Valdo José Dias da Silva

Effects of Long-Term Exercise Training on Autonomic Control in Myocardial Infarction Patients

Autonomic dysfunction, including baroreceptor attenuation and sympathetic activation, has been reported in patients with myocardial infarction (MI) and has been associated with increased mortality. We tested the hypotheses that exercise training (ET) in post-MI patients would normalize arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA), and long-term ET would maintain the benefits in BRS and MSNA. Twenty-eight patients after 1 month of uncomplicated MI were randomly assigned to 2 groups, ET (MI-ET) and untrained. A normal control group was also studied. ET consisted of three 60-minute exercise sessions per week for 6 months. We evaluated MSNA (microneurography), blood pressure (automatic oscillometric method), heart rate (ECG), and spectral analysis of RR interval, systolic arterial pressure (SAP), and MSNA. Baroreflex gain of SAP-RR interval and SAP-MSNA were calculated using the &agr;-index. At 3 to 5 days and 1 month after MI, MSNA and low-frequency SAP were significantly higher and BRS significantly lower in MI patients when compared with the normal control group. ET significantly decreased MSNA (bursts per 100 heartbeats) and the low-frequency component of SAP and significantly increased the low-frequency component of MSNA and BRS of the RR interval and MSNA. These changes were so marked that the differences between patients with MI and the normal control group were no longer observed after ET. MSNA and BRS in the MI-untrained group did not change from baseline over the same time period. ET normalizes BRS, low-frequency SAP, and MSNA in patients with MI. These improvements in autonomic control are maintained by long-term ET. These findings highlight the clinical importance of this nonpharmacological therapy based on ET in the long-term treatment of patients with MI.

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23+/-0.1 vs. 1.32+/-0.2 ms2) and HF (6.6+/-0.49 vs. 15.1+/-0.61 ms2) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3+/-2.7 vs. 7.4+/-1.01 mmHg2) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (-1.83+/-0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23+/-0.06 bpm/mmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels.

Effects of Spinal Section and of Positive-Feedback Excitatory Reflex on Sympathetic and Heart Rate Variability

The sympathetic outflow appears to be capable of displaying a rhythmicity synchronous with cardiovascular Mayer’s waves even after spinal section. To test the hypothesis that spinal sympathetic low frequency (LF) oscillation can be enhanced during sympathetic excitation, we recorded cardiac sympathetic nerve activity (SNA), R-R interval, arterial pressure, and ventilation in 9 unanesthetized decerebrate-vagotomized cats before and after C1 spinal section. LF and high frequency (HF) components were detected in the variability of SNA, R-R interval, and systolic arterial pressure both before and after spinal section. In this latter condition, a significant coherence between LFSNA and LFR-R was present in 5 animals, whereas HFSNA and HFR-R were correlated in 4 animals. During an excitatory sympathetic spinal reflex elicited by aortic constriction, the efferent sympathetic firing was markedly enhanced (from 7±2 to 33±7 spikes/s); concomitantly, the powers of both LFSNA and HFSNA were also increased. Coherence between LFSNA and LFR-R became significant in all cases, whereas HFSNA and HFR-R became correlated in 6 animals. In 3 animals, the reflex sympathetic excitation was no longer elicitable after interrupting a vast contingent of sympathetic afferents by means of thoracic dorsal root section. We report for the first time that LF and HF oscillations are detectable in SNA, R-R interval, and systolic arterial pressure variabilities of decerebrate-vagotomized spinal cats and that an excitatory spinal reflex is capable of increasing the power of both SNA spectral components.

Power Spectral Analysis of Heart Rate Variability in HIV‐Infected and AIDS Patients

Background: In HIV‐infected patients the risks for cardiovascular disease are multifactorial. Autonomic dysfunction has been detected in the early phase of HIV infection as well as in AIDS patients with advanced cardiomyopathy.

Arterial Baroreceptors and Experimental Diabetes

Abstract: Alterations of the autonomic reflex control of the cardiovascular system have been demonstrated in clinical and animal models of insulin‐dependent diabetes mellitus. Established neuroaxonal dystrophy is considered the neuropathological hallmark of chronic experimental diabetes. However, the afferent arm of the arterial baroreflex, that is, the carotid sinus nerve and the aortic depressor nerve, has received much less attention in studies dealing with this physiopathological model. The attenuation of the pressure response to bilateral carotid occlusion in conscious rats indicates a derangement of the baroreflex, probably involving an alteration of the carotid sinus nerve. There is histological evidence obtained from adult spontaneous insulin‐dependent diabetic rats (strain BB/S) of a carotid sinus nerve with signs of axonal swelling and intramyelinic edema, suggesting diabetic neuropathy. The study of aortic baroreceptor activity in anesthetized rats with short‐ and long‐term streptozotocin diabetes by means of cross‐spectral analysis of baroreceptor activity versus arterial pressure revealed a dysfunction in the afferent arm of the baroreflex even during a short period of diabetes. The morphology of the aortic depressor nerve of streptozotocin‐diabetic rats indicated axonal atrophy by visual analysis remarkably at the distal segments of the nerves. This finding was confirmed by morphometric study of the myelinated fibers. In conclusion, although studies of the arterial baroreceptors related to experimental diabetes are scanty in the literature, there is electrophysiological and histological evidence demonstrating that the carotid sinus and the aortic depressor nerves are abnormal in this experimental model.

Sympathetic rhythms and cardiovascular oscillations

Spectral analysis of heart rate and arterial pressure variabilities is a powerful noninvasive tool, which is increasingly used to infer alterations of cardiovascular autonomic regulation in a variety of physiological and pathophysiological conditions, such as hypertension, myocardial infarction and congestive heart failure. A most important methodological issue to properly interpret the results obtained by the spectral analysis of cardiovascular variability signals is represented by the attribution of neurophysiological correlates to these spectral components. In this regard, recent applications of spectral techniques to the evaluation of the oscillatory properties of sympathetic efferent activity in animals, as well as in humans, offer a new approach to a better understanding of the relationship between cardiovascular oscillations and autonomic regulation.

Sildenafil acts on the central nervous system increasing sympathetic activity

Sildenafil induces vasodilation and is used for treating erectile dysfunction. Although its influence on resting heart function appears to be minimal, recent studies suggest that sildenafil can increase sympathetic activity. We therefore tested whether sildenafil injected into the central nervous system alters the autonomic control of the cardiovascular system in conscious rats. The effect of sildenafil citrate injected into the lateral cerebral ventricle was evaluated in conscious rats by means of the recording of lumbar sympathetic nerve activity (LSNA), spectral analysis of systolic arterial pressure and heart rate variability, spontaneous baroreflex sensitivity, and baroreflex control of LSNA. Intracerebroventricular (ICV, 100 microg /5 microl) administration of sildenafil caused remarkable tachycardia without significant change in basal arterial pressure and was associated with a conspicuous increase (47 +/- 14%) in LSNA. Spectral analysis demonstrated that systolic arterial pressure oscillations in the low frequency (LF) range were increased (from 6.3 +/- 1.5 to 12.8 +/- 3.8 mmHg(2)), whereas the high frequency (HF) range was not affected by ICV administration of sildenafil. Sildenafil increased pulse interval oscillations at LF and decreased them at HF. The LF-HF ratio increased from 0.04 +/- 0.01 to 0.17 +/- 0.06. Spontaneous baroreflex sensitivity measured by the sequence method and the baroreflex relationship between mean arterial pressure and LSNA were not affected by ICV administration of sildenafil. In conclusion, sildenafil elicited an increase in sympathetic nerve activity that is not baroreflex mediated, suggesting that this drug is able to elicit an autonomic imbalance of central origin. This finding may have implications for understanding the cardiovascular outcomes associated with the clinical use of this drug.

Intravenous amiodarone modifies autonomic balance and increases baroreflex sensitivity in conscious rats

Amiodarone is an antiarrhythmic agent commonly used to treat cardiac arrhythmias. This study was designed to investigate the effects of intravenous amiodarone on the neural control of heart rate and arterial pressure and spontaneous baroreflex sensitivity (BRS). Experiments were carried out on conscious freely moving normotensive Wistar (WR) and spontaneously hypertensive rats (SHR). Arterial pressure was continuously monitored before and after amiodarone (50 mg/kg i.v.) or vehicle for 30 min. Heart rate (expressed as the pulse interval, PI) and systolic arterial pressure (SAP) variabilities were assessed using autoregressive spectral analysis. BRS was calculated as the alpha-index (the square root of the ratio between the PI and SAP powers). Amiodarone induced bradycardia and hypotension in both strains, with these effects being more intense in SHR. The variability profile of PI was characterized by a significant reduction of normalized low frequency (LF) and LF/HF ratio, while the high frequency (HF) component both in absolute and normalized units (nu) was increased in both WR and SHR strains. A significant decrease in SAP variance and its LF oscillation was observed. In addition, BRS was also increased in both groups, being more intense in SHR. In both WR and SHR, intravenous amiodarone had a considerable effect on heart rate variabilities (HRV), shifting cardiac sympathovagal balance toward a sympathetic inhibition and/or vagal activation, which were associated with an increase in spontaneous BRS. Decreases of SAP variance and LF(SAP) suggest sympatholytic effects on peripheral vessels. Besides the direct ion channel effects, these changes in the autonomic balance could contribute to the antiarrhythmic action of the intravenous amiodarone.

Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinsons disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development.

Time delay of baroreflex control and oscillatory pattern of sympathetic activity in patients with metabolic syndrome and obstructive sleep apnea.

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS - OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS - OSA (P < 0.01) and C (P < 0.001). The sensitivity of the ABRMSNA was lower and the time delay was greater in MetS + OSA compared with MetS - OSA (P < 0.001 and P < 0.01, respectively) and C (P < 0.001 and P < 0.001, respectively). Patients with MetS - OSA showed decreased oscillatory pattern of MSNA compared with C (P < 0.01). The sensitivity of the ABRMSNA was lower in MetS - OSA than in C group (P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.