Mario J. Carvalho

Diurnal Blood Pressure Variation in Progressive Autonomic Failure

To investigate the role of the autonomic nervous system (ANS) in the generation of the circadian blood pressure (BP) variation, the degree of impairment of the ANS was related to the results of ambulatory BP recordings in 212 patients with progressive autonomic failure due to familial amyloid polyneuropathy. On the basis of BP and/or heart rate (HR) responses to the Valsalva maneuver, 60 degrees head-up tilting, deep-breathing tests, and plasma norepinephrine levels, 4 groups of patients were distinguished. In all patients and in 38 age-matched control subjects, ambulatory BP was monitored. Patients of group I (n=40, aged 32+/-3 y), with no evidence yet of impairment of their ANS, had circadian BP and HR variations indistinguishable from controls. Patients of group II (n=41, aged 34+/-5 y) had a variable degree of impairment of their parasympathetic ANS, but their sympathetic ANS was still intact. Twenty-four-hour HR was higher in these patients than in controls (88+/-11 versus 78+/-7 bpm, P<0.01). Their circadian HR variation was maintained, but their circadian BP variation was diminished (10+/-6/11+/-4 versus 17+/-6/16+/-4 mm Hg in controls, P<0.01) because of an attenuation of the nocturnal BP decline. Patients of group III (n=69, aged 36+/-6 y), with parasympathetic failure and intermediate sympathetic dysfunction, had a blunted diurnal BP variation, whereas patients of group IV (n=62, aged 38+/-6 y), with parasympathetic failure and severe sympathetic dysfunction, had an absent diurnal BP variation. In patients of groups III and IV, a decrease in daytime BP accounted for the blunted circadian BP variation. This extensive study in progressive autonomic failure confirms the important role of the ANS in the generation of circadian BP variation. For the maintenance of a normal circadian BP pattern, not only an intact sympathetic but also an intact afferent parasympathetic ANS is a prerequisite.

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol β-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and α index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.

Circadian heart rate variability rhythm in shift workers

The objective of this study was to assess the influence of day-night cycle and sleep-awake period on the circadian pattern of heart rate variability (HRV). Twelve male oil refinery security shift workers, aged 39 +/- 7 years, were studied with 24-hour Holter monitor recordings during morning and night work periods. Hourly HRV parameters in the time and frequency domains were evaluated. For both shifts, all HRV parameters during awake or work periods were found not to be statistically different. In both day and night work shifts, the very low frequency and high-frequency components of HRV and the proportion of differences in successive R-R intervals greater than 50 ms increased during the sleep period, while the low frequency/high frequency ratio decreased. The low-frequency component in absolute units and the SD of the R-R interval did not show any variation in either shifts for the different periods. These results suggest that the circadian pattern of HRV seems to be predominantly related to sleep (supine) and wakefulness (standing) and remains independent of night-day cycle.

Role of Sympathetic Nervous System in Cyclosporine-Induced Rise in Blood Pressure

To clarify the role of the sympathetic nervous system in the development of cyclosporine A (CsA)-induced rise in blood pressure (BP), the effects of CsA on 24-hour ambulatory BP (ABP) were studied in patients with familial amyloid polyneuropathy (FAP) who underwent a liver transplantation. On the basis of autonomic function tests, patients with absent or mild-to-moderate sympathetic damage (Group A, n=11, age 29 to 43 years, disease duration 2 to 6 years) and patients with severe sympathetic damage (Group B, n=9, age 27 to 38 years, disease duration 3 to 9 years) were identified. Both groups were followed for 1 year. The daily doses of CsA and the CsA whole blood trough levels between the groups did not differ. Pretransplantation values of daytime and nighttime ABP were, respectively, 117+/-8/76+/-7 mm Hg and 108+/-12/68+/-9 mm Hg in group A and 107+/-6/66+/-4 mm Hg (P<0.05 group A versus group B) and 102+/-6/62+/-4 mm Hg in group B. In response to CsA, BP increased in all patients, but more so in patients of group B than in patients of group A. One year after transplantation, daytime and nighttime ABP had increased by 6+/-9/3+/-11% and 12+/-10/14+/-14% in group A and by 12+/-6/13+/-10% (P<0.05) and 21+/-11/27+/-21% (P<0.01) in group B. In both groups, the increase in nighttime ABP was greater than the increase in daytime ABP, which resulted in an attenuation or, even, a reversal of the diurnal BP rhythm. Because the rise in BP was greater in patients with more advanced sympathetic dysfunction, the sympathetic nervous system appears to counteract the CsA-induced rise in BP rather than causing it. This implies involvement of factors other than sympathetic activation in the pathogenesis of CsA-induced rise in BP in patients with familial amyloid polyneuropathy.

Heart rate variability in 24-hour holter recordings: Comparative study between short- and long-term time- and frequency-domain analyses

Mean hourly parameters obtained from all beats (long series) were compared with those obtained from a sample of 512 beats extracted each hour (short series) in nine presumably normal subjects. For both the short and long series, the spectral components, very low frequency, (VLF), low frequency (LF), and high frequency (HF), and time-domain indices (such as the Ewing statistic [PNN50] and RR standard deviation [SD-RR]), have been estimated. The spectral components LF and HF, estimated from the short and long series, were not significantly different, whereas significant differences were found between VLF, SD--RR, and PNN50. In both the short and long series, a strong correlation was found between LF and SD-RR and between HF and PNN50. The results suggest that, over a period of 24 hours, hourly LF and HF spectral components can be obtained using a single series of 512 beats every hour, with a great advantage over the evaluation of the mean hourly parameters. This method would be particularly useful in the study of circadian heart rate spectral analysis in Holter recordings with multiple artifacts or ectopic beats, and in general, when analysis of the entire 24-hour series is not feasible.

High altitude-related neurocardiogenic syncope

This report presents a well-documented link between vasodepressor syncope, a marked increase of LF/HF ratio response to orthostasis (sympathetic dominance), and the efficacy of beta blockers in preventing orthostatic symptoms and absence of tilt-induced syncope, with normalization of the LF/HF ratio response.

Spectral Analysis of R-R Variability in Familial Amyloidotic Polyneuropaty, Andrade Type

Spectral analysis of R-R variability has been done in twenty subjects with Familial Amyloidotic Polyneuropathy in order to define intensity, chronology and discriminative capacity of this method in parasympathetic and sympathetic disturbances. The subjects were subdivided in 3 groups. Group I with far advanced disease, group II in early stages of the disease and group III with asymptomatic carriers. The R-R spectral analysis was calculated after fast Fourier transform in supine and after 60 tilt. Valsalva manoeuvre, deep breathing and standing were performed in groups II and III. The results showed a very severe autonomic disturbance in group I.The parasympathetic system seems to be early affected even in some asymptomatic carriers. Heart rate spectral analysis seems to be more sensitive for detection of autonomic disturbances than other autonomic tests.