Functional restitution of cardiac control in heart transplant patients

Cardiovascular control is fundamentally altered after heart transplantation (HT) because of surgical denervation of the heart. The main goal of this work was the noninvasive characterization of cardiac rate control mechanisms after HT and the understanding of their nature. We obtained 25 recordings from 13 male HT patients [age = 28-68 yr, time after transplant (TAT) = 0.5-62.5 mo]. The control group included 14 healthy men (age = 28-59 yr). Electrocardiogram, continuous blood pressure (BP), and respiration were recorded for 45 min in the supine position and then during active change of posture (CP) to standing. The signals were analyzed in the time domain [mean and variance of heart rate (HR) and rise time of HR in response to CP] and the frequency domain [low and high frequency (LF and HF)]. Our principal finding was the consistent pattern of evolution of the HR response to standing: from no response, via a slow response (>40 s, TAT > 6 wk), to a fast increase (<20 s, TAT > 24 mo). HR response correlated with TAT (P < 0.001). LF correlated with HR response to CP (P < 0.0001); HF and HR did not. An important finding was the presence of very-high-frequency peaks in the power spectrum of HR and BP fluctuations. Extensive arrhythmias tended to appear at the TAT that corresponds to the transition from slow to fast HR response to CP. Our results indicate a biphasic evolution in cardiac control mechanisms from lack of control to a first-order control loop followed by partial sympathetic reinnervation and, finally, the direct effect of the old sinoatrial node on the pacemaker cell of the new sinoatrial node. There was no indication of vagal reinnervation.     

Suppression of cardiocirculatory responses to orthostatic stress by passive walking-like leg movement in healthy young men

ABSTRACT: BACKGROUND: Although passive walking-like leg movement in the standing posture (PWM) has been used in the clinical field, the safety of PWM has not been fully determined despite the risks of orthostatic intolerance due to standing posture. The aim of the present study was to examine cardiocirculatory response during PWM in healthy young men. METHODS: The subjects (n = 13) spent 5 min in a sitting position and then 5 min in a quiet standing position to determine baseline levels. Thereafter, they underwent 25-min rhythmic PWM at 1 Hz while standing. In another bout, subjects experienced the same protocol except that they underwent 25-min quiet standing (QS) instead of 25-min PWM. Two subjects dropped out of the 25-min QS due to feeling of discomfort. Thus, data obtained in the remaining eleven subjects are presented. RESULTS: In the PWM trial, systolic arterial blood pressure (SAP) decreased from 112 +/- 8 mmHg during the sitting baseline period to 107 +/- 8 mmHg during the standing baseline period (p <0.05), while heart rate (HR) increased from 73 +/- 9 bpm during the sitting baseline period to 84 +/- 10 bpm during the standing baseline period (p <0.001). After the imposition of PWM, SAP increased from 107 +/- 8 mmHg in the standing baseline period to 120 +/- 6 mmHg (p <0.001), while HR decreased from 84 +/- 10 bpm in the standing baseline period to 76 +/- 9 bpm (p <0.05). In the QS trial, SAP, which had decreased during the standing baseline period compared to that during the sitting baseline period, remained lowered during the 25-min QS period, while HR, which had increased during the standing baseline period compared to that during the sitting baseline period, remained elevated during the 25-min QS period. In both bouts, HR showed almost mirror-image changes in the high-frequency component of HR variability, suggesting that the changes in HR were due to change in parasympathetic activation. Double product (HR x SAP), as a predictor of myocardial oxygen consumption, during the 25-min QS period tended to increase with time, but double product remained almost constant during the 25-min PWM period. CONCLUSIONS: The results suggest that PWM is effective for suppressing cardiocirculatory responses to orthostatic stress.     

Arg16/Gly beta2-adrenergic receptor polymorphism alters the cardiac output response to isometric exercise.

Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic-receptor polymorphism have 1) greater forearm beta2-receptor mediated vasodilation and 2) a higher heart rate (HR) response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the higher HR response in Gly16 subjects serves to maintain the pressor response [increased cardiac output (CO)] in the setting of augmented peripheral vasodilation to endogenous catecholamines, we measured continuous HR (ECG), arterial pressure (Finapres), and CO (transthoracic echocardiography) during isometric, 40% submaximal handgrip to fatigue in healthy subjects homozygous for Gly (n = 30; mean age +/- SE: 30 +/- 1.2, 13 women) and Arg (n = 17, age 30 +/- 1.6, 11 women). Resting data were similar between groups. Handgrip produced similar increases in arterial pressure and venous norepinephrine and epinephrine concentrations; however, HR increased more in the Gly group (60.1 +/- 4.3% increase from baseline vs. 45.5 +/- 3.9%, P = 0.03), and this caused CO to be higher (Gly: 7.6 +/- 0.3 l/m vs. Arg: 6.5 +/- 0.3 l/m, P = 0.03), whereas the decrease in systemic vascular resistance in the Gly group did not reach significance (P = 0.09). We conclude that Gly16 homozygotes generate a higher CO to maintain the pressor response to handgrip. The influence of polymorphic variants in the beta2-adrenergic receptor gene on the cardiovascular response to sympathoexcitation may have important implications in the development of hypertension and heart failure.     

The influence of endurance training on the transient haemodynamic response to orthostatic manoeuvre.

Several investigations demonstrated that aerobic fitness is associated with a tendency towards orthostatic hypotension whereas other reports did not show any differences in cardiovascular adjustment to orthostatic challenges between endurance trained and sedentary subjects. In the present work, the time course of changes in heart rate (HR), systolic time intervals (STI), stroke volume (SV), cardiac output (CO) and blood pressure was studied during 8 minutes following standing up from supine position in 7 healthy volunteers before and after 10 weeks of endurance training on bicycle ergometer. Impedance cardiography was used for measurement of cardiac postural responses. The training program applied in this study increased the subjects' aerobic capacity (VO2max) by approx. 18%. After training, the steady-state supine HR and contribution of the pre-ejection period and ejection time to the total R-R interval in ECG were lowered while SV was significantly increased. No significant training-induced changes were found in magnitude and time-courses of HR, STI, SV and CO changes following standing up. Diastolic blood pressure during standing was greater after than before training. It is concluded that the short-time endurance training does not affect adversely cardiovascular orthostatic response and may even improve orthostatic tolerance due to the augmentation of diastolic blood pressure response.     

Initial cardiovascular response on change of posture from squatting to standing

The immediate cardiovascular responses on active change from the squatting (control) to the standing position differ from those obtained in the lying-to-standing manoeuvre. Without exception, the first beat after changing from squatting to standing showed a decrease in systolic, diastolic and mean pressure by 2.0 +/- 1.1 kPa (14.6 +/- 8.3 mm Hg), 1.4 +/- 1.7 kPa (10.6 +/- 12.6 mm Hg) and 1.9 +/- 1.0 kPa (13.9 +/- 7.3 mm Hg), respectively. During the 4th or 5th pulse after standing the pulse pressure was significantly higher than when lying (P less than 0.01). Mean pressure reached a minimum of 7.7 +/- 1.9 kPa (57.8 +/- 14.4 mm Hg) after 7.1 +/- 1.1 s. Thereafter the blood pressure increased to a new level within about 15 s. 11 of 16 subjects demonstrated a biphasic heart rate (HR) response. The maximum HR was reached after 11.0 +/- 2.4 s of standing. In all experiments, the peaks in HR were distinctly delayed after the blood pressure dips. We conclude that an arterial baroreflex could be implicated in the immediate HR increase after a squatting-to-standing manoeuvre. The subsequent time course of the initial HR response, however, might be induced by other mechanisms.     

Inter- and intra-individual variations of heart rate variability in Japanese males

Spectral components of heart rate variability (HRV) were repeatedly measured (4-8 measurements; mean: 6 measurements) in 75 healthy Japanese male subjects (age range: 20-61) under two postural conditions (standing and supine). Low-frequency (LF) and high-frequency (HF) components and mean heart rate (HR) were analyzed with special reference to individual variations, which were classified into two types: inter- (interV) and intra-individual variations (intraV). The percent contributions and coefficients of variations were calculated for both interV and intraV. Percent contributions of intraV (intraV%) of HR with standing and supine postures were 15.8 and 12.9%, respectively. The intraV% of HF and LF on standing were 31.5 and 26.5%, while those in the supine posture were 27.8 and 35.5%, respectively. The coefficients of interV (interCV) and intraV (intraCV) were also calculated. The interCVs of HR, HF, and LF on standing were 14.9, 41.4, and 48.4%, while those in the supine posture registered 16.2, 42.9, and 44.2%, respectively. The intraCVs of HR, HF, and LF on standing were 5.0, 19.7, and 21.2%, while those in the supine posture indicated 4.7, 20.1, and 23.0%, respectively. We also calculated the interV and intraV of logarithmic-transformed HRV indexes. The log-transformation remarkably diminished both variables: interCV and intraCV registered 14-16 and 6-7%, respectively. Although interV variations were considerably large, intraV variations of HRV were negligibly small. The HRV indexes decreased with age, although HR remained unchanged. The coefficients of determination (r2) were 14-34%. In the case of log-transformed HRV indexes, the coefficients of determination registered 9-15%, suggesting that 14-34% (raw) or 9-15% (log) of the observed interV may be due to variations in age.     

Altered autonomic cardiac regulation in individuals with Down syndrome

We tested the hypothesis that individuals with Down syndrome, but without congenital heart disease, exhibit altered autonomic cardiac regulation. Ten subjects with Down syndrome (DS) and ten gender-and age-matched healthy control subjects were studied at rest and during active orthostatism, which induces reciprocal changes in sympathetic and parasympathetic traffic to the heart. Autoregressive power spectral analysis was used to investigate R-R interval variability. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. No significant differences between DS and control subjects were observed in arterial blood pressure at rest or in response to standing. Also, R-R interval did not differ at rest. R-R interval decreased significantly less during standing in DS vs. control subjects. Low-frequency (LFNU) and high-frequency (HFNU) (both expressed in normalized units) components of R-R interval variability did not differ between DS and control subjects at rest. During standing, significant increase in LFNU and decrease in HFNU were observed in control subjects but not in DS subjects. Baroreflex sensitivity (BRS) did not differ between DS and control subjects at rest and underwent significant decrease on going from supine to upright in both groups. However, BRS was greater in DS vs. control subjects during standing. These data indicate that subjects with DS exhibit reduced HR response to orthostatic stress associated with blunted sympathetic activation and vagal withdrawal and with a lesser reduction in BRS in response to active orthostatism. These findings suggest overall impairment in autonomic cardiac regulation in DS and may help to explain the chronotropic incompetence typically reported during exercise in subjects with DS without congenital heart disease.     

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.     

Effects of three-day bed rest on metabolic, hormonal and circulatory responses to an oral glucose load in endurance or strength trained athletes and untrained subjects.

The study was designed to find out (1) whether the effect of 3-day bed rest on blood glucose (BG) and plasma insulin (IRI) responses to glucose ingestion depends on preceding physical activity and (2) whether plasma adrenaline (A), noradrenaline (NA) and cardiovascular changes following a glucose load are modified by bed rest. Eleven sedentary students (22.5+/-0.3 yrs), 8 long distance runners (18.6+/-0.3 yrs) and 10 strength trained athletes (21.2+/-2.1 yrs) were examined before and after bed rest. Plasma IRI, BG, NA, A, heart rate (HR), and blood pressure (BP) were measured during 2 hrs following glucose (75 g) ingestion. The responses of BG and IRI to glucose load were calculated as incremental areas under the curves (auc). Both in athletes and untrained subjects bed rest markedly increased IRIauc, while BGauc was elevated only in sedentary subjects (p<0.05). The greatest increases in IRIauc and IRI/BG ratios were found in the endurance athletes. The data from all subjects (n = 29) revealed that the initial plasma NA and glucose-induced increases in NA and A were lowered after bed rest (p < 0.01). These effects were most pronounced in the endurance athletes. Bed rest did not influence HR or BP in any group. It is concluded that (1) the athletes have more adequate compensation for the bed-rest-induced decrement in insulin sensitivity than sedentary men; (2) three-day bed rest diminishes basal sympathetic activity and attenuates sympathoadrenal response to oral glucose; (3) endurance athletes have greater sympathetic inhibition than strength athletes or sedentary men.     

Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise

Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF, forearm vascular conductance (FVC), leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P < 0.05). Moreover, there were significant positive linear relationships between the reduction in HR and the reductions in TVC, LVC, and FVC. We conclude that individuals who show greater apnea-induced bradycardia during exercise also show greater vasoconstriction in both active and inactive muscle regions.     

Heart rate variability following coronary artery bypass graft surgery as a function of recovery time, posture, and exercise

This study examined the claim made by Niemela et al. (1992) that the decline in heart rate variability after coronary artery bypass graft surgery is irreversible. We tested six women and 16 men six and 12 weeks postoperative in three postures: in the supine position, in the standing position, and during low-intensity steady-state exercise. Beat-by-beat arterial blood pressure and electrocardiographic R-R interval data were collected continuously for 10 min in each condition. R-R interval data were analyzed with spectral analysis; baroreflex data were analyzed using the sequence method. Our results show that the indices of parasympathetic modulation improved over time, as seen by an increased spontaneous baroreflex sensitivity and parasympathetic indicator, that both indices were affected by posture, and that spontaneous baroreflex sensitivity was also affected by low-intensity exercise. The effects of posture are consistent with attenuated responses of healthy older subjects to orthostatic stress. Similarly, the effects of low-intensity exercise are consistent with findings in healthy subjects. We found that spontaneous baroreflex sensitivity declined during exercise, whereas, in healthy subjects, this is maintained during low-intensity steady-state exercise. Our results of significant functional recovery between six and 12 weeks postoperative suggest that at least some of the autonomic dysfunction following surgery is temporary. Previously, no such duration of study has lasted longer than four or six weeks following cardiac surgery, which may not have been long enough to show significant functional restoration in heart rate variability.     

Correlations Between the Manifestations of Autonomic Regulation Related to the Orthostatic Test and Physical Loading

In 30- to 45-year-old healthy men (workers of the coal mines), we studied using correlation analysis the interrelations between the manifestations of autonomic regulation of the heart rhythm related to the active orthostatic test (AOT) and the state of systemic circulation in the physical loading test (PhLT). It has been concluded that the pattern of correlations is determined by the direction of autonomic regulatory drives within a transitional period of the AOT. In the group of tested persons with clear domination of ergotropic reactions, the variation range and power of a slow wave component of the heart rhythm in the standing posture strictly correlated with the cardial stroke, peripheral resistance, vascular tone, myocardial tension, and aerobic productivity. In persons with relatively balanced ergotropic and trophotropic effects, the AOT transitional period was characterized by correlations of nearly all indices of autonomic regulation of the heart rhythm with the indices of central hemodynamics of the PhLT.     

Heart rate recovery after maximal exercise is associated with acetylcholine receptor M2 (CHRM2) gene polymorphism

The determinants of heart rate (HR) recovery after exercise are not well known, although attenuated HR recovery is associated with an increased risk of cardiovascular mortality. Because acetylcholine receptor subtype M2 (CHRM2) plays a key role in the cardiac chronotropic response, we tested the hypothesis that, in healthy individuals, the CHRM2 gene polymorphisms might be associated with HR recovery 1 min after the termination of a maximal exercise test, both before and after endurance training. The study population consisted of sedentary men and women (n = 95, 42 +/- 5 yr) assigned to a training (n = 80) or control group (n = 15). The study subjects underwent a 2-wk laboratory-controlled endurance training program, which included five 40-min sessions/wk at 70-80% of maximal HR. HR recovery differed between the intron 5 rs324640 genotypes at baseline (C/C, -33 +/- 10; C/T, -33 +/- 7; and T/T, -40 +/- 11 beats/min, P = 0.008). Endurance training further strengthened the association: the less common C/C homozygotes showed 6 and 12 beats/min lower HR recovery than the C/T heterozygotes or the T/T homozygotes (P = 0.001), respectively. A similar association was found between A/T transversion at the 3'-untranslated region of the CHRM2 gene and HR recovery at baseline (P = 0.025) and after endurance training (P = 0.005). These data suggest that DNA sequence variation at the CHRM2 locus is a potential modifier of HR recovery in the sedentary state and after short-term endurance training in healthy individuals.     

Early autonomic malfunction in normotensive individuals with a genetic predisposition to essential hypertension

One of the primary pathologies associated with hypertension is a complex autonomic dysfunction with evidence of sympathetic hyperactivity and/or vagal withdrawal. We investigated the possibility for early detection of essential hypertension on the basis of the analysis of heart rate (HR) and blood pressure fluctuations, which reflect autonomic control. Young adult normotensive offspring of one hypertensive parent (KHT; n = 12) and normotensive offspring of two normotensive parents (YN; n = 14) participated in this study. ECG, continuous blood pressure, and respiration were recorded during steady-state conditions and under various autonomic challenges. Time-frequency decomposition of these signals was performed with the use of a continuous wavelet transform. The use of the wavelet transform enables the extension of typical HR variability analysis to non-steady-state conditions. This time-dependent spectral analysis of HR allows time-dependent quantification of different spectral components reflecting the sympathetic and parasympathetic activity during rapid transitions, such as an active change in posture (CP). During an active CP from the supine to standing position, KHT demonstrated a significantly greater increase in the low-frequency fluctuations in HR than YN, indicating enhanced sympathetic involvement in the HR response to CP, and a reduced alpha-index, indicating decreased baroreceptor sensitivity. On recovery from handgrip, vagal reactivation was more sluggish in KHT. These results indicate the early existence of malfunctions in both branches of autonomic control in individuals at increased risk of hypertension.     

Reduced forearm alpha1-adrenergic vasoconstriction is associated with enhanced heart rate fluctuations in humans.

In the present study, we assessed whether heart rate (HR) or arterial pressure fluctuations are enhanced in healthy young humans with reduced alpha-adrenergic vasoconstrictor responses and, if so, whether this occurs for both alpha1- and alpha2-adrenergic receptor-mediated vasoconstriction. Arterial pressure (brachial artery catheter) and HR (ECG) were monitored continuously, and alpha1- and alpha2-adrenergic responsiveness was determined by assessing the effects of brachial artery infusions of phenylephrine (alpha1-adrenergic agonist) and dexmedetomidine (alpha2-adrenergic agonist), respectively, on forearm blood flow (strain gauge plethysmography). alpha1-Adrenergic responsiveness varied markedly among the subjects (n=20) and was inversely correlated with coefficient of variation for HR (R2=0.37, P<0.01), whereas the responsiveness was not correlated with the coefficient of variation for either systolic or diastolic arterial pressure. alpha1-Adrenergic responsiveness was inversely and more strongly correlated with baroreflex sensitivity (R2=0.62, P<0.0001), determined from beat-to-beat changes in HR and systolic arterial pressure, than the coefficient of variation for HR. On the other hand, alpha2-adrenergic responsiveness was not correlated with any of the parameters determined above. These results suggest that, in healthy young subjects, the enhanced HR response to changes in systolic pressure helps maintain the stability of arterial blood pressure when alpha1-adrenergic responsiveness is reduced.     

Office blood pressure,heart rate and A(-596)G interleukin-6 gene polymorphism in apparently healthy Czech middle-aged population

The aim of the study was to assess the association between promoter polymorphism [A(-596)G] in interleukin-6 gene and office systolic and diastolic blood pressures, and the heart rate (HR) in apparently healthy Czech subjects. Furthermore, we evaluated the possible influence of gender, BMI and smoking on these supposed associations. An age-matched (40-50 years) and gender-matched (F/M=81/89) sample of apparently healthy Czech subjects (n=170, F/M=81/89) without hypertension, other cardiovascular diseases or diabetes was examined. The A(-596)G Il-6 gene polymorphism was detected by the PCR method. No differences in genotype distribution and/or allelic frequency was found between groups with lower systolic blood pressure (? 122 mm Hg) and higher systolic blood pressure (> 122 mm Hg). Similarly, no differences in the IL-6 polymorphism were found between lower (? 86 mm Hg) and higher (> 86 mm Hg) diastolic blood pressure groups. However, we proved a significant increase of genotypes AG+GG as well as the allele (-596)G in higher (>78 beats/min) heart rate group. The genotypes AG+GG represent significantly higher relative risk for higher HR frequency, especially in women. Among lean persons with a low heart rate frequency, fewer AG+GG genotypes were determined than among any other subjects. The genotypes AG+GG are more frequent in non-smoking persons with higher HR compared to non-smoking subjects with lower HR, especially in women. Gender, BMI and smoking substantially modify the distribution of A(-596)G Il-6 gene polymorphism in apparently healthy persons with lower or higher heart rate.     

Psychometric and comparative study of an Argentine version of the morningness composite and the early/late preference scales

This study examined the psychometric properties of an Argentine Version of the Morningness Composite (CS) and the Early/Late Preference (PS) Scales. During summer (long photoperiod in Argentina), 304 subjects (69.1% women; mean age=33.64 yrs, SD=14 yrs) completed the scales for the first time. In winter (short photoperiod), 100 of the same individuals (71% women; mean age=37.17 yrs, SD=14.63 yrs) were retested. The total scores ranged within the values reported by previous studies and were independent of gender. Older subjects showed higher morningness scores. The internal consistencies were good (CS=0.86, PS=0.82). Item 7 from the CS and items 7 and 9 from the PS showed low item-scale correlation. Factor analysis produced a three-factor solution for both scales. However, the inconsistency of the evening items suggests that the single-solution may be more acceptable. Test-retest correlations were satisfactory (CS=0.88, PS=0.78), but the two-related-sample test revealed significant differences between test and retest scores, suggesting relative temporal stabilities. Both scales presented similar and acceptable psychometric properties and good correlation, indicating construct validity.     

Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans

Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress.     

Relationships of Oxygen Consumption, Hemodynamics, and Heart Rate Variability with the Functional Class of Coronary Artery Disease Patients

The functional classes (FCs) established according to the criteria of the New York Heart Association were tested for association with oxygen consumption, the state of central hemodynamics, and heart rate (HR) variability in coronary artery disease (CAD) patients. Oxygen consumption, central hemodynamics, and HR variability at rest and during exercise were assayed in 146 CAD patients and 30 healthy individuals (the control group). It was established that the peak oxygen consumption (VO_2max), anaerobic threshold, pulmonary ventilation, systolic and minute blood volume at the threshold load (TL), and HR variability in a supine position significantly decrease and the total vascular peripheral resistance at rest and during exercise increases with increasing FC in CAD patients. The closest correlation of FC was revealed with physical working capacity, anaerobic threshold, age, and peak oxygen consumption. Moderate correlations were established with the chronotropic function of the heart at the threshold load, HR variability, the high- and low-frequency components of the cardiac rhythm at TL, pulmonary ventilation, stroke volume at rest and at TL, and the carbon dioxide ventilation equivalent at TL. In healthy individuals, the peak oxygen consumption closely correlated with the HR variability, the very low frequency component at TL, and physical capacity. With an increase in FC in CAD patients, peak oxygen consumption became more tightly associated with the chronotropic function and the hemodynamic components at TL than with the HR variability in a supine position or at TL.     

Phase-averaged characterization of respiratory sinus arrhythmia pattern

A method for the accurate time-domain characterization of respiratory sinus arrhythmia (RSA) pattern is presented and applied to two groups of healthy subjects to lay the baseline of RSA patterns and to underlay their features: response to standing, stability in successive recordings, and individuality of the shape of RSA pattern. RSA pattern is evaluated by selective averaging of heart rate (HR) changes from multiple respiratory cycles over the respiratory phase and represents the complete modulating function of HR by respiration. The RSA pattern is evaluated with free respiration and even in cases of severe arrhythmia. Estimation error is 6-8% in magnitude, phase resolution is 0.2 rad, and sensitivity margin for respiratory-related HR variability (HRV) components is 1%. RSA magnitude, phase lag, and expiration-to-inspiration time ratio are derived in addition to the entire pattern. In a group of 10 healthy young adults, a phase lag difference of 11.4 +/- 8.5% (mean +/- SD, P < 0.004) was observed between supine and standing postures, possibly ascribed to breathing mechanics. A second group of 15 healthy young adults at supine rest showed stability of the RSA pattern in successive recordings (several weeks apart) as well as individuality among subjects. This may suggest a nonscalar individual long-term index for cardiorespiratory coupling. The method is complementary to the existing statistical and spectral methods. It allows the complete characterization of the primary RSA components and may provide new insight into the effects of vagal activity and changes in clinical conditions.