Improved pulmonary function is associated with reduced inflammation after hybrid whole-body exercise training in persons with spinal cord injury.

NEW FINDINGS: What is the central question of this study? Does 12 weeks of functional electrical stimulation (FES) rowing exercise training lead to suppressed systemic inflammation and an improvement in pulmonary function in persons with sub-acute spinal cord injury (SCI)? What is the main finding and its importance? Twelve weeks of FES rowing exercise improves pulmonary function and the magnitude of improvement is associated with reductions in inflammatory biomarkers. Thus, interventions targeting inflammation may lead to better pulmonary outcomes for person with sub-acute SCI. ABSTRACT: The current study was designed to test the hypotheses that (1) reducing systemic inflammation via a 12-week functional electrical stimulation rowing exercise training (FESRT) prescription results in augmented pulmonary function, and (2) the magnitude of improvement in pulmonary function is inversely associated with the magnitude of systemic inflammation suppression in persons with sub-acute (≤2 years) spinal cord injury (SCI). We conducted a retrospective analysis of a randomized controlled trial (NCT#02139436). Twenty-one participants were enrolled (standard of care (SOC; n = 9) or FESRT (n = 12)). The exercise prescription was three sessions/week at 70-85% of peak heart rate. A two-way analysis of covariance and regression analysis was used to assess group differences and associations between pulmonary function, log transformed high-sensitivity C-reactive protein (hsCRPlog ) and white blood cell count (WBC). Following FESRT, clinically significant improvements in forced expiratory volume in 1 s (FEV1 ; 0.25 (0.08-0.43) vs. -0.06 (-0.26 to 0.15) litres) and forced vital capacity (0.22 (0.04-0.39) vs. 0.08 (-0.29 to 0.12) litres) were noted and systemic WBC (-1.45 (-2.48 to -0.50) vs. 0.41 (-0.74 to 1.56) µl) levels were suppressed compared to SOC (mean change (95% confidence interval); P < 0.05). Additionally, both ΔhsCRPlog and ΔWBC were predictors of ΔFEV1 (r2  = 0.89 and 0.43, respectively; P < 0.05). Twelve weeks of FESRT improves pulmonary function and reduces WBC in persons with sub-acute SCI. The potency of FESRT to augment pulmonary function may depend on adequate suppression of systemic inflammation.

Hybrid Functional Electrical Stimulation Improves Anaerobic Threshold in First Three Years after Spinal Cord Injury.

The purpose of the present investigation was to assess the effects of whole-body exercise on the anaerobic threshold in individuals with spinal cord injury (SCI). Maximal oxygen uptake (VO2max) and oxygen uptake at anaerobic threshold (AT) were measured before and after six months of hybrid functional electrical stimulation row training in 47 participants with SCI aged 19-63, neurological levels of injury C4-L1, American Spinal Injury Association Impairment Scale grades A-D, and time since injury at enrollment from three months to 40 years. Changes in VO2max differed with time since injury, with greater increases earlier post-injury. The early chronic group (<3 years since injury; n = 31) increased VO2max from 1.65 ± 0.54 L/min at baseline to 1.83 ± 0.66 L/min at six months (p < 0.05), while the late chronic group (>3 years since injury; n = 16) did not change (1.42 ± 0.44 at baseline to 1.47 ± 0.41 L/min at six months, p = 0.36). Consistent with VO2max changes, AT increased in the early chronic group (1.03 ± 0.31 to 1.20 ± 0.40 L/min, p < 0.05) and did not change in the late chronic group (0.99 ± 0.31 to 0.99 ± 0.26 L/min, p = 0.92). Cumulative duration of exercise training was positively correlated to change in VO2max (r = 0.475, p < 0.05) but not to change in AT. Hybrid functional electrical stimulation row training is effective for increasing aerobic capacity and anaerobic threshold in individuals with SCI; however, these fitness benefits are only significant in individuals initiating the exercise intervention within three years of injury.

Effect of hybrid FES exercise on body composition during the sub-acute phase of spinal cord injury.

OBJECTIVES: To determine the Effect of Hybrid functional electrically stimulated (FES) Exercise on Body Composition during the Sub-acute Phase of Spinal Cord Injury (SCI). DESIGN: Randomized Clinical Trial. SETTING: Rehabilitation Hospital. PARTICIPANTS: Patients within sub-acute phase (3-24 months) of SCI. INTERVENTIONS: We investigated if high-intensity exercise training via the addition of functional electrically stimulated (FES) leg muscles, provides sufficient stimulus to mitigate against body composition changes in the sub-acute phase after SCI. MAIN OUTCOME MEASURES: We explored potential effects of FES row training (FESRT) on body fat gain, lean mass loss, and cardiometabolic parameters and compared the effects of 6-month of FESRT (n = 18) to standard of care (SOC, n = 13). Those in SOC were crossed over to FESRT. RESULTS: FESRT resulted in greater exercise capacity and a tendency for lesser total body fat accumulation with a significant increase in total and leg lean mass (p<0.05). In addition pelvis and total bone mineral density declines were significantly less (p<0.05). Compared to SOC, FESRT did not lead to any significant difference in insulin sensitivity or serum lipids. However, HbA1C levels were significantly decreased in SOC participants who crossed over to 6-month FESRT. CONCLUSION: FESRT early after SCI provides a sufficient stimulus to mitigate against detrimental body composition changes. This may lead to prevention of losses in lean mass, including bone.

Gains in aerobic capacity with whole-body functional electrical stimulation row training and generalization to arms-only exercise after spinal cord injury.

STUDY DESIGN: Longitudinal study in adults (n = 27; 19-40 years old) with tetraplegic or paraplegic spinal cord injury (SCI). OBJECTIVES: Determine physiological adaptations and generalizable fitness effects of 6 months of whole-body exercise training using volitional arm and functional electrical stimulation (FES) leg rowing. SETTING: Outpatient hospital-based exercise facility and laboratory. METHODS: Participants enrolled in hybrid FES-row training (FESRT) and performed peak exercise tests with arms-only (AO; baseline and 6 months) and FES rowing (baseline, 3, 6 months). RESULTS: Participants demonstrated increased aerobic capacity (VO2peak) after FESRT (p < 0.001, np2 = 0.56) that tended to be higher when assessed with FES than AO rowing tests (0.15 ± 0.20 vs. 0.04 ± 0.22 L/min; p = 0.10). Changes in FES and AO VO2peak were significantly correlated (r = 0.55; p < 0.01), and 11 individuals demonstrated improvements (>6%) on both test formats. Younger age was the only difference between those who showed generalization of training effects and those who did not (mean age 26.6 ± 5.6 vs. 32.0 ± 5.7 years; p < 0.05) but changes in FES VO2peak correlated to time since injury in individuals <2 years post-SCI (r = -0.51, p < 0.01, n = 24). Lastly, VO2peak improvements were greater during the first 3 months vs. months 4-6 (+7.0% vs. +3.9%; p < 0.01) which suggests early training adaptations during FESRT. CONCLUSIONS: Gains in aerobic capacity after whole-body FESRT are better reflected during FES-row testing format. They relate to high-intensity exercise and appear early during training, but they may not generalize to equivalent increases in AO exercise in all individuals with SCI.

Cardiometabolic Effects of High-Intensity Hybrid Functional Electrical Stimulation Exercise after Spinal Cord Injury.

INTRODUCTION: The prevalence of cardiometabolic disease following spinal cord injury is known to be high. However, it is unknown whether engaging in high-intensity exercise, which is advocated by recent guidelines, is beneficial or feasible for these individuals. OBJECTIVE: To assess the effects of high-intensity, whole-body exercise on the prevalence of cardiometabolic disease in individuals with spinal cord injury. DESIGN: Combination of a randomized controlled trial and an open label intervention study of functional electrical stimulation legs plus arms rowing. SETTING: Outpatient academic rehabilitation hospital. PARTICIPANTS: Forty individuals with spinal cord injury, with American Spinal Injury Association (ASIA) impairments scales A-D and neurological levels of injury C1-T12. INTERVENTION: Six months of high-intensity, hybrid-functional electrical stimulation rowing. MAIN OUTCOME MEASURES: Change in VO2max , serum lipids, and insulin resistance, prevalence of cardiometabolic disease. RESULTS: Individuals averaged 42.1 ± 22.0 minutes of hybrid-functional electrical stimulation rowing a week over an average of 1.69 sessions per week over the 6 months of intervention. This amounted to an average of 170.9 ± 100 km rowed, at a mean heart rate of 82.7% of individualized maximum. Only one of 40 individuals met current exercise guidelines for the full 6 months. VO2max increased significantly (P < .001), yet prevalence of cardiometabolic disease did not change significantly (decrease from 22.5% to 20%, P = .70). Hemoglobin A1c did decrease significantly over this time (P = .01), although serum lipids and fasting glucose/insulin levels were unchanged. In exploratory subanalyses assessing individuals injured ≤12 months, those with more chronic injuries decreased their triglyceride-to-high-density lipoprotein (HDL) ratio (P = .04), a marker of cardiac mortality. Stratifying by neurological level of injury, individuals with paraplegia had worsened low-density lipoprotein (LDL) level (P = .02) and total cholesterol-to-HDL ratio (P = .04) over the 6-month intervention. CONCLUSIONS: Sustained high-intensity exercise with hybrid functional electrical stimulation rowing does not decrease the prevalence of cardiometabolic disease after spinal cord injury.

Serotonin 1A agonist and cardiopulmonary improvements with whole-body exercise in acute, high-level spinal cord injury: a retrospective analysis.

PURPOSE: High-level spinal cord injury (SCI) can result in spinal and supraspinal respiratory control deficits leading to insufficient ventilatory responses to exercise and training-related adaptations. We hypothesized a serotonin agonist, known to improve respiratory function in animal models, would improve adaptations to whole-body functional electrical stimulation (FES) exercise training in patients with acute high-level SCI. METHODS: We identified 10 patients (< 2 years of injury with SCI from C4 to T3) in our program who had performed 6 months of FES-row training while on Buspirone (29 ± 17 mg/day) between 2012 and 2018. We also identified well-matched individuals who trained for six months but not on Buspirone (n = 11). A peak incremental FES-rowing exercise test and resting pulmonary function test had been performed before and after training. RESULTS: Those on Buspirone demonstrated greater increases in peak oxygen consumption (VO2peak: + 0.24 ± 0.23 vs. + 0.10 ± 0.13 L/min, p = 0.08) and peak ventilation (VEpeak: + 6.5 ± 8.1 vs. - 0.7 ± 6.9 L/min, p < 0.05) compared to control. In addition, changes in VO2peak and VEpeak were correlated across all patients (r = 0.63, p < 0.01), but most strongly in those on Buspirone (r = 0.85, p < 0.01). Furthermore, changes in respiratory function correlated with increased peak tidal volume in the Buspirone group (r > 0.66, p < 0.05). CONCLUSION: These results suggest Buspirone improves cardiorespiratory adaptations to FES-exercise training in individuals with acute, high-level SCI. The strong association between increases in ventilatory and aerobic capacities suggests improved respiratory function is a mechanism; however, controlled studies are needed to determine if this preliminary finding is reproducible.

Ventilatory support during whole-body row training improves oxygen uptake efficiency in patients with high-level spinal cord injury: A pilot study.

High-level spinal cord injury (SCI) is characterized by profound respiratory compromise. One consequence is a limitation of whole-body exercise-based rehabilitation, reducing its cardioprotective effect. We investigated the use of ventilatory support during training on cardiorespiratory response to exercise. Nine subjects with high-level SCI (T3-C4) were included in this double-blind sham-controlled study. All had training adaptations plateauing for more than 6 months before enrolling in the study. After performing baseline assessment, participants were randomly assigned to continue training with non-invasive ventilation (NIV: n = 6: IPAP = 20 ± 2, EPAP: 3 cmH2O) or sham (n = 3: IPAP = 5, EPAP: 3 cmH2O) for 3 months and performed again maximal exercise tests. We compared the oxygen uptake efficiency slope (OUES, the rate of increases in VO2 in relation to increasing VE) before and after training. Training with NIV increased OUES both compared to baseline (4.1 ± 1.1 vs. 3.4 ± 1.0, i.e. +20 ± 12%, p < 0.05) and Sham (p = 0.01), representing an increase in ability to uptake oxygen for a given ventilation. This result was sustained without NIV during the test, suggesting improved cardiopulmonary reserve. Best responders were the youngest whose characteristics were very similar to sham participants. In addition, NIV tended to increase weekly rowing distance by 24% (p = 0.09, versus 10% in sham). Our results are very suggestive of a positive effect of ventilatory support during whole-body exercise in high-level SCI. Training adaptations found are of great importance since this sub-population of patients have the greatest need for exercise-based cardio-protection.

Acute Ventilatory Support During Whole-Body Hybrid Rowing in Patients With High-Level Spinal Cord Injury: A Randomized Controlled Crossover Trial.

BACKGROUND: High-level spinal cord injury (SCI) results in profound spinal and supraspinal deficits, leading to substantial ventilatory limitations during whole-body hybrid functional electrical stimulation (FES)-rowing, a form of exercise that markedly increases the active muscle mass via electrically induced leg contractions. This study tested the effect of noninvasive ventilation (NIV) on ventilatory and aerobic capacities in SCI. METHODS: This blinded, randomized crossover study enrolled 19 patients with SCI (level of injury ranging from C4 to T8). All patients were familiar with FES-rowing and had plateaued in their training-related increases in aerobic capacity. Patients performed two FES-rowing peak exercise tests with NIV or without NIV (sham). RESULTS: NIV increased exercise tidal volume (peak, 1.50 ± 0.31 L vs 1.36 ± 0.34 L; P < .05) and reduced breathing frequency (peak, 35 ± 7 beats/min vs 38 ± 6 beats/min; P < .05) compared with the sham test, leading to no change in alveolar ventilation but a trend toward increased oxygen uptake efficiency (P = .06). In those who reached peak oxygen consumption (Vo2peak) criteria (n = 13), NIV failed to significantly increase Vo2peak (1.73 ± 0.66 L/min vs 1.78 ± 0.59 L/min); however, the range of responses revealed a correlation between changes in peak alveolar ventilation and Vo2peak (r = 0.89; P < .05). Furthermore, those with higher level injuries and shorter time since injury exhibited the greatest increases in Vo2peak. CONCLUSIONS: Acute NIV can successfully improve ventilatory efficiency during FES exercise in SCI but may not improve Vo2peak in all patients. Those who benefit most seem to be patients with cervical SCI within a shorter time since injury. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT02865343 and NCT03267212; URL: www.clinicaltrials.gov.

Muscle Fatigue in Response to Electrical Stimulation Pattern and Frequency in Spinal Cord Injury.

BACKGROUND: Functional electrical stimulation (FES) is widely used to induce functional movements for paralyzed muscles. However, rapid muscle fatigue during FES-induced muscle contractions limits FES clinical efficacy. OBJECTIVE: To investigate muscle fatigue response across stimulation patterns and frequencies during FES in able-bodied individuals and in those with spinal cord injury (SCI). DESIGN: Four stimulation protocols combining 20 and 40 Hz average frequency with either constant frequency trains (CFTs) or with doublet frequency trains (DFTs) were applied to the quadriceps of seven adults with SCI and eight able-bodied participants. SETTING: A FES-row training laboratory. PARTICIPANTS: Seven individuals with SCI (one female; age range, 25 ± 6 years) and eight age-matched able-bodied participants (one female). INTERVENTION: None. MAIN OUTCOME MEASURES: Fatigue was defined as the number of contractions until force decreased by 20% from the target level of 25% maximal contraction force. The number of contractions and the stimulation current used during the four stimulation protocols were compared. RESULTS: There was a significant effect of frequency, as well as interaction between group and stimulation pattern (P < .05). In both groups, 20-Hz trains increased the number of contractions to fatigue compared to 40-Hz trains. However, the responses to the pattern of stimulation differed. In the able-bodied participants, CFT increased the number of contractions to fatigue compared to DFT, whereas in those with SCI, DFT increased the number of contractions to fatigue. In fact, DFT resulted in similar number of contractions to fatigue in both populations. CONCLUSIONS: These results indicate that DFT at 20 Hz may be a better stimulation protocol to delay fatigue onset in the SCI population than the other three protocols. In addition, this work implies that results from able-bodied persons may not be directly applicable to those with SCI.

Relationship of Spinal Cord Injury Level and Duration to Peak Aerobic Capacity With Arms-Only and Hybrid Functional Electrical Stimulation Rowing.

OBJECTIVE: The aim of the study was to assess the relationship of spinal cord injury level and duration to peak aerobic capacities during arms-only rowing compared with hybrid Functional Electrical Stimulation (FES)-rowing. DESIGN: Comparison of peak aerobic capacity (VO2), peak ventilation, peak respiratory exchange ratio, and peak heart rate were measured during arms-only rowing and FES-rowing obtained from graded exercise tests. RESULTS: Peak aerobic values were strongly related to injury level and injury duration for both arms-only rowing (r = 0.67, P < 0.05) and FES-rowing (r = 0.61, P < 0.05). Peak aerobic capacities were greater across all injury levels and durations with FES-rowing compared with arms-only rowing. Differences in VO2 were inversely related to injury level (r = 0.55, P < 0.05) with greater increases in VO2 in higher level injuries. Injury durations of less than 2 yrs had greater percent increases in VO2 with FES-rowing. CONCLUSIONS: FES-rowing acutely post injury may have the greatest effect to maintain function and improve VO2. This impact seems to be greatest in those with higher level injuries.

Assessing kinematics and kinetics of functional electrical stimulation rowing.

Hybrid functional electrical stimulation (FES) rowing has positive effects on cardiovascular fitness, producing significantly greater aerobic power than either upper body or FES exercise alone. However, there is minimal information on the kinematics, kinetics, and mechanical efficiency of FES-rowing in the spinal cord injured (SCI) population. This study examined the biomechanics of FES-rowing to determine how motions, forces, and aerobic demand change with increasing intensity. Six individuals with SCI and six able-bodied subjects performed a progressive aerobic capacity rowing test. Differences in kinematics (motion profiles), kinetics (forces produced by the feet and arms), external mechanical work, and mechanical efficiency (work produced/volume of oxygen consumed) were compared in able-bodied rowing vs. SCI FES-rowing at three comparable subpeak workloads. With increasing exercise intensity (measured as wattage), able-bodied rowing increased stroke rate by decreasing recovery time, while FES-rowing maintained a constant stroke rate, with no change in drive or recovery times. While able-bodied rowers increased leg and arm forces with increasing intensity, FES-rowers used only their arms to achieve a higher intensity with a constant and relatively low contribution of the legs. Oxygen consumption increased in both groups, but more so in able-bodied rowers, resulting in able-bodied rowers having twice the mechanical efficiency of FES-rowers. Our results suggest that despite its ability to allow for whole body exercise, the total force output achievable with FES-rowing results in only modest loading of the legs that affects overall rowing performance and that may limit forces applied to bone.

Ventilation Limits Aerobic Capacity after Functional Electrical Stimulation Row Training in High Spinal Cord Injury.

PURPOSE: In the able-bodied, exercise training results in increased ventilatory capacity to meet increased aerobic demands of trained skeletal muscle. However, after spinal cord injury (SCI), peak ventilation can be limited by pulmonary muscle denervation. In fact, peak ventilation may restrict aerobic capacity in direct relation to injury level. Hybrid functional electrical stimulation (FES) exercise training results in increased aerobic capacity and dissociation between aerobic capacity and injury level in those with injuries at T3 and below. However, injuries above T3 have the greatest pulmonary denervation, and ventilatory capacity may restrict the increase in aerobic capacity with hybrid FES training. METHODS: We assessed relationships among injury level, peak ventilation, and peak aerobic capacity and calculated oxygen uptake efficiency slope during hybrid FES exercise in 12 individuals (1 female) with SCI at level T2 to C4 (injury duration = 0.33-33 yr, age = 20-60 yr), before and after 6 months of FES-row training (FES-RT). RESULTS: Training increased peak aerobic capacity by 12% (P = 0.02) with only a modest increase in peak ventilation (7 of 12 subjects, P = 0.09). Both before and after training, injury level was directly related to peak ventilation (R = 0.48 and 0.43) and peak aerobic capacity (R = 0.70 and 0.55). Before training, the relationship of peak aerobic capacity to peak ventilation was strong (R = 0.62), however, after training, this relationship became almost completely linearized (R = 0.84). In addition, oxygen uptake efficiency slope increased by 11% (P < 0.05) after FES-RT. CONCLUSION: Despite the ability to increase exercise capacity via hybrid FES exercise, the inability to increase peak ventilation beyond limits set by SCI level in those with high-level injuries (above T3) appears to restrict aerobic capacity.

Hybrid functional electrical stimulation exercise training alters the relationship between spinal cord injury level and aerobic capacity.

OBJECTIVE: To test the hypothesis that hybrid functional electrical stimulation (FES) row training would improve aerobic capacity but that it would remain strongly linked to level of spinal cord lesion because of limited maximal ventilation. DESIGN: Longitudinal before-after trial of 6 months of FES row training. SETTING: Exercise for persons with disabilities program in a hospitaL. PARTICIPANTS: Volunteers (N=14; age range, 21-63y) with complete spinal cord injury (SCI) (T3-11) who are >2 years postinjury. INTERVENTION: Six months of FES row training preceded by a variable period of FES strength training. MAIN OUTCOME MEASURES: Peak aerobic capacity and peak exercise ventilation before and after 6 months of FES row training. RESULTS: FES row training significantly increased peak aerobic capacity and peak minute ventilation (both P<.05). Prior to FES row training, there was a close relation between level of SCI and peak aerobic capacity (adjusted R(2)=.40, P=.009) that was markedly reduced after FES row training (adjusted R(2)=.15, P=.10). In contrast, the relation between level of injury and peak minute ventilation was comparable before and after FES row training (adjusted R(2)=.38 vs .32, both P<.05). CONCLUSIONS: The increased aerobic capacity reflects more than increased ventilation; FES row training effectively circumvents the effect of SCI on peak aerobic capacity by engaging more muscle mass for training, independent of the level of injury.

Aerobic capacity with hybrid FES rowing in spinal cord injury: comparison with arms-only exercise and preliminary findings with regular training.

OBJECTIVE: To determine the magnitude and range of increases in peak aerobic capacity with hybrid-functional electrical stimulation (FES) rowing versus arms-only rowing in persons with spinal cord injury. DESIGN: Comparison of graded exercise tests for peak responses during FES rowing and arms-only rowing. Preliminary data on adaptations to FES row training were gathered in a subset of individuals. SETTING: Outpatient cardiovascular research laboratory. PARTICIPANTS: Six male patients with spinal cord injury (T4-T9, American Spinal Injury Association class A). METHODS OR INTERVENTION: Arms-only rowing was compared with FES rowing, in which the person who is exercising synchronizes the voluntarily controlled upper body movement with the FES-controlled leg movement via stimulation to the paralyzed leg muscles. A subgroup (n = 3) completed at least 6 months of a progressive FES row training exercise program with graded exercise tests every 6 months. MAIN OUTCOME MEASUREMENTS: Peak oxygen consumption, peak ventilation, peak respiratory exchange ratio, peak heart rate, and peak oxygen pulse. RESULTS: Peak oxygen consumption was greater during FES rowing than during arms-only rowing (20.0 ± 1.9 mL/kg/min versus 15.7 ± 1.5 mL/kg/min, P = .01). Peak ventilation was similar, whereas peak respiratory exchange ratio and peak heart rate tended to be lower (P = .14 and P = .19, respectively). As a result, oxygen pulse was greater by 35% during FES rowing. Two of the three persons who completed at least 6 months of FES row training demonstrated increases in aerobic capacity greater than those previously observed in able-bodied individuals. CONCLUSIONS: FES rowing may provide a more robust exercise stimulus for persons with spinal cord injury than most options currently available because of the greater aerobic demand.

Incongruous changes in heart period and heart rate variability with vagotonic atropine: implications for rehabilitation medicine.

OBJECTIVE: To describe the relationship between vagally mediated bradycardia and heart rate variability indices in young and older healthy individuals. DESIGN: Cross-sectional, physiologic study. SETTING: Outpatient cardiovascular research laboratory. PARTICIPANTS: A total of 34 young (mean age 24 years) and 27 older (mean age 63 years) healthy adults. METHODS: Eight bolus injections of atropine sulfate were given intravenously to participants while in a supine position (cumulative doses from 0.4 to 7.2 microg/kg). Each dose was followed by a 3-minute data collection period in which subjects controlled their breathing frequency at a rate of 15 breaths per minute. MAIN OUTCOME MEASUREMENTS: Chronotropic responses were assessed from average RR interval and blood pressure was assessed by automated brachial cuff. Heart rate variability (HRV) indices were calculated to represent both time domain measures (RR interval standard deviation and root mean squared of successive differences) and frequency domain measures (respiratory sinus arrhythmia and total power). RESULTS: RR interval responses exhibited the expected curvilinear pattern to atropine administration with all subjects exhibiting a bradycardia with at least one dose and RR interval returning to baseline or decreasing in most subjects as atropine dosing progressed. RR interval was closely related to vagotonic atropine dose with an r(2) greater than 0.70 in 89% of subjects. Heart rate variability indices were not consistently correlated with the bradycardic effect of vagotonic atropine and ranged from highly positive to highly negative with almost one-fifth of correlations less than 0.5. CONCLUSIONS: The relationship between HRV and vagal tone is likely complex and has a large interindividual variation.

Arterial baroreflex control of cardiac vagal outflow in older individuals can be enhanced by aerobic exercise training.

Maintained cardiac vagal function is critical to cardiovascular health in human aging. Aerobic exercise training has been considered an attractive intervention to increase cardiovagal baroreflex function; however, the data are equivocal. Moreover, if regular exercise does reverse the age-related decline in cardiovagal baroreflex function, it is unknown how this might be achieved. Therefore, we assessed the effects of a 6-month aerobic training program on baroreflex gain and its mechanical and neural components in older individuals (5 women and 7 men, aged 55 to 71 years). We assessed baroreflex function using pharmacological pressure changes (bolus nitroprusside followed by bolus phenylephrine) and estimated the integrated gain (Delta R-R interval/Delta systolic blood pressure) and mechanical (Delta diameter/Delta pressure) and neural (Delta R-R interval/Delta diameter) components via measurements of carotid artery diameter in previously sedentary older individuals before and after 6 months of aerobic training. There was a significant 26% increase in baroreflex gain that was directly related to the amount of exercise performed and that was derived mainly from an increase in the neural component of the arterial baroreflex (P<0.05). We did find changes in the mechanical component, but unlike integrated gain and the neural component, these were not related to the magnitude of the exercise stimulus. These results suggest that exercise training can have a powerful effect on cardiovagal baroreflex function, but a sufficient stimulus is necessary to produce the effect. Moreover, adaptations in the afferent-efferent baroreflex control of cardiac vagal outflow may be crucial for the improvement in arterial baroreflex function in older humans.

Effects of fitness and age on the response to vagotonic atropine.

Previous work indicates compromised cardiac vagal control plays a prominent role in reducing arterial baroreflex gain with age, however older fit individuals display cardiovagal baroreflex responses similar to young individuals. The purpose of this study was to test the hypothesis that chronic aerobic exercise mitigates against age-related declines in cardiac parasympathetic receptor function. In forty-four young and old (fit and unfit) individuals, we used the parasympathomimetic responses to low doses of atropine to probe cardiac cholinergic receptor responses. Data were collected before and after eight doses of atropine sulfate from 0.4 to 7.2 microg/kg. Chronotropic responses were assessed from average RR intervals and heart rate variabilities were derived in time and frequency domains. All subjects exhibited bradycardia with at least one dose of atropine and peak bradycardia occurred at a similar dose in each group. However, changes in heart rate variability did not consistently track the chronotropic responses within subjects (r-square from 0.90 down to 0). As expected, basal RR interval was longer in the fit groups and was unaffected by age. However, the degree of RR interval lengthening with parasympathomimetic atropine was unaffected by physical fitness and was significantly less in all older subjects. These data indicate there are certain prepotent age-related declines in the cardiac parasympathetic system that cannot be prevented by regular physical activity.