Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study.

BACKGROUND: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. METHODS: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. RESULTS: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). CONCLUSION: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

Acute Hypotensive Response to Continuous and Accumulated Isocaloric Aerobic Bouts.

Evidence indicates that chronic reductions in blood pressure (BP) due to aerobic exercise depend on the ability to induce post-exercise hypotension (PEH) after each training bout. The purpose of this study was to investigate PEH after isocaloric bouts of continuous and accumulated running. 10 healthy pre-hypertensive men (aged 27.6±3.5 years) performed the following bouts of exercise: a) A continuous bout (CONT) expending a total of 400 kcal; and b) An accumulated bout split into 2×200 kcal (INTER1 and INTER2) to total 400 kcal at 75% of oxygen uptake reserve. BP, mean arterial pressure (MAP) and heart rate variability were monitored 10 min before and 60 min after control and all exercise conditions. The decrease in MAP over time after continuous (400 kcal) and accumulated (2×200 kcal) bouts of exercise was more pronounced than during control (mean diff between 1.6 and 5.4 mmHg, P≤0.01), although the magnitude of change was similar between continuous and accumulated bouts (mean diff=0.1 mmHg, P=0.79). Concomitant to the PEH, sympathovagal balance was inversely related to changes in MAP after isocaloric bouts performed continuously and cumulatively (r=- 0.72 and-0.85, P=0.019 and 0.002, respectively). In conclusion, BP decreased to similar levels after continuous and accumulated acute aerobic exercise matched for total energy expenditure. Our findings also indicate that the recovery pattern of cardiac autonomic activity may have an important role in eliciting PEH.

Cardiac autonomic dysfunction in anabolic steroid users.

This study aimed to evaluate if androgenic-anabolic steroids (AAS) abuse may induce cardiac autonomic dysfunction in recreational trained subjects. Twenty-two men were volunteered for the study. The AAS group (n = 11) utilized AAS at mean dosage of 410 ± 78.6 mg/week. All of them were submitted to submaximal exercise testing using an Astrand-Rhyming protocol. Electrocardiogram (ECG) and respired gas analysis were monitored at rest, during, and post-effort. Mean values of VO2 , VCO2 , and VE were higher in AAS group only at rest. The heart rate variability variables were calculated from ECG using MATLAB-based algorithms. At rest, AAS group showed lower values of the standard deviation of R-R intervals, the proportion of adjacent R-R intervals differing by more than 50 ms (pNN50), the root mean square of successive differences (RMSSD), and the total, the low-frequency (LF) and the high-frequency (HF) spectral power, as compared to Control group. After submaximal exercise testing, pNN50, RMSSD, and HF were lower, and the LF/HF ratio was higher in AAS group when compared to control group. Thus, the use of supraphysiological doses of AAS seems to induce dysfunction in tonic cardiac autonomic regulation in recreational trained subjects.

The effects of positive airway pressure on cardiovascular responses, perceived effort and time to exhaustion during high-intensity exercise in healthy subjects.

AIM: We investigated the effects of continuous positive airway pressure (CPAP) on the time to fatigue, rates of perceived exertion (RPE), and cardiovascular responses during sustained, high-intensity exercise (80% of VO2peak). METHODS: Healthy male subjects (N.=11) underwent CPAP adaptation at rest to exclude those who felt incapable of breathing with the device and to determine the hemodynamic-induced changes. Subjects performed two exercise sessions, pedaling at 80% of VO2peak with or without CPAP until volitional fatigue. Heart rate was measured continuously, and blood pressure and RPE were recorded every minute. RESULTS: The time to exhaustion was increased in the sessions with CPAP compared with sessions without CPAP (889±270 s vs. 689±256 sec, respectively, P=0.037). There were no differences in the cardiovascular variables at the end of the exercise sessions with or without CPAP. The RPE was lower during exercise with CPAP, but it reached maximal values similar to those observed at the end of exercise without CPAP. CONCLUSION: During sustained, high-intensity exercise (80% of VO2peak), CPAP extended the time to fatigue in healthy subjects but did not change the heart rate, blood pressure or rate pressure product. Additionally, the central and peripheral RPEs remained lower for a longer period of time during exercise with CPAP.

Preserved heart rate variability in first-degree relatives of subjects with Type 2 diabetes mellitus without metabolic disorders.

AIMS: To investigate the influence of a family history of Type 2 diabetes mellitus (T2DM) on resting heart rate variability in the absence of concomitant metabolic disorders. METHODS: We studied 55 first-degree relatives (FDRs) of subjects with T2DM and 36 control subjects without any known family history of diabetes. FDRs were recruited from a University Hospital out-patient diabetes clinic. The protocol included: oral glucose tolerance test (30, 60, 90 and 120 min after ingestion of 75 g glucose) blood glucose, plasma insulin, cholesterol and subfractions, triglycerides, leptin and C-reactive protein. Heart rate variability (HRV) at rest was determined by spectral analysis of interbeat intervals recorded during 10 min in the supine position. RESULTS: HRV was lower in FDRs compared with control subjects (P < 0.05). Multiple regression analysis identified cholesterol (P = 0.014) and triglycerides (P = 0.014) as significant independent predictors (model r = 0.40; P < 0.001) of HRV. Since FDRs had higher values for anthropometric and metabolic variables known to alter HRV, we performed an ancova adjusted for cholesterol and triglycerides and also another analysis in which the groups were comparable for anthropometric and metabolic characteristics. Comparison of FDRs and comparable control subjects revealed no significant difference in HRV (P > 0.05). CONCLUSIONS: A family history of T2DM, in the absence of concomitant metabolic disorders, does not impair heart rate variability.

Subacute effects of a maximal exercise bout on endothelium-mediated vasodilation in healthy subjects.

We evaluated vascular reactivity after a maximal exercise test in order to determine whether the effect of exercise on the circulation persists even after interruption of the exercise. Eleven healthy sedentary volunteers (six women, age 28 +/- 5 years) were evaluated before and after (10, 60, and 120 min) a maximal exercise test on a treadmill. Forearm blood flow (FBF) was measured by venous occlusion plethysmography before and during reactive hyperemia (RH). Baseline FBF, analyzed by the area under the curve, increased only at 10 min after exercise (P = 0.01). FBF in response to RH increased both at 10 and 60 min vs baseline (P = 0.004). Total excess flow for RH above baseline showed that vascular reactivity was increased up to 60 min after exercise (mean +/- SEM, before: 526.4 +/- 48.8; 10 min: 1053.0 +/- 168.2; 60 min: 659.4 +/- 44.1 ml 100 ml(-1) min(-1) . s; P = 0.01 and 0.02, respectively, vs before exercise). The changes in FBF were due to increased vascular conductance since mean arterial blood pressure did not change. In a time control group (N = 5, 34 +/- 3 years, three women) that did not exercise, FBF and RH did not change significantly (P = 0.07 and 0.7, respectively). These results suggest that the increased vascular reactivity caused by chronic exercise may result, at least in part, from a summation of the subacute effects of successive exercise bouts.

A semi-automatic computerized method to measure baroreflex-mediated heart rate responses that reduces interobserver variability.

Arterial baroreflex sensitivity estimated by pharmacological impulse stimuli depends on intrinsic signal variability and usually a subjective choice of blood pressure (BP) and heart rate (HR) values. We propose a semi-automatic method to estimate cardiovascular reflex sensitivity to bolus infusions of phenylephrine and nitroprusside. Beat-to-beat BP and HR time series for male Wistar rats (N = 13) were obtained from the digitized signal (sample frequency = 2 kHz) and analyzed by the proposed method (PRM) developed in Matlab language. In the PRM, time series were low-pass filtered with zero-phase distortion (3rd order Butterworth used in the forward and reverse direction) and presented graphically, and parameters were selected interactively. Differences between basal mean values and peak BP (deltaBP) and HR (deltaHR) values after drug infusions were used to calculate baroreflex sensitivity indexes, defined as the deltaHR/deltaBP ratio. The PRM was compared to the method traditionally (TDM) employed by seven independent observers using files for reflex bradycardia (N = 43) and tachycardia (N = 61). Agreement was assessed by Bland and Altman plots. Dispersion among users, measured as the standard deviation, was higher for TDM for reflex bradycardia (0.60 +/- 0.46 vs 0.21 +/- 0.26 bpm/mmHg for PRM, P < 0.001) and tachycardia (0.83 +/- 0.62 vs 0.28 +/- 0.28 bpm/mmHg for PRM, P < 0.001). The advantage of the present method is related to its objectivity, since the routine automatically calculates the desired parameters according to previous software instructions. This is an objective, robust and easy-to-use tool for cardiovascular reflex studies.

Spectral analyses of systolic blood pressure and heart rate variability and their association with cognitive performance in elderly hypertensive subjects.

Systolic hypertension is associated with cognitive decline in the elderly. Altered blood pressure (BP) variability is a possible mechanism of reduced cognitive performance in elderly hypertensives. We hypothesized that altered beat-to-beat systolic BP variability is associated with reduced global cognitive performance in elderly hypertensive subjects. In exploratory analyses, we also studied the correlation between diverse discrete cognitive domains and indices of systolic BP and heart rate variability. Disproving our initial hypothesis, we have shown that hypertension and low education, but not indices of systolic BP and heart rate variability, were independent predictors of lower global cognitive performance. However, exploratory analyses showed that the systolic BP variability in semi-upright position was an independent predictor of matrix reasoning (B = 0.08 ± .03, P-value = 0.005), whereas heart rate variability in semi-upright position was an independent predictor of the executive function score (B = -6.36 ± 2.55, P-value = 0.02). We conclude that myogenic vascular and sympathetic modulation of systolic BP do not contribute to reduced global cognitive performance in treated hypertensive subjects. Nevertheless, our results suggest that both systolic BP and heart rate variability might be associated with modulation of frontal lobe cognitive domains, such as executive function and matrix reasoning.

[Initial heart rate transient at dynamic exercise performed in apnea. Influence of the variation rate of previous lung volume]. / Transiente inicial de freqüência cardíaca no exercício dinâmico realizado em apnéia. Influência da taxa de variação do volume pulmonar precedente.

PURPOSE: To study the influence of inspiratory flow on the heart rate (HR) responses during the four-second exercise test (4sET) as a method to estimate cardiac vagal activity. METHODS: Fifteen healthy subjects performed the 4sET under two experimental situations: a) with maximal individual inspiratory flow (MIF) and b) with a slow inspiratory flow adjusted to reach total lung capacity in 4s (SIF). Vagal activity was estimated from B/C ratio obtained in ECG tracings, where B is the last R-R interval before the onset of exercise and C is the shortest R-R interval during exertion. RESULTS: Similar inspiratory capacities were reached, with significantly different inspiratory flows [mean (se)] [MIF = 2.23 (0.28) 1.s-1 and SIF = 0.59 (0.06) 1.s-1; t = 6.69; p < 0.0001]; as a result, it was observed a greater B/C ratio in MIF [1.36 (0.05)] as compared to SIF [1.13 (0.04); t = 4.42; p = 0.0006]. The inspiratory flow influenced HR responses in the 4sET. The biphasic transient induced by inspiration, with a HR acceleration followed by a relative bradycardia, has not been completed before exercise in the 4sET with SIF. CONCLUSION: Lower values of B/C in the 4sET with SIF seemed to be due to overlapping effects of apnea and exertion on HR during cycling. On the other hand, when the inspiration was performed at MIF, the oscillatory effect of respiration upon HR was completed before the onset of exercise. Therefore, the tachycardia observed during the 4sET performed after individual maximal inspiratory flow represents the isolated effect of dynamic exercise.

Influence of exercise modality on agreement between gas exchange and heart rate variability thresholds.

The main purpose of this study was to investigate the level of agreement between the gas exchange threshold (GET) and heart rate variability threshold (HRVT) during maximal cardiopulmonary exercise testing (CPET) using three different exercise modalities. A further aim was to establish whether there was a 1:1 relationship between the percentage heart rate reserve (%HRR) and percentage oxygen uptake reserve (%VO2 R) at intensities corresponding to GET and HRVT. Sixteen apparently healthy men 17 to 28 years of age performed three maximal CPETs (cycling, walking, and running). Mean heart rate and VO2 at GET and HRVT were 16 bpm (P<0.001) and 5.2 mL · kg(-1) · min(-1) (P=0.001) higher in running than cycling, but no significant differences were observed between running and walking, or cycling and walking (P>0.05). There was a strong relationship between GET and HRVT, with R2 ranging from 0.69 to 0.90. A 1:1 relationship between %HRR and % VO2 R was not observed at GET and HRVT. The %HRR was higher during cycling (GET mean difference=7%; HRVT mean difference=11%; both P<0.001), walking (GET mean difference=13%; HRVT mean difference=13%; both P<0.001), or running (GET mean difference=11%; HRVT mean difference=10%; both P<0.001). Therefore, using HRVT to prescribe aerobic exercise intensity appears to be valid. However, to assume a 1:1 relationship between %HRR and % VO2 R at HRVT would probably result in overestimation of the energy expenditure during the bout of exercise.

Influence of exercise modality on agreement between gas exchange and heart rate variability thresholds

The main purpose of this study was to investigate the level of agreement between the gas exchange threshold (GET) and heart rate variability threshold (HRVT) during maximal cardiopulmonary exercise testing (CPET) using three different exercise modalities. A further aim was to establish whether there was a 1:1 relationship between the percentage heart rate reserve (%HRR) and percentage oxygen uptake reserve ( % V ˙ O 2  R ) at intensities corresponding to GET and HRVT. Sixteen apparently healthy men 17 to 28 years of age performed three maximal CPETs (cycling, walking, and running). Mean heart rate and V ˙ O 2 at GET and HRVT were 16 bpm (P<0.001) and 5.2 mL·kg-1·min-1 (P=0.001) higher in running than cycling, but no significant differences were observed between running and walking, or cycling and walking (P>0.05). There was a strong relationship between GET and HRVT, with R2 ranging from 0.69 to 0.90. A 1:1 relationship between %HRR and % V ˙ O 2  R was not observed at GET and HRVT. The %HRR was higher during cycling (GET mean difference=7%; HRVT mean difference=11%; both P<0.001), walking (GET mean difference=13%; HRVT mean difference=13%; both P<0.001), or running (GET mean difference=11%; HRVT mean difference=10%; both P<0.001). Therefore, using HRVT to prescribe aerobic exercise intensity appears to be valid. However, to assume a 1:1 relationship between %HRR and % V ˙ O 2  R at HRVT would probably result in overestimation of the energy expenditure during the bout of exercise.

Cholinergic stimulation with pyridostigmine blunts the cardiac responses to mental stress.

Mental stress may induce myocardial ischemia and ventricular arrhythmia in patients with coronary artery disease, and cholinergic stimulation is a potential protective mechanism. The purpose of this study was to determine the effect of pyridostigmine bromide (PYR), a reversible cholinesterase inhibitor, on the cardiac responses to a mental stress challenge. Twelve healthy young volunteers were submitted to a mental stress test (arithmetic test) 2 hours after the oral administration of either placebo or PYR (45 mg) on two separate days, following a randomized crossover double-blind protocol. Heart rate was reduced after both placebo and PYR (p < 0.05), but the cardiac responses to the mental stress were lower with PYR (p < 0.05): mean RR interval (mean +/- SE)-placebo: 730 +/- 19 msec; PYR: 769 +/- 21 msec; Peak systolic pressure-placebo: 129 +/- 4 mmHg; PYR: 124 +/- 3 mmHg; Peak diastolic pressure-placebo: 92 +/- 3 mmHg; PYR: 89 +/- 4 mmHg; Mean rate-pressure product-placebo: 10,496 +/- 412 bpm x mmHg; PYR: 9,746 +/- 383 bpm x mmHg. In conclusion, 45 mg of pyridostigmine blunted the pressor and chronotropic responses to mental stress in healthy young subjects.

Subacute effects of a maximal exercise bout on endothelium-mediated vasodilation in healthy subjects

We evaluated vascular reactivity after a maximal exercise test in order to determine whether the effect of exercise on the circulation persists even after interruption of the exercise. Eleven healthy sedentary volunteers (six women, age 28 ± 5 years) were evaluated before and after (10, 60, and 120 min) a maximal exercise test on a treadmill. Forearm blood flow (FBF) was measured by venous occlusion plethysmography before and during reactive hyperemia (RH). Baseline FBF, analyzed by the area under the curve, increased only at 10 min after exercise (P = 0.01). FBF in response to RH increased both at 10 and 60 min vs baseline (P = 0.004). Total excess flow for RH above baseline showed that vascular reactivity was increased up to 60 min after exercise (mean ± SEM, before: 526.4 ± 48.8; 10 min: 1053.0 ± 168.2; 60 min: 659.4 ± 44.1 ml 100 ml-1 min-1 . s; P = 0.01 and 0.02, respectively, vs before exercise). The changes in FBF were due to increased vascular conductance since mean arterial blood pressure did not change. In a time control group (N = 5, 34 ± 3 years, three women) that did not exercise, FBF and RH did not change significantly (P = 0.07 and 0.7, respectively). These results suggest that the increased vascular reactivity caused by chronic exercise may result, at least in part, from a summation of the subacute effects of successive exercise bouts.

A semi-automatic computerized method to measure baroreflex-mediated heart rate responses that reduces interobserver variability

Arterial baroreflex sensitivity estimated by pharmacological impulse stimuli depends on intrinsic signal variability and usually a subjective choice of blood pressure (BP) and heart rate (HR) values. We propose a semi-automatic method to estimate cardiovascular reflex sensitivity to bolus infusions of phenylephrine and nitroprusside. Beat-to-beat BP and HR time series for male Wistar rats (N = 13) were obtained from the digitized signal (sample frequency = 2 kHz) and analyzed by the proposed method (PRM) developed in Matlab language. In the PRM, time series were low-pass filtered with zero-phase distortion (3rd order Butterworth used in the forward and reverse direction) and presented graphically, and parameters were selected interactively. Differences between basal mean values and peak BP (deltaBP) and HR (deltaHR) values after drug infusions were used to calculate baroreflex sensitivity indexes, defined as the deltaHR/deltaBP ratio. The PRM was compared to the method traditionally (TDM) employed by seven independent observers using files for reflex bradycardia (N = 43) and tachycardia (N = 61). Agreement was assessed by Bland and Altman plots. Dispersion among users, measured as the standard deviation, was higher for TDM for reflex bradycardia (0.60 ± 0.46 vs 0.21 ± 0.26 bpm/mmHg for PRM, P < 0.001) and tachycardia (0.83 ± 0.62 vs 0.28 ± 0.28 bpm/mmHg for PRM, P < 0.001). The advantage of the present method is related to its objectivity, since the routine automatically calculates the desired parameters according to previous software instructions. This is an objective, robust and easy-to-use tool for cardiovascular reflex studies.