 white subjects from 99 families. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. After quality control procedures, 320,000 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study analyses, which were performed using the MERLIN software package (single-SNP analyses and conditional heritability tests) and standard regression models (multivariate analyses). The strongest associations for HR50 training response adjusted for age, sex, body mass index, and baseline HR50 were detected with SNPs at the YWHAQ locus on chromosome 2p25 (P = 8.1 × 10(-7)), the RBPMS locus on chromosome 8p12 (P = 3.8 × 10(-6)), and the CREB1 locus on chromosome 2q34 (P = 1.6 × 10(-5)). In addition, 37 other SNPs showed P values <9.9 × 10(-5). After removal of redundant SNPs, the 10 most significant SNPs explained 35.9% of the ΔHR50 variance in a multivariate regression model. Conditional heritability tests showed that nine of these SNPs (all intragenic) accounted for 100% of the ΔHR50 heritability. Our results indicate that SNPs in nine genes related to cardiomyocyte and neuronal functions, as well as cardiac memory formation, fully account for the heritability of the submaximal heart rate training response.     

Variation in heart rate during submaximal exercise: implications for monitoring training

A change in heart rate at a controlled submaximal exercise intensity is used as a marker of training status. However, the standard error of measurement has not been studied systematically, and therefore a change in heart rate, which can be considered relevant, has not been determined. Forty-four subjects (26.5 +/- 5.4 years; mean +/- standard deviation) participated in a submaximal running test at the same time of day for 5 consecutive days. Heart rates were determined during each of the 4 exercise intensities (2 minutes each) of increasing intensity and during the 1-minute recovery period after each stage. The repeatability of the heart rate on a day-to-day basis during the stages and recovery periods were high (intraclass correlation coefficient: 95% confidence interval R = 0.94- 0.99). The lowest variation in heart rate occurred in the fourth stage ( approximately 90% maximum heart rate) with heart rate varying 5 +/- 2 b.min(-1) (95% confidence interval for coefficient of variation = 1.1-1.4%). In conclusion, the standard error of measurement of submaximal heart rate is 1.1-1.4%. This magnitude of measurement error needs to be considered when heart rate is used as a marker of training status.     

Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation.

Both a large heart rate (HR) increase at exercise onset and a slow heart rate (HR) recovery following the termination of exercise have been linked to an increased risk for ventricular fibrillation (VF) in patients with coronary artery disease. Endurance exercise training can alter cardiac autonomic regulation. Therefore, it is possible that this intervention could restore a more normal HR regulation in high-risk individuals. To test this hypothesis, HR and HR variability (HRV, 0.24- to 1.04-Hz frequency component; an index of cardiac vagal activity) responses to submaximal exercise were measured 30, 60, and 120 s after exercise onset and 30, 60, and 120 s following the termination of exercise in dogs with healed myocardial infarctions known to be susceptible (n = 19) to VF (induced by a 2-min coronary occlusion during the last minute of a submaximal exercise test). These studies were then repeated after either a 10-wk exercise program (treadmill running, n = 10) or an equivalent sedentary period (n = 9). After 10 wk, the response to exercise was not altered in the sedentary animals. In contrast, endurance exercise increased indexes of cardiac vagal activity such that HR at exercise onset was reduced (30 s after exercise onset: HR pretraining 179 +/- 8.4 vs. posttraining 151.4 +/- 6.6 beats/min; HRV pretraining 4.0 +/- 0.4 vs. posttraining 5.8 +/- 0.4 ln ms(2)), whereas HR recovery 30 s after the termination of exercise increased (HR pretraining 186 +/- 7.8 vs. posttraining 159.4 +/- 7.7 beats/min; HRV pretraining 2.4 +/- 0.3 vs. posttraining 4.0 +/- 0.6 ln ms(2)). Thus endurance exercise training restored a more normal HR regulation in dogs susceptible to VF.     

Endurance training in older men and women II. Blood lactate response to submaximal exercise

Seven men and four women (age 63 +/- 2 yr, mean +/- SD, range 61-67 yr) participated in a 12-mo endurance training program to determine the effects of low-intensity (LI) and high-intensity (HI) training on the blood lactate response to submaximal exercise in older individuals. Maximal oxygen uptake (VO2max), blood lactate, O2 uptake (VO2), heart rate (HR), ventilation (VE), and respiratory exchange ratio (R) during three submaximal exercise bouts (65-90% VO2max) were determined before training, after 6 mo of LI training, and after an additional 6 mo of HI training. VO2max (ml X kg-1 X min-1) was increased 12% after LI training (P less than 0.05), while HI training induced a further increase of 18% (P less than 0.01). Lactate, HR, VE, and R were significantly lower (P less than 0.05) at the same absolute work rates after LI training, while HI training induced further but smaller reductions in these parameters (P greater than 0.05). In general, at the same relative work rates (ie., % of VO2max) after training, lactate was lower or unchanged, HR and R were unchanged, and VO2 and VE were higher. These findings indicate that LI training in older individuals results in adaptations in the response to submaximal exercise that are similar to those observed in younger populations and that additional higher intensity training results in further but less-marked changes.     

Plasma norepinephrine and heart rate dynamics during recovery from submaximal exercise in man

The time course of heart rate (HR) and venous blood norepinephrine concentration [NE], as an expression of the sympathetic nervous activity (SNA), was studied in six sedentary young men during recovery from three periods of cycle ergometer exercise at 21% +/- 2.8%, 43% +/- 2.1% and 65% +/- 2.3% of VO2max respectively (mean +/- SE). The HR decreased mono-exponentially with tau values of 13.6 +/- 1.6 s, 32.7 +/- 5.6 s and 55.8 +/- 8.1 s respectively in the three periods of exercise. At the low exercise level no change in [NE] was found. At medium and high exercise intensity: (a) [NE] increased significantly at the 5th min of exercise (delta [NE] = 207.7 +/- 22.5 pg.ml-1 and 521.3 +/- 58.3 pg.ml-1 respectively); (b) after a time lag of 1 min [NE] decreased exponentially (tau = 87 s and 101 s respectively); (c) in the 1st min HR decreased about 35 beats.min-1; (d) from the 2nd to 5th min of recovery HR and [NE] were linearly related (100 pg.ml-1 delta [NE] congruent to 5 beats.min-1). In the 1st min of recovery, independent of the exercise intensity, the adjustment of HR appears to have been due mainly to the prompt restoration of vagal tone. The further decrease in HR toward the resting value could then be attributed to the return of SNA to the pre-exercise level.     

Relation of heart rate to percent VO2 peak during submaximal exercise in the heat.

We tested the hypothesis that elevation in heart rate (HR) during submaximal exercise in the heat is related, in part, to increased percentage of maximal O(2) uptake (%Vo(2 max)) utilized due to reduced maximal O(2) uptake (Vo(2 max)) measured after exercise under the same thermal conditions. Peak O(2) uptake (Vo(2 peak)), O(2) uptake, and HR during submaximal exercise were measured in 22 male and female runners under four environmental conditions designed to manipulate HR during submaximal exercise and Vo(2 peak). The conditions involved walking for 20 min at approximately 33% of control Vo(2 max) in 25, 35, 40, and 45 degrees C followed immediately by measurement of Vo(2 peak) in the same thermal environment. Vo(2 peak) decreased progressively (3.77 +/- 0.19, 3.61 +/- 0.18, 3.44 +/- 0.17, and 3.13 +/- 0.16 l/min) and HR at the end of the submaximal exercise increased progressively (107 +/- 2, 112 +/- 2, 120 +/- 2, and 137 +/- 2 beats/min) with increasing ambient temperature (T(a)). HR and %Vo(2 peak) increased in an identical fashion with increasing T(a). We conclude that elevation in HR during submaximal exercise in the heat is related, in part, to the increase in %Vo(2 peak) utilized, which is caused by reduced Vo(2 peak) measured during exercise in the heat. At high T(a), the dissociation of HR from %Vo(2 peak) measured after sustained submaximal exercise is less than if Vo(2 max) is assumed to be unchanged during exercise in the heat.     

Genome-wide linkage scan for submaximal exercise heart rate in the HERITAGE family study

The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training program in blacks and whites of the HERITAGE Family Study. A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady-state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 W (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (posttraining minus baseline, Delta) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used, a multipoint variance components and a regression-based multipoint linkage analysis. In whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD = 2.64; P = 0.0002) and DeltaHR60 (LOD = 2.10; P = 0.0009) and on chromosome 2q33.3 for DeltaHR50 (LOD = 2.13; P = 0.0009). In blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD = 2.43, P = 0.0004 with D10S597). The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites.     

Transient ventilatory and heart rate responses to moderate nonabrupt pseudorandom exercise

Dynamic responses of inspired minute ventilation, CO2 and O2 end-tidal gas fractions, and heart rate were obtained from six normal human volunteers in response to a complex dynamic exercise challenge. Subjects pedalled a chair ergometer at constant frequency. The retarding torque applied to the ergometer pedals was controlled by a low-pass-filtered pseudorandom binary sequence (fPRBS), which provided a complex, nonanticipatory exercise stimulus containing sufficient high- and low-frequency energy to excite the small signal, broadband ventilatory response. The exercise range was chosen to produce a mean level of O2 consumption at or below 50% maximum O2 consumption. Cross-covariant analysis of the fPRBS exercise with breath-by-breath ventilation provided an estimate of the dynamic (impulse) response to exercise, which contained both fast phase 1 and slow phase 2 components. The initial, phase one, hyperpnea occurred within the same breath as the exercise transition and preceded a hypocapnic response. The phase one hyperpnea represented 26% of the total ventilatory response. The secondary, phase 2, hyperpnea was delayed several breaths from the onset of phase 1. It contained slower dynamics and followed a hypercapnic response. Heart rate increased abruptly during phase 1, peaked near the phase 1-to-2 boundary, and then decreased rapidly. The experimental protocol was designed to minimize the subjective response and provide an adequate stimulus for the faster time constants. Results obtained from these experiments were consistent with a nonhumoral induced phase 1 exercise hyperpnea.     

Cardiac vagal modulation of heart rate during prolonged submaximal exercise in animals with healed myocardial infarctions: effects of training

The present study investigated the effects of long-duration exercise on heart rate variability [as a marker of cardiac vagal tone (VT)]. Heart rate variability (time series analysis) was measured in mongrel dogs (n = 24) with healed myocardial infarctions during 1 h of submaximal exercise (treadmill running at 6.4 km/h at 10% grade). Long-duration exercise provoked a significant (ANOVA, all P < 0.01, means +/- SD) increase in heart rate (1st min, 165.3 +/- 15.6 vs. last min, 197.5 +/- 21.5 beats/min) and significant reductions in high frequency (0.24 to 1.04 Hz) power (VT: 1st min, 3.7 +/- 1.5 vs. last min, 1.0 +/- 0.9 ln ms(2)), R-R interval range (1st min, 107.9 +/- 38.3 vs. last min, 28.8 +/- 13.2 ms), and R-R interval SD (1st min, 24.3 +/- 7.7 vs. last min 6.3 +/- 1.7 ms). Because endurance exercise training can increase cardiac vagal regulation, the studies were repeated after either a 10-wk exercise training (n = 9) or a 10-wk sedentary period (n = 7). After training was completed, long-duration exercise elicited smaller increases in heart rate (pretraining: 1st min, 156.0 +/- 13.8 vs. last min, 189.6 +/- 21.9 beats/min; and posttraining: 1st min, 149.8 +/- 14.6 vs. last min, 172.7 +/- 8.8 beats/min) and smaller reductions in heart rate variability (e.g., VT, pretraining: 1st min, 4.2 +/- 1.7 vs. last min, 0.9 +/- 1.1 ln ms(2); and posttraining: 1st min, 4.8 +/- 1.1 vs. last min, 2.0 +/- 0.6 ln ms(2)). The response to long-duration exercise did not change in the sedentary animals. Thus the heart rate increase that accompanies long-duration exercise results, at least in part, from reductions in cardiac vagal regulation. Furthermore, exercise training attenuated these exercise-induced reductions in heart rate variability, suggesting maintenance of a higher cardiac vagal activity during exercise in the trained state.     

Effect of dietary omega-3 fatty acids on the heart rate and the heart rate variability responses to myocardial ischemia or submaximal exercise

The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been reported to decrease resting heart rate (HR) and increase heart rate variability (HRV). However, the effects of n-3 PUFAs on these variables in response to a physiological stress (e.g., exercise or acute myocardial ischemia), particularly in postmyocardial infarction (MI) patients, are unknown. Therefore, HR and HRV (high frequency and total R-R interval variability) were evaluated at rest, during submaximal exercise, and during a 2-min coronary artery occlusion at rest and before and 3 mo after n-3 PUFA treatment in dogs with healed MI (n = 59). The dogs were randomly assigned to either placebo (1 g/day corn oil, n = 19) or n-3 PUFA supplement (docosahexaenoic acid + eicosapentaenoic acid ethyl esters; 1 g/day, n = 6; 2 g/day, n = 12; or 4 g/day, n = 22) groups. The treatment elicited significant (P < 0.01) dose-dependent increases in right atrial n-3 PUFA levels but dose-independent reductions in resting HR and increases in resting HRV. In contrast, n-3 PUFAs did not attenuate the large changes in HR or HRV induced by either the coronary occlusion or submaximal exercise. These data demonstrate that dietary n-3 PUFA decreased resting (i.e., preexercise or preocclusion) HR and increased resting HRV but did not alter the cardiac response to physiologic challenges.     

Influence of training on sleeping heart rate following daytime exercise

The purpose of this investigation was to examine the influence of daytime exercise on heart rate during sleep. Nine, untrained male college students volunteered to participate. They cycled at 75% maximum oxygen uptake, ( O_2max) 30 min·day^–1 for 12 weeks. The exercise duration was increased by 5 min every 4 weeks from 30 to 40 min per session. Post-training O_2max[mean (SE): 48.9 (1.7) ml · kg^–1 · min^–1] values were significantly (P<0.01) higher than pre-training [45.5 (1.8) ml-kg^–1·min^–1] values. Before and after training, sleeping heart rate was assessed on two separate nights. Data were obtained during a night following 30 min of daytime cycling at 75 (6) % O_2maxand on a night in which no daytime exercise was performed. A three-way repeated measures ANOVA [training status (pre-/post-training) × activity (exercise day/nonexercise day) × sleep time (18 epochs of 20 min each)] revealed a significant main effect for sleep time (P < 0.001) as well as a sleep time × training status interaction (P<0.02). No significant difference in sleeping heart rate was noted when exercise and non-exercise days were compared both before and after training. It is concluded that endurance training in these young adult men: (1) hastens the achievement of baseline heart rate during sleep, and (2) does not moderate the relationship between an acute bout of daytime exercise and sleeping heart rate.     

Inhibition of nitric oxide synthase slows heart rate recovery from cholinergic activation

The role ofnitric oxide (NO) in the cholinergic regulation of heart rate(HR) recovery from an aspect of simulated exercise wasinvestigated in atria isolated from guinea pig to test the hypothesisthat NO may be involved in the cholinergic antagonism of the positivechronotropic response to adrenergic stimulation. Inhibition of NOsynthesis withN^G-monomethyl-L-arginine(L-NMMA, 100 µM) significantlyslowed the time course of the reduction in HR without affecting themagnitude of the response elicited by bath-applied ACh (100 nM) orvagal nerve stimulation (2 Hz). The half-times(t_1/2) of responses were 3.99 ± 0.41 s in control vs. 7.49 ± 0.68 s inL-NMMA(P < 0.05). This was dependent onprior adrenergic stimulation (norepinephrine, 1 µM). The effect ofL-NMMA was reversed byL-arginine (1 mM; t_1/2 4.62 ± 0.39 s). The calcium-channelantagonist nifedipine (0.2 µM) also slowed the kinetics of thereduction in HR caused by vagal nerve stimulation. However, thet_1/2 for the reduction in HR with antagonists (2 mM Cs⁺ and 1 µM ZD-7288) of thehyperpolarization-activated current were significantlyfaster compared with control. There was no additional effect ofL-NMMA orL-NMMA+L-arginineon vagal stimulation in groups treated with nifedipine,Cs⁺, or ZD-7288. Weconclude that NO contributes to the cholinergic antagonism of thepositive cardiac chronotropic effects of adrenergic stimulation byaccelerating the HR response to vagal stimulation. This may involve aninterplay between two pacemaking currents (L-type calcium channelcurrent and hyperpolarization-activated current). Whether NO modulatesthe vagal control of HR recovery from actual exercise remains to bedetermined.