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Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder.

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.

Adult↗

Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction.

BACKGROUND: Brain serotonin is known to possess sympathoinhibitory properties. The aim of this clinical physiologic study was to determine whether sertraline, a selective serotonin reuptake inhibitor, facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infarction (MI) in patients with depression. METHODS AND RESULTS: Thirty-eight post-MI depressed patients were randomized to receive either sertraline 50 mg per day or placebo for 6 months. Depression was defined as a score >15 on the standardized Inventory to Diagnose Depression questionnaire taken at prehospital discharge and again within 2 weeks of the acute infarct. Eleven stable post-MI nondepressed patients served as a nonrandomized reference group during follow-up. Twenty-seven patients completed the randomization. All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability (HRV) indices at baseline (1-2 weeks after MI) and at 6, 10, 14, 18, and 22 weeks. The rate of recovery of HRV was determined by use of a growth curve model based on repeated-measures analysis of variance. There was a linear rate of increase in the SD of 24-hour N-N intervals (SDNN) in the sertraline-treated group that paralleled that of the nondepressed reference group. This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks (t = 2.10, P <.05). However, the short-term power spectral indices, while trending toward a more rapid rate of recovery in the treated group, did not reach statistical significance compared with the placebo group. CONCLUSION: In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN, a recognized predictor of clinical outcome.

Acute Disease↗

Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes.

OBJECTIVE: To assess diurnal cardiac sympathetic and parasympathetic nerve functions in diabetic subjects with variable diabetic neuropathy. RESEARCH DESIGN AND METHODS: Frequency domain analysis of 24-h Holter ECG was done for 132 diabetic subjects (84 without any symptomatic neuropathy; 37 with only symptomatic peripheral neuropathy; 11 with symptomatic autonomic neuropathy) and 57 normal volunteers to calculate the low frequency (LF) component representing the beta-adrenoceptor function and the high frequency (HF) component representing the cardiac parasympathetic nerve function. RESULTS: Cardiac LF and HF components in diabetic subjects without peripheral neuropathy showed values comparable to those of normal volunteers and a similar circadian rhythm. Diabetic subjects with peripheral neuropathy or autonomic neuropathy showed significantly depressed LF and HF components and loss of the circadian rhythm of LF and HF components compared with diabetic subjects without neuropathy. Impairment of the LF component in the afternoon could be accounted for by the duration of diabetes and elevated HbA1c level. Impairment of the HF component at night could be accounted for by the duration of diabetes but not an elevated HbA1c level. CONCLUSIONS: These data indicated that diabetic subjects with peripheral neuropathy and diabetic subjects with symptomatic autonomic neuropathy, but not diabetic subjects without neuropathy, showed a marked decrease in cardiac sympathetic and parasympathetic nerve functions and loss of circadian rhythm.

Adult↗

Influence of nutrients on cardiac autonomic function in nondiabetic overweight subjects.

The current study sought to determine whether there is a link between cardiac autonomic dysfunction and food intake in overweight subjects. One hundred five nondiabetic overweight (body mass index >27 kg/m2) subjects were studied. Heart rate variations were analyzed during 3 bedside standard tests investigating mainly vagal control: deep breathing, lying-to-standing, and Valsalva tests. The resting metabolic rate and substrate oxidation rates were measured by indirect calorimetry. Dietary intake was estimated from a 3-day recall of food intake. Cardiac parasympathetic dysfunction (PSD) was found in 39 subjects. The sex ratio, age, anthropometric parameters, biochemical parameters and insulin resistance index, resting metabolic rate, and substrate oxidation rates did not differ in the subjects with or without PSD. The total 24-hour energy intake was similar, but the carbohydrate intake was significantly higher in the subjects with PSD (P = .006), and the fat and protein intakes were significantly lower (P = .026 and .045, respectively). In the logistic regression analyses, PSD correlated with carbohydrate and fat intake, independently of serum insulin levels. Glucose oxidation rate correlated negatively with fasting and postglucose serum insulin levels only in the subjects with PSD (P = .006 and .005, respectively). Cardiac parasympathetic dysfunction is associated with higher carbohydrate intake and lower fat and protein intakes in overweight subjects. A sympathetic override may contribute to reducing the glucose oxidation rate in subjects with PSD.

Adolescent↗

123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function.

PURPOSE: To investigate the influence of diabetic myocardial damage (suspected myocardial damage; SMD) diagnosed by 201Tl-SPECT and diabetic cardiac autonomic neuropathy (AN) on myocardial MIBG uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM). SUBJECTS AND METHODS: Eighty-seven diabetic patients divided into four subgroups: 23 with SMD (+) AN (+); 19 with SMD (+) AN (-); 27 with SMD (-) AN (+); 18 with SMD (-) AN (-), and 10 controls were studied. Both planar and SPECT images were taken at 30 minutes (early) and 3 hours (delayed) after 123I-MIBG injection. The heart to mediastinum uptake ratio (H/M) and washout ratio of 123I-MIBG (WR) were obtained from both planar images. On SPECT images, the total uptake score (TUS) was obtained by the 5 point score method by dividing the myocardium into 20 segments on visual analysis. Similarly, the difference between the 201Tl image and the 123I-MIBG image in TUS was taken as the difference in the total uptake score (delta TUS) representing cardiac sympathetic denervation without SMD. RESULTS: On both early and delayed planar images, the mean H/M value in the subgroups of diabetic patients was significantly lower in the SMD (+) AN (+) group than in the control group, but among those subgroups, there was statistically significant difference between the SMD (+) AN (+) and SMD (-) AN (-) groups only on the delayed images. Regarding the WR value, there was no statistically significant difference among subjects. On SPECT image analysis, the diabetic subgroup with AN or SMD had statistically significant lower values for TUS than those of the control group. Among diabetics, there was a statistically significant differences between SMD [+] AN [+] and SMD [-] AN [-] on both early and delayed images. Similarly, the SMD [+] AN [-] group also had significantly lower values than those of SMD [-] AN [-] on early images. Regarding delta TUS, there was a statistically significant differences between AN [+] subgroups and controls. Similarly, the mean value for delta TUS was much higher in AN [+] subgroups than in AN [-] subgroups with or without SMD in diabetes mellitus. CONCLUSION: 123I-MIBG myocardial uptake is affected by both SMD and cardiac autonomic neuropathy. Based on the finding that delta TUS was much higher in AN [+] subgroups and there was no statistically significant difference between SMD [+] AN [+] and SMD [-] AN [+] subgroups, a decrease in myocardial 123I-MIBG uptake might progress independently of SMD.

3-Iodobenzylguanidine↗

Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study.

Cardiac autonomic activity, as assessed by heart rate variability, has been found to be associated with postmyocardial infarction mortality, sudden death, and all-cause mortality. However, the association of heart rate variability and the incidence of coronary heart disease (CHD) is not well described. The authors report on the association of baseline cardiac autonomic activity (1987-1989) with incident CHD after 3 years (1990-1992) of follow-up of the Atherosclerosis Risk in Communities Study cohort selected from four study centers in the United States by using a case-cohort design. The authors examined 137 incident cases of CHD and a stratified random sample of 2,252 examinees free of CHD at baseline. Baseline, supine, resting beat-to-beat heart rate data were collected. High- (0.16-0.35 Hz) and low- (0.025-0.15 Hz) frequency spectral powers and high-/low-frequency power ratio, estimated from spectral analysis, and standard deviation of all normal R-R intervals, calculated from time domain analysis, were used as the conventional indices of cardiac parasympathetic, sympatho-parasympathetic, and their balance, respectively. Incident CHD was defined as hospitalized myocardial infarction, fatal CHD, or cardiac revascularization procedures during 3 years of follow-up. The age, race, gender, and other CHD risk factor-adjusted relative risks (and 95% confidence intervals) of incident CHD comparing the lowest quartile with the upper three quartiles of high-frequency power, low-frequency power, high-/low-frequency power ratio, and standard deviation of R-R intervals were 1.72 (95% confidence interval (CI) 1.17-2.51), 1.09 (95% CI 0.72-1.64), 1.25 (95% CI 0.84-1.86), and 1.39 (95% CI 0.94-2.04), respectively. The findings from this population-based, prospective study suggest that altered cardiac autonomic activity, especially lower parasympathetic activity, is associated with the risk of developing CHD.

Case-Control Studies↗

Cardiac autonomic function during sleep and wakefulness in multiple sclerosis.

Some studies in multiple sclerosis (MS) patients have shown evidence of autonomic dysfunction involving the cardiovascular system. However, the findings in these studies have not been completely consistent. The discrepancy may be related to the limits of the traditional autonomic tests during wakefulness. In our study, after the investigation of the cardiovascular reflexes during wakefulness, heart rate (HR) variations were considered during sleep in order to avoid the limits of cooperation and the emotional state of the patient. We evaluated tonic (vagal activity) HR modifications in relation to the deepening of sleep, as well as phasic (sympathetic activity) HR modifications in relation to spontaneous body movements during sleep, in 25 MS patients and 25 age-matched controls. No difference was found between the two groups in autonomic function during wakefulness. A reduced parasympathetic activity was observed in MS subjects during both rapid eye movement (REM) and non-REM sleep, while no difference was found in sympathetic function between patients and controls. No significant correlation was found between cardiac autonomic data during sleep and MRI lesion load in the infratentorial areas and, in particular, of the brain stem. The findings of our study suggest that autonomic nervous system evaluation during sleep could show impairment earlier than the traditional autonomic tests during wakefulness.

Adult↗

Impaired cardiac autonomic functions in patients with environmental asbestos exposure: a study of time domain heart rate variability.

Environmental asbestos exposure is related to diffuse pleural disease (thickening and calcification) and restrictive pulmonary disease. To assess cardiac autonomic system, we investigated the time domain heart rate variability (HRV) by Holter monitoring and their correlation with pulmonary function tests in patients with pleural disease caused by environmental asbestos exposure. We studied 45 patients (26 men, 19 women, aged 62.67 +/- 10.1 years) and 35 healthy patients who had similar sex and age profile to the patients (24 men, 11 women, aged 59.31 +/- 8.4 years). The asbestosis group was divided into 3 subgroups according to the severity of forced vital capacity (FVC) severe (group 1) (n = 12): FVC less than 50% of expected, moderate (group 2) (n = 16): FVC 64%-51% of expected and mild (group 3) (n = 17): FVC 65%-80% of expected. HRV parameters were significantly different among all groups (P<.0001). Comparing the 4 groups (subgroups and control group), group 1 had the lowest mean HRV values and controls had the highest mean HRV values (P<.0001). Severity of autonomic dysfunction was correlated with the severity of FVC and arterial oxygen pressure. Right ventricular end-diastolic internal diameter (RVEDID) and right ventricular end-systolic internal diameter (RVESID) values were significantly increased in patients (P <.0001, P < 0.0001, respectively). Pulmonary acceleration time (AcT) values were shorter in all patient groups than control group (P <.0001). It was shortest in group 1. Group 2 and 3 had shorter AcT values than control group. HRV parameters were correlated positively with AcT values and negatively with RVEDID and RVESID values. In conclusion, patients with restrictive pulmonary disease due to environmental asbestos exposure had autonomic dysfunction, which was correlated with the severity of restriction. This was thought to be the result of chronic hypoxia, pulmonary hypertension, and right ventricular enlargement.

Analysis of Variance↗

Targeting neuronal nitric oxide synthase with gene transfer to modulate cardiac autonomic function.

Microdomains of neuronal nitric oxide synthase (nNOS) are spatially localised within both autonomic neurons innervating the heart and post-junctional myocytes. This review examines the use of gene transfer to investigate the role of nNOS in cardiac autonomic control. Furthermore, it explores techniques that may be used to improve upon gene delivery to the cardiac autonomic nervous system, potentially allowing more specific delivery of genes to the target neurons/myocytes. This may involve modification of the tropism of the adenoviral vector, or the use of alternative viral and non-viral gene delivery mechanisms to minimise potential immune responses in the host. Here we show that adenoviral vectors provide an efficient method of gene delivery to cardiac-neural tissue. Functionally, adenovirus-nNOS can increase cardiac vagal responsiveness by facilitating cholinergic neurotransmission and decrease beta-adrenergic excitability. Whether gene transfer remains the preferred strategy for targeting cardiac autonomic impairment will depend on site-specific promoters eliciting sustained gene expression that results in restoration of physiological function.

Adenoviridae↗

Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction.

The present study investigated the sympathetic/parasympathetic balance during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with psychogenic and organic erectile dysfunction. The cardiac autonomic balance was assessed from the power of the low frequency (LF) and high frequency (HF) spectral components of heart-rate variability in 11 patients with psychogenic erectile dysfunction and 11 patients with organic erectile dysfunction as determined by monitoring sleep-related erections. Spectral analysis of heart-rate variability was calculated for at least four successive 4-min epochs of electrocardiogram recordings during NREM sleep and for all available 4-min epochs during REM sleep. Statistical analysis revealed that organic patients had a significantly higher LF/HF ratio (P < 0.01) during both stages of sleep, which resulted from a significantly lower power in the HF component (P < 0.004) and higher power in the LF component (P < 0.01) in these patients, in both REM and NREM sleep stages. These results demonstrate that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep.

Adult↗

Heart rate variability analysis: a tool to assess cardiac autonomic function.

Heart rate monitoring is commonly used to provide an acute indicator of an individual's cardiovascular status and responsiveness. An increasingly popular technique involves quantifying the very small amounts by which the heart rate changes from one cardiac cycle to the next. This "heart rate variability (HRV) analysis" provides a substantial amount of additional information about the cardiovascular system and enables quantification of cardiac regulatory influences on the autonomic nervous system. The autonomic nervous system consists of two main components: the sympathetic system and the parasympathetic system. The relative influence of these two components on the sino-atrial node of the heart determines the heart rate. A number of physiological factors, including blood pressure and respiratory rate, can have a profound effect on this autonomic "balance." HRV analysis therefore provides a noninvasive method for investigating the dynamic influence of changing physiological parameters on cardiac regulation.

Autonomic Nervous System↗

Circadian change of cardiac autonomic function in correlation with intra-esophageal pH.

BACKGROUND AND AIM: Although autonomic alterations are observed in patients with gastroesophageal reflux disease (GERD), the influence of visceral receptor responses on the dynamics of autonomic function remains unknown. The aim of this study was to investigate the autonomic functional changes in association with intra-esophageal pH under ambulation. METHODS: Thirty patients referred for 48 h ambulatory pH monitoring underwent simultaneous 24 h cardiac monitoring for heart rate variability (HRV). We used linear mixed-effects models to estimate the relationship between esophageal acid exposure and power spectral analysis of HRV, including low-frequency power (0.04 < LF < 0.15 Hz), high-frequency power (0.15 < or = HF < 0.4 Hz), and LF/HF power ratio. RESULTS: Over the 24-h period, patients with pathological reflux had lower average LF and HF powers than patients with functional heartburn, but the LF/HF power ratios were similar for the two patient groups. As we stratified the data according to waking and sleeping times, a significantly higher HF power but lower LF/HF power ratio was found during sleeping time regardless of diagnosis. In the regression analysis, esophageal pH was positively associated with change (not basal tone) of both LF and HF powers during waking, but only with change of HF power during sleeping time. The significant associations between pH values and changes in HRV decreased gradually with time. The LF/HF power ratio did not alter significantly with pH. CONCLUSION: Esophageal acid exposure is generally associated with decreases in autonomic tone. A predominant parasympathetic fluctuation during sleeping and a superimposed sympathetic interaction during waking dictate diurnal characteristics of autonomic regulation.

Adult↗

[Effects of kidney and pancreas transplantation on neurophysiological rates of polyneuropathy and autonomous cardiac function in diabetic patients with end-stage renal disease].

BACKGROUND: Patients with type 1 diabetes mellitus (DM1) and end-stage renal disease (ESRD) usually exhibit a severe polyneuropathy (PNP) whose progression can be halted after kidney and pancreas transplantation (KPT). We studied the evolution of both PNP and autonomous cardioregulatory function (ACF) in patients with DM1 and ESRD within the first year after KPT. PATIENTS AND MEHTOD: The study was carried out in 26 patients who underwent KPT and whose organs were functioning normally at least during one year after KPT. They were examined neurophysiologically in three different periods: a) before KPT; b) 1-3 months after KPT, and c) 12 months after KPT. We evaluated PNP by measuring the conduction velocity (CV) and the amplitude of the compound action potentials (ACAP) of common peroneal, posterior tibial and sural nerves. ACF was evaluated by measuring the change in the interval separating two consecutive QRS complexes in the electrocardiogram during quiet breathing and Valsalva manoeuvre. RESULTS: All patients had a severe PNP before KPT. Ten patients (38.4%) showed a significant reduction in ACAP and ACF in the exam carried out within 1 to 3 months after KPT, whereas all patients showed an increase in the CV, ACAP and ACF at 1 year after KPT. CONCLUSIONS: KPT induces a significant improvement of neurophysiological signs of PNP and of ACF, which is statistically significant at 1 year after KPT. In some patients, the improvement is heralded by an increase in the axonal damage, occurring in the first months after KPT, which may be due the aggression from the surgical treatment and related events.

Adult↗

Continuous warm blood cardioplegia preserves cardiac autonomic function.

We studied in anesthetized dogs, the effects of cardiopulmonary bypass with normothermic whole blood, crossclamping of the aortic root, and continuous warm blood cardioplegia on the ability of the efferent sympathetic nervous system to augment the heart and that of the efferent parasympathetic nervous system to depress the heart. In control states, heart rate, atrial force of contraction, and right and left ventricular wall systolic pressures were augmented by stimulation of the intrathoracic efferent sympathetic nervous system and by administration of isoproterenol into the systemic circulation. After 1 hour of normothermic cardiopulmonary bypass that utilized aortic crossclamping and continuous perfusion of the coronary arteries with normothermic blood (20 mEq/L potassium), cardiac-augmenting effects induced by the efferent sympathetic nervous system and by isoproterenol were similar. Depressive responses elicited by the efferent parasympathetic nervous system were also unaffected by these procedures. Continuous warm blood cardioplegia does not result in impairment of the efferent sympathetic nervous system regulating the heart.

Animals↗

Power spectral analysis of heart rate variability: a noninvasive signature of cardiac autonomic function.

Power spectral analysis of short segments of beat-to-beat heart rate variability (PS/HRV) reveals three distinct peaks. In human PS/HRV, the high frequency (HF) band (0.15 to 0.4 Hz) is correlated with respiratory driven vagal efferent input to the sinus node. The low frequency band (LF) 0.06 to 0.15 Hz is believed to be due to baroreceptor mediated blood pressure control. Therefore, PS/HRV represents a noninvasive signature of the balance between sympathetic and parasympathetic components of the autonomic nervous system. This paper reviews the literature on the methodological issues relevant to signal processing, computational, and clinical applications of PS/HRV. Factors affecting the power in the LF and HF bands are examined in healthy controls. Recent work from several laboratories suggests that PS/HRV is a potentially powerful tool for exploring neurocardiac dysfunction in patients with a variety of cardiac and autonomic disorders. Mathematical models which simulate neurocardiac control are examined. Concerns regarding the lack of standardization between different laboratories are expressed. As the PS/HRV attains the status of a clinical diagnostic test, we hope that this review serves as a source of integrated information for researchers in this field.

Adult↗

Spectral indices of cardiac autonomic function in obstructive sleep apnea.

Spectral analysis of heart rate variability (HRV) is useful as a noninvasive means of assessing autonomic function in patients with obstructive sleep apnea (OSA). However, standard spectral measures, such as the ratio of low-frequency to high-frequency power (LHR) and normalized high-frequency power (NHFP), can be confounded by the abnormal breathing patterns that occur during sleep. To circumvent this limitation, we employed an autoregressive modeling approach to partition the RR time-series into a component that is correlated with respiration and a respiration-independent component. From these components, we derived two new spectral indices: the modified LHR (MLHR) and the average gain relating respiration to RR changes (GRSA). Six normals and seven OSA patients were studied in relaxed wakefulness and stage 2 sleep; during sleep, the OSA patients were studied without and with continuous positive airway pressure (CPAP) therapy. All four spectral indices showed significant differences between OSA patients and normals in both wakefulness and sleep, although the changes in MLHR and GRSA were substantially larger and less variable: MLHR (p < 0.0003) and GRSA (p < 0.0001) vs. LHR (p < 0.005) and NHFP (p < 0.004). However, in the OSA subjects, LHR and NHFP were unchanged by CPAP. By contrast, CPAP produced a highly significant increase in GRSA (p < 0.0004), as well as a decrease in MLHR (p < 0.03). Thus, by compensating for the effects of breathing pattern differences, MLHR and GRSA unmasked the effects of CPAP therapy, which has been shown in previous studies to reduce sympathetic activity and increase vagal cardiac modulation.

Adult↗