Effects of Menstrual Cycle on Cardiac Autonomic Innervation As Assessed By Heart Rate Variability

Objective: The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Methods: Forty‐three nonobese regularly cycling women (age 29 ± 6, range 20–38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 ± 1 days and luteal phase 21 ± 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04–0.15 Hz), high frequency peak (HF, 0.15–0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. Results: The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 ± 1.5 vs 1.6 ± 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. Conclusion: We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation. A.N.E. 2002;7(1):60–63     

Effects of Cimetidine on Sinus Node Function and Atrioventricular Conduction in Man

Electrophysiological effects of H2-receptor blockade 200 mg cimetidine IV on sinus node (SN) function and atrioventricular (AV) conduction were evaluated. Tests were performed in 21 people in basal state (group I), and in 14 people (group II) after autonomic blockade (AB) (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). We analyzed sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and secondary pause (SP) as the longest sinus pause after incremental overdrive pacing, sinoatrial conduction time (Strauss method) (SACT), Wenckebach point (WP), and blood pressure (BP). In group I, cimetidine prolonged SCL (717 ± 98 vs 860 ± 138 msec P < 0.001), SNRT (1161 ± 153 vs 1263 ± 163 msec P < 0.002), SP (943 ± 183 vs 1072 ± 187 msec P < 0.001), SACT (121 ± 20 msec vs 149 ± 21 msec P < 0.002), and lowered rate at which AV nodal Wenckebach point were observed (169 ± 24 vs 160 ± 26 beats/min P < 0.02). The drug did not produce significant change of the CSNRT (439 ± 121 vs 402 ± 107 msec. In group II, after AB cimetidine prolonged SCL (643 ± 79 vs 656 ± 86 msec P < 0.05), SP (686 ± 114 vs 717 ± 109 msec P < 0.05) and lowered WP (170 ± 19 vs 166 ± 19 beats/min P < 0.02) significantly. The effects of cimetidine, after AB on SNRT (894 ± 180 vs 920 ± 164 msec, CSNRT (243 ± 99 vs 255 ± 85 msec), SACT (85 ± 20 msec vs 90 ± 22 msec) were not significant. We conclude that H2-receptor blockade decreases SN automatically, prolongs SACT and AV conduction in man. The study suggests that histamine takes part in regulation of electrophysiological properties of the human heart in vivo.     

Gender Differences in the Clinical Characteristics and Atrioventricular Nodal Conduction Properties in Patients With Atrioventricular Nodal Reentrant Tachycardia

Gender Differences in Patients With AVNRT. Introduction: The detailed electrophysiological characteristics of the gender differences associated with atrioventricular nodal reentrant tachycardia (AVNRT) have not been clarified. This study investigated the gender‐related electrophysiological differences in a large series of patients undergoing radiofrequency catheter ablation. Methods and Results: A total of 2,088 consecutive AVNRT patients (men/women 869/1,219) who underwent catheter ablation were enrolled in this study. We evaluated the gender differences in their electrophysiological characteristics. Women had a significantly younger age of onset, higher incidence of multiple jumps, shorter AH interval, atrial effective refractory period (ERP), anterograde fast pathway ERP, anterograde slow pathway ERP, and retrograde slow pathway ERP, and longer ventricular ERP than men. The incidence of baseline ventriculoatrial dissociation was lower in women than in men. Women needed less isoproterenol/atropine to induce AVNRT. No gender differences in the radiation exposure time, procedure time, complication rate, acute success rate, or second procedure rate were noted. Both typical and atypical AVNRT were more predominant in women. In the patients with atypical AVNRT, there was no significant gender difference in incidence of baseline ventriculoatrial dissociation; however, the retrograde slow pathway ERP was significantly shorter in women than in men. Women of premenopausal age (≤50 years old) had a significantly higher incidence of anterograde multiple jumps and a retrograde jump phenomenon, and a shorter anterograde slow pathway ERP and retrograde slow pathway ERP than those of women over 50 years old. Conclusion: Gender differences in the anterograde and retrograde AV nodal electrophysiology were noted in the patients with AVNRT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1114‐1119)     

Independent Autonomic Modulation of the Human Sinus and AV Nodes: Evidence From Beat-to-Beat Measurements of PR and PP Intervals During Sleep

Autonomic Modulation of Sinus and AV Nodes. Introduction : Evidence from animal experiments indicates that the autonomic nervous system may influence the sinus (SA) and atrioventricular (AV) nodes differently. We investigated, therefore, whether there are spontaneous functional differences in the innervation of the SA and AV nodes in man.
Methods and Results : This study was performed in 10 healthy males (ages 21 to 26 years) during strict bed rest from 10 pm to 6 am. Three ECG leads were digitized on-line. PR and PP intervals were determined on a heat-to-beat basis off-line using a correlation algorithm with an accuracy of ± 2 msec and were verified visually. During; major body movements, there were sudden decreases in PP intervals of 36 to 827 msec (mean 335) for periods of 6 to 265 seconds (mean 24), During these phases of heart rate (HR) acceleration, PR intervals showed either concomitant shortening (9 to 30 msec), no change, or lengthening (6 to 25 msec). Furthermore, tonic changes in the PR interval occurred over 15-minute periods during which the range of PP intervals was constant. Additionally, recovery-adjusted PR interval (PR - b₂/RP) and cycle length were negatively correlated for some periods, which confirmed independent autonomic effects on SA node and A V node.
Conclusion : Beat-to-beat measurement of PR intervals allows for evaluation of autonomic effects on the human AV node. The different patterns in PR intervals during sudden spontaneous increases in HR and the tonic changes in PR interval indicate that the autonomic inputs to the SA and AV nodes are, in principle, independent of each other.     

Developmental Effects of d-Sotalol on Anterograde and Retrograde Atrioventricular Conduction in the Rabbit

Developmental Electrophysiology of d-Sotalol. Introduction : These experiments investigate the developmental effects of d-sotalol on standard electrophysiologic parameters of anterograde and retrograde AV conduction in the rabbit.
Methods and Results: Using bipolar electrograms and standard pacing techniques, the effects of graded concentrations of d-sotalol on anterograde and retrograde conduction in mature and immature perfused rabbit hearts were compared. Also, a quantitative assessment of the drug's effects on a rate-dependent property of anterograde AV node (AVN) conduction, termed the "recovery process," was compared in mature and immature rabbit hearts. The main developmental electrophysiologic findings of this investigation are: (1) in both the mature and immature rabbit heart, d-sotalol increases the anterograde conduction time and prolongs refractoriness of the AVN, yet the minimal concentrations of d-sotalol that produce these changes are lower in the neonate; (2) d-sotalol increases the anterograde refractory period of the His-Purkinje system in both age groups, but increases anterograde infra-Hisian conduction only in the neonate; (3) 1 × 10⁻⁴ M d-sotalol significantly changes the time constant of the AVN recovery process in the neonate, hut not in the adult; (4) for retrograde conduction, slow conduction through the AVN (HA_max) and infra-Hisian region (VH_max) are increased by d-sotalol in the neonate, but not in the adult.
Conclusions: The findings of this study illustrate that d-sotalol has different effects on parameters of the developing AV conduction system. This implies that there may he maturational changes in the ionic currents that are responsible for anterograde and retrograde AVN and His-Purkinje conduction.     

Nighttime Differential Autonomic Modulation of Sinus and Idioventricular Automaticity and of Atrioventricular Nodal Conduction

Background: Potential differential effects of the autonomous nervous system on sinus node and protected idioventricular automaticity and on atrioventricular nodal conduction have not been assessed in the same patients. Methods: The sinus cycle lengths, parasystolic cycle lengths, uncorrected QT intervals, and PR intervals were measured in control epochs and epochs of transient spontaneous maximal nighttime heart rate accelerations occurring between 1 and 4 AM. Noncontiguous epochs were selected to avoid potential accommodation-like, or memory effects that could occur at the moments of abrupt acceleration or decelerations of sinus rate. Results: The longest sinus cycle lengths coincided with the longest parasystolic cycle lengths and uncorrected QT intervals, whereas the shortest sinus cycle lengths coexisted with the shortest parasystolic cycle lengths and the shortest QT intervals. In contrast, the PR intervals did not show a uniform behavior during the episodes of transient heart rate accelerations since they could increase, decrease, or remain the same. Conclusion: The different behavior of cycle lengths and PR intervals during nighttime heart rate increases, suggests that the autonomic modulation of the sinus node, idioventricular focus, and the AV node can be independent from each other. A.N.E. 1999;4(4):385–390     

Preserved Autonomic Modulation of the Sinus and Atrioventricular Nodes Following Posteroseptal Ablation for Treatment of Atrioventricular Nodal Reentrant Tachycardia

Autonomic Control of the AV Node. Introduction : Following radiofrequency catheter ablation of AV nodal reentrant tachycardia (AVNRT), inappropriate sinus tachycardia may occur, possibly due to damage to autonomic cardiac nerve fibers. Furthermore, inducibility of AVNRT is often critically dependent on the autonomic balance. We investigated whether successful ablation of AVNRT is associated with an alteration of autonomic input to the sinus and AV nodes.
Methods and Results : To estimate changes in the automatic modulation of the sinus and AV nodes, power spectra of beat-to-beat PP and PR intervals were analyzed from high-quality nighttime ECG recordings of 11 patients before and after radiofrequency application. Normalized HF power (nHF) of PP and PR intervals was used as an index of efferent vagal modulation and the LF/HF ratio as an index of sympathovagal balance of the sinus node (PP) and AV node (PR). Before ablation, LF/HF_PP was 3.2 and nHF_PP was 0.3 in the sinus node, For the A/V node, LF/HF_PR was 1.2 and nHF^PR was 0.5. Following ablation. LF/HF_PP (3.5) and nHF_PP (0.3) of the PP intervals did not change. Similarly to the sinus node, there were no changes in the autonomic modulation of the AV node, as both LF/HF_PR (1.2) and nHF_PR (0.5) remained unchanged.
Conclusion : Our results indicate that autonomic control of the sinus und AV nodes is preserved following successful radiofrequency ablation of AVNRT. The effects of posteroseptal radiofrequency current application are not necessarily mediated by changes in the autonomic input to the AV node.     

Different Effects of Flecainide on Atrioventricular Conduction Properties in the Adult and Immature Rabbit Heart

The influence of flecainide (0.1, 0.5, 1.0, and 2.0 µg/mL)on atrioventricular (AV) conduction was studied in neonatal and adultperfused rabbit hearts using extracellular bipolar surface electrograms andpremature atrial and ventricular pacing. Flecainide produced a concentrationand rate-related increase in the steady-state nodal conduction(AH_min and an increase in slow AH conduction(AH_max) in both age groups. The drug produced significantincreases in the refractory periods of the atrium, AV node, His-Purkinjesystem, and ventricular myocardium. The neonatal refractory periods weresignificantly greater at lower or the same drug concentrations than those ofthe adult. The neonatal Wenckebach cycle length was significantly greaterwith a lower concentration of drug (0.5 µg/mL) than was the adultWenckebach cycle length. The His-Purkinje system steady-state conductiontime (HV_min was increased by a lower concentration of drug inthe neonate (0.5 µg/mL) as compared with 2.0 µg/mL inthe adult. These data show that across a wide range of AV conductionparameters, the neonatal preparations responded to a lower concentration offlecainide than did the adult preparations. These findings may, in part, bethe basis for the reported greater efficacy of the drug in children than inadults.     

Effects of thoracic spinal cord stimulation on cardiac autonomic regulation of the sinus and atrioventricular nodes

INTRODUCTION: Thoracic spinal cord stimulation (SCS) has been used to treat angina pectoris and to produce cardiac autonomic control. We studied the effect of thoracic SCS on sinus node and AV nodal function to test the hypothesis that SCS modulated autonomic regulation of the electrophysiology of these structures. METHODS AND RESULTS: The effects of thoracic SCS on sinus cycle length and AH interval were studied in 47 dogs in five experimental groups: group 1: intact autonomic nerves; group 2: bilateral ansae subclaviae transection and efferent stellate stimulation; group 3: ansae transection, bilateral vagi transection, and efferent stellate stimulation; group 4: bilateral vagi transection and efferent vagal stimulation; and group 5: bilateral vagal stimulation and bilateral ansae subclaviae transection. Under fluoroscopic guidance, the spinal stimulator electrode was advanced to the T1-T2 position and threshold determined by adjusting the output to produce muscle contraction. Parameters were measured at baseline prior to SCS and during SCS, at 90% threshold. Ansae subclaviae and vagi nerves were isolated using standard approaches. Stellate and vagal stimulation were each performed using a constant current stimulator and at three different frequencies. Sinus cycle length and AH intervals (the latter at constant right atrial pacing of 400 msec) were measured with and without SCS at baseline and at each level of nerve stimulation. Nitric oxide was measured using the coronary sinus overflow method, from a luminal balloon catheter placed deep in the coronary sinus. SCS resulted in an increase in sinus cycle length from 507 +/- 23 msec to 544 +/- 22 msec (P = 0.02) and AH interval from 71 +/- 4 msec to 74 +/- 4 msec (P = 0.03). Ansae subclaviae transection had no effect on this increase, while vagal transection eliminated the increase in sinus cycle length and AH with SCS. The increase in these parameters with SCS was maintained during both stellate stimulation (group 2) and vagal stimulation (group 5) across all three levels of neural stimulation. CONCLUSION: SCS appears to enhance parasympathetic activity, mediated via the vagus. This may have implications for use of thoracic SCS to treat chronic angina and perhaps prevent sudden cardiac death.     

Changes in Autonomic Activity Preceding Onset of Nonsustained Ventricular Tachycardia

Background: The triggering role of the autonomic nervous system in the initiation of ventricular tachycardia has not been established. To investigate the relationship between changes in autonomic activity and the occurrence of nonsustained ventricular tachycardia (NSVT) we examined heart rate variability (HRV) during the 2-hour period preceding spontaneous episodes of NSVT. Twenty-four subjects were identified retrospectively as having had one episode of NSVT during 24-hour Holter ECG recording. Methods: We measured the mean interval between normal beats (meanRR), the standard deviation of the intervals between beats (SD), the percentage of counts of sequential intervals between normal beats with a change of >50 ms (%RR50), the logarithms of low- and high-frequency spectral components (InLF, InHF) of HRV for sequential 10-minute segments preceding NSVT. The correlation dimension (CDim) of HRV was calculated similarly for sequential 20-minute segments. We assessed the significance of the time-course change of each marker over the 120-minute period prior to NSVT onset. Results: MeanRR (P < 0.05), InLF (P < 0.0001), InHF (P < 0.0001), the natural logarithm of the ratio of LF to HF (ln[LF/HF]; P < 0.05), and CDim (P < 0.05) showed significant time-course changes during that period, while SD and %RR50 did not. MeanRR, InLF, InHF, and CDim all decreased prior to the onset of NSVT, whereas ln(LF/HF) increased. We divided the subjects into two groups: one consisting of 12 patients with coronary artery disease; and the second group of 12 patients without known coronary artery disease. Both groups showed significant changes (P < 0.05) of CDim, InLF, and InHF preceding the episodes of NSVT. Conclusions: Changes in the pattern of HRV prior to the onset of episodes of NSVT suggest that changes in autonomic activity may commonly play a role in the triggering of spontaneous episodes of NSVT in susceptible patients. The measured changes suggest a reduction in parasympathetic activity, perhaps in conjunction with an increase in sympathetic activity, may trigger NSVT.     

Atrioventricular node ablation and pacemaker implantation for recurrent syncope in a patient with postural tachycardia syndrome (POTS)

Ablate and pace for POTS. A 42-year-old woman with postural tachycardia syndrome (POTS) was admitted to our hospital with severe palpitations, light-headedness, and syncope. Several drugs had been administered previously, but all had been discontinued due to intolerable adverse effects or limited efficacy. One of the drugs, the I(f) current inhibitor ivabradine, effectively slowed the patient's heart rate and relieved the symptoms, but was discontinued due to allergy. After unsuccessful sinus node ablation, atrioventricular node ablation and dual chamber pacemaker implantation was performed, which dramatically improved her symptoms and eliminated syncope. Atrioventricular node ablation could modify the cardiac autonomic balance and thereby suppressed the excessive orthostatic sympathetic activity.     

The Frequency-Dependent Effects of Verapamil on Antegrade Refractory Periods and Conduction in the Atrioventricular Node in Man

Frequency-Dependent Effects of Verapamil. Introduction: The purpose of this study was to examine the frequency-dependent effects of verapamil on refractoriness and development of conduction block in the human atrioventricular (AV) node. Methods and Results: To more closely simulate conditions thai would be found when the drug is used clinically, the drug was assessed in the absence of autonomic blockade. Antegrade refractory periods were determined in nine patients before and during the administration of verapamil by constant intravenous infusion. In addition, continuous recordings were made during 30-second sequences of atrial pacing at a long cycle length alternating with sequences at shorter pacing cycle lengths. Mean verapamil levels were constant throughout the study and averaged 111.6 ± 70.7 ng/mL. In the majority of patients, refractoriness in the atrium prevented determination of the effective refractory period of the AV node in the control state. Therefore, although the effective refractory period of the AV node lengthened with decrease in pacing cycle length in the presence of verapamil, the relative contribution of the change in cycle length itself compared to the effect of verapamil could not be determined. A frequency- and time-dependent change in A-H interval was found with verapamil during atrial pacing. Kinetic analysis of drug effect on AV nodal function was possible in only three patients; in these three patients the mean time constant for onset of block was 2.9 seconds (range 1.9–4.0 sec). In one patient at a pacing cycle length that did not result in second-degree AV block, transient periods of alternation between short and long A-H intervals occurred in the presence of verapamil. Conclusion: Verapamil causes frequency-dependent block of conduction through the AV node. Since changes in autonomic tone will vary from patient to patient, the actual magnitude of the effects of verapamil will vary as well. This may account for some of the interpatient variability seen with clinical use of this drug, despite comparable blood levels. (J Cardiovasc Electrophysiol, Vol. 3, pp. 21–33, February 1992)     

Heart Rate and Heart Rate Variability in Normal Young Adults

Heart Rate and Heart Rate Variability. Introduction: The relationships between heart rate (HR) and HR variability (HRV) are not simple. Because both depend on the autonomic nervous system (ANS), they are not independent variables. Technically, the quantification of HRV is influenced by the duration of the cardiac cycles. The complexity of these relationships does not justify ignoring HK when studying HRV, as frequently occurs. Methods and Results: Using spectral and nonspectral methods, the HR and various normalized and non-normalized indices of HRV were studied in 24-hour recordings of a homogeneous cohort of seventeen 20-year-old healthy males. The HR-HRV relationships were appraised by analyzing the same data in two different ways. The 24 mean hourly values provide consistent information on the circadian behavior of the indices, while the average 24-hour individual data show a wide spectrum of normality. Combined approaches allow assessment of the direct impact of RR interval on HRV evaluation. The correlations between HR and normalized indices of HRV arc weaker in 24-hour individual data than in pooled hourly data of the same individuals. These correlations are close to 1 in the latter case, which does not mean that measuring HRV is simply another method of evaluating HR, but that normal physiology supposes a harmonious behavior of the various indices. When considered individually without normalization, the specific indices of vagal modulation (high-frequency band of the spectrum, short-term HR oscillations of the nonspectral analysis) consistently increase at night and diminish during the day. However, the low-frequency power, which supposedly reflects sympathetic influences, also increases at night, whereas more logically the longer HR oscillations would predominate during the day. Moreover, the selective analysis of HR oscillations during HR acceleration or decrease indicates that their behavior differs accordingly. Conclusion: We recommend that closer attention be paid to the complex relationships between HR and HRV. The strong correlations found in healthy subjects may reflect either the physiological harmony of ANS functions or simple redundancy. Their tendency to deteriorate in diseased hearts suggests that redundancy is not the cause and that abnormalities of ANS functions are not demonstrated by HRV analysis alone.     

The Effects of Sympathetic Imbalance on the Canine T Wave and QT Interval

The effects of sympathetic imbalance with left dominance on the electrocardiogram was studied in 12 open-chest anesthetized dogs. Heart rate was held constant (80 or 150 bpm) by right vagal stimulation and atrial pacing, To minimize vagai-sympathetic interactions, the intensity of vagal stimulation was well below the threshold for asystole. Electrocardiographic recordings were obtained from three ECC leads (II, X, and Z). Transection of the right stellate increased the T-wave amplitude in lead II (0.12 ± 0.05 mV, P < 0.05) but had no effect on the QT interval in any lead. Left stellate transect ion after right transection decreased the T-wave amplitude in lead II (0.13 ± 0.06 mV, P < 0.05) but did not alter the QT interval in any lead. Electrical stimulation of the decentralized left stellate for periods of 3 or 15 sec prolonged the QT interval by as much as 21 msec, but the average changes were considerably less (± 6.0 msec) and were not significant. Left stellate stimulation for 30 or 60 seconds shortened the QT by as much as 30 msec (P < 0.05). All periods of left stellate stimulation significantly increased the T-wave amplitude in lead II. The electrocardiographic changes induced by sympathetic imbalance were similar at both heart rates. The results do not support the presence of a significant degree of "silent" repolarization after the end of the T wave in the normal canine electrocardiogram.     

Influence of aging and other cardiovascular risk factors on baroreflex sensitivity

OBJECTIVES: To examine the influence of known cardiovascular risk factors (cholesterol, blood glucose levels, arterial pressures, heart rate, and aging) on baroreflex sensitivity. DESIGN: An observational epidemiological study. SETTING: Geriatric Division at the Policlinico Umberto Primo, University of Rome La Sapienza. PARTICIPANTS: Two hundred three subjects whose ages ranged from 9 to 94 years, apparently healthy and free of detectable clinical evidence of atherosclerosis. MEASUREMENTS: All subjects underwent determination of baroreflex sensitivity by phenylephrine infusion (BSphe), and by a noninvasive method derived from spectral analysis of R-R interval and arterial pressure variabilities (alpha index). RESULTS: The population, subdivided into tertiles for each variable studied, had lower BSphe values and lower alpha indexes as a function of age, plasma low-density lipoprotein (LDL) cholesterol, and systolic blood pressure. The alpha index was significantly lower in both groups with elevated LDL cholesterol levels than in those with lower levels (II and III vs I tertile, P <.001), whereas BSphe differed significantly only in the two groups who had extreme levels of LDL (I vs III tertile, P <.001). Multiple regression analysis identified a negative association of the alpha index with age (P <.001), heart rate (P <.01), area under the glucose-response curve (P <.001), and LDL cholesterol (P <.01), but of BSphe only with age (P <.001) and heart rate (P <.01). CONCLUSION: These findings indicate that some risk factors for coronary heart disease adversely influence baroreflex sensitivity.     

Does the autonomic nervous system play a role in the development of insulin resistance? A study on heart rate variability in first‐degree relatives of Type 2 diabetes patients and control subjects

AIMS: To investigate dysregulation of the autonomic nervous system as a potential mechanism for early insulin resistance in the development of Type 2 diabetes. METHODS: Thirteen healthy individuals with first-degree relatives with Type 2 diabetes (R) were compared with 14 control subjects without family history of diabetes (C), matched for age, body mass index and sex. An oral glucose tolerance test and a hyperinsulinaemic euglycaemic clamp were performed. Analysis of heart rate variability during rest, controlled breathing, an orthostatic manoeuvre and a standardized physical stress (cold pressor test (CPT)), were used to evaluate the activity of the autonomic nervous system. RESULTS: Fasting blood glucose, HbA1c and serum insulin were similar in the R and C groups. The M-value, reflecting insulin sensitivity, did not differ significantly between the groups. Total spectral power and high-frequency power were lower in R during controlled breathing (P = 0.05 and P = 0.07, respectively), otherwise there were no significant differences between R and C in heart rate variability. However, low-frequency (LF)/high-frequency (HF) spectral power ratio during CPT, reflecting sympathetic/parasympathetic balance, was negatively associated with insulin sensitivity (r = -0.53, P = 0.006). When all subjects were divided into two groups by the mean M-value, the low M-value group displayed an overall higher LF/HF ratio (P = 0.04). HF power was lower in the low M-value group during controlled breathing and CPT (P = 0.01 and P = 0.03, respectively). CONCLUSION: An altered balance of the parasympathetic and sympathetic nervous activity, mainly explained by an attenuated parasympathetic activity, might contribute to the development of insulin resistance and Type 2 diabetes.