Ivabradine: Just another New Pharmacological Option for Heart Rate Control?

Ivabradine (IVB) is a heart rate lowering agent that acts via selective inhibition of the pacemaker funny current in sinoatrial nodal P cells, thus, reducing heart rate at rest and during exercise with minimal effect on myocardial contractility, blood pressure, and intracardiac conduction. IVB exerts no effect on external respiratory function parameters and it may also play a role in patients with concurrent chronic obstructive pulmonary disease. This property constitutes an important advantage over β-blockers. IVB acts by reducing the heart rate in a mechanism different from β-blockers, calcium channel blockers or late sodium channel blockers, three commonly prescribed antianginal drugs. As clinical trials have shown, it is remarkably well-tolerated and offers an alternative for patients who cannot take β-blockers. The combination of IVB and atenolol at commonly used doses in patients with chronic stable angina produced additional efficacy with no untoward effect on safety or tolerability. Additionally, side effects are rare and largely limited to a luminous phenomenon or phosphenes. This sensation is thought to be due to a block of Ih in the retina, a current very similar to cardiac If channels. IVB is contraindicated in patients with sick sinus syndrome or sinus node dysfunction and in patients taking hepatic inhibitors of Cytochrome P450 family 3, subfamily A, polypeptide 4 (abbreviated CYP3A4), with exception of omeprazole or lansoprazole. This review briefly summarizes the main studies regarding this drug.

Fractal scaling exponents of heart rate variability association with linear indices and Poincaré Plot

The literature indicated that the fractal analysis of heart rate variability (HRV) is related to the chaos theory. However, it is not clear if the both short and long-term fractal scaling exponents of HRV are reliable for short period analysis in women. We evaluated the association of the fractal exponents of HRV with the time and frequency domain and geometric indices of HRV. We evaluated 65 healthy women between 18 and 30 years old. HRV was analyzed with a minimal number of 256 RR intervals in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains, the geometric index were also analyzed (triangular indexRRtri, triangular interpolation of RR intervals-TINN and Poincaré plot-SD1, SD2 and SD1/SD2) as well as short and long-term fractal exponents (alpha-1 and alpha-2) of the detrended fluctuation analysis (DFA). No significant correlation was observed for alpha-2 exponent with all indices. There was significant correlation of the alpha-1 exponent with RMSSD, pNN50, SDNN/RMSSD, LF (nu), HF (nu and ms2 ), LF/HF ratio, SD1 and SD1/SD2 ratio. Our data does not indicate the alpha-2 exponent to be used for 256 RR intervals and we support the alpha-1 exponent to be used for HRV analysis in this condition.

Fractal dynamics of heart rate variability for short term

The fractal analysis of heart rate variability (HRV) has been associated to the chaos theory. We evaluated the association of the fractal exponents of HRV with the time and frequency domain and geometric indices of HRV for short period. HRV was analyzed with a minimal number of 256 RR intervals in the time (SDNN-standard deviation of normal-to-normal R-R intervals, pNN50-percentage of adjacent RR intervals with a difference of duration greater than 50ms and RMSSD-root-mean square of differences between adjacent normal RR intervals in a time interval) and frequency (LF-low frequency, HF-high frequency and LF/HF ratio) domains. The geometric indexes were also analyzed (RRtri-triangular index, TINN-triangular interpolation of RR intervals and Poincaré plot) as well as short and long-term fractal exponents (alpha-1 and alpha-2) of the detrended fluctuation analysis (DFA). We observed strong correlation of the alpha-1 exponent with RMSSD, pNN50, SDNN/RMSSD, LF (nu), HF (nu), LF/HF ratio, SD1 and SD1/Sd2 ratio. In conclusion, we suggest that the alpha-1 exponent could be applied for HRV analysis with a minimal number of 256 RR intervals.

Fractal correlation property of heart rate variability in response to the postural change maneuver in healthy women

Background: We evaluated the effects of the PCM on the fractal analysis of the HRV in healthy women Method: We evaluated healthy women between 18 and 30 years old. HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains as well as short and long-term fractal exponents (alpha-1 and alpha-2) of the detrended fluctuation analysis (DFA). HRV was recorded at rest for ten minutes at seated rest and then the women quickly stood up from a seated position in up to three seconds and remained standing for 15 minutes. HRV was recorded at the following time: rest, 0–5 min, 5–10 min and 10–15 min during standing. Results: We observed decrease (p < 0.05) in the time-domain indices of HRV between seated and 10–15 minutes after the volunteer stood up. The LF (ms2) and HF (ms2) indices were also reduced (p < 0.05) at 10–15 minutes after the volunteer stood up compared to seated while the LF (nu) was increased at 5–10 min and 10–15 min (p < 0.05). The short-term alpha-1 exponent was increased (p < 0.05) at all moments investigated compared to seated. Increase in the properties of short-term fractal correlations of heart rate dynamics accompanied by a decrease in the parasympathetic modulation and global HRV was observed in response to the postural change maneuver. Conclusion: We suggest that fractal analysis of HRV is more sensitive than frequency and time-domain analysis of HRV during the postural change maneuver.

Chronic obstructive pulmonary disease and heart rate variability: a literature update

Background: The literature indicates that chronic obstructive pulmonary disease (COPD) affects cardiac autonomic control. In this study, we conducted a literature review in order to investigate the heart rate variability (HRV) in COPD subjects. Methods: A search was performed in Medline database, using the link between the keywords: “autonomic nervous system”, “cardiovascular system”, “COPD” and “heart rate variability”. Results: The search resulted in a total of 40 references. Amongst these references, the first exclusion resulted in the barring of 29 titles and abstracts, which were not clearly related to the purpose of review. This resulted in a total of 11 articles that were then read and utilized in the review. The selected studies indicated that there is significant reduction of HRV in patients with COPD, characterized by reduction of indices that assess parasympathetic activity in addition to dealing with the global autonomic modulation. We also established that supervised exercise can reduce these harmful effects in COPD patients. Also, it was reported that the use of non-invasive ventilation in these patients may contribute to the improvement of respiratory symptoms, with no impairing, and may even induce positive responses in cardiac autonomic regulation. Conclusion: The studies indicate a need for further investigations to guide future therapies to improve the treatment of cardiovascular system in the respiratory diseases.

Auditory stimulation with music influences the geometric indices of heart rate variability in men

Background: Chronic classical music was reported to increase parasympathetic activitywhen evaluating heart rate variability (HRV). It is poor in the literature investigation of the acute effects of baroque and heavy metal styles of musical auditory stimulation on HRV. In this study we evaluated the acute effects of relaxant baroque and excitatory heavy metal music on the geometric indices of HRV in healthy men. Method: The study was performed in 12 healthy men between 18 and 30 years old. We excluded persons with previous experience with music instrument and those who had affinity with the song styles. We analyzed the following indices: RRtri, TINN and Poincaré plot (SD1, SD2 and SD1/SD2 ratio). HRV was recorded at rest for ten minutes. Subsequently they were exposed to relaxant baroque or excitatory heavy metal music for five minutes through an earphone. After the first music exposure they remained at rest for more five minutes and them they were exposed again to Baroque or Heavy Metal music (65–80 dB). The sequence of songs was randomized for each individual. Results: The RRTri and SD2 indices were reduced during the heavy metal musical auditory stimulation (p < 0.05). No changes were observed regarding TINN, SD1 and SD1/SD2 ratio (p > 0.05).The qualitative Poincaré plot analysis indicated that during relaxant classical baroque music there was observed a higher beat-to-beat dispersion of RR intervals compared with no music exposure and during excitatory heavy metal musical auditory stimulation, showing higher HRV. Conclusion: We suggest that excitatory heavy metal music acutely decreases global HRV.

An exploration of heart rate response to differing music rhythm and tempos

The aim of this study was to investigate acute cardiac response and heart rate variability (HRV) when listening to differing forms of music. Eleven healthy men aged between 18 and 25 years old were included in the study. HRV was recorded at rest for ten minutes with no music, then were asked to listen to classical baroque or heavy metal music for a period of 20 min. It was noted that heart rate variability did not affect HRV indices for time and frequency. In conclusion, music with different tempos does not influence cardiac autonomic regulation in men. However more studies are suggested to explore this topic in greater detail.

Autonomic control of heart rate during orthostasis and the importance of orthostatic-tachycardia in the snake Python molurus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Temperature effects on baroreflex control of heart rate in the toad, Rhinella schneideri

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute effects of flexible pole exercise on heart rate dynamics

Introduction: Exercise with flexible poles provides fast eccentric and concentric muscle contractions. Although the literature reports significant muscle chain activity during this exercise, it is not clear if a single bout of exercise induces cardiac changes. In this study we assessed the acute effects of flexible pole exercise on cardiac autonomic regulation.Methods: The study was performed on 22 women between 18 and 26 years old. We assessed heart rate variability (HRV) in the time (SDNN, RMSSD and pNN50) and frequency (HF, LF and LF/HF ratio) domains and geometric indices of HRV (RRTri, TINN, SD1, SD2 and SD1/SD2 ratio). The subjects remained at rest for 10 min and then performed the exercises with the flexible poles. Immediately after the exercise protocol, the volunteers remained seated at rest for 60 min and HRV was analyzed.Results: We observed no significant changes in time domain (SDNN: p=0.72; RMSSD: p=0.94 and pNN50: p=0.92) or frequency domain indices (LF [nu]: p=0.98; LF [ms(2)]: p=0.72; HF [nu]: p=0.98; HF [ms(2)]: p=0.82 and LF/HF ratio: p=0.7) or in geometric indices (RRTri: p=0.54; TINN: p=0.77; SD1 p=0.94; SD2: p=0.67 and SD/SD2: p=0.42) before and after a single bout of flexible pole exercise.Conclusion: A single bout of flexible pole exercise did not induce significant changes in cardiac autonomic regulation in healthy women. (C) 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Can geometric indices of heart rate variability predict improvement in autonomic modulation after resistance training in chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is associated with autonomic dysfunctions that can be evaluated through heart rate variability (HRV). Resistance training promotes improvement in autonomic modulation; however, studies that evaluate this scenario using geometric indices, which include nonlinear evaluation, thus providing more accurate information for physiological interpretation of HRV, are unknown. This study aimed to investigate the influence of resistance training on autonomic modulation, using geometric indices of HRV, and peripheral muscle strength in individuals with COPD. Fourteen volunteers with COPD were submitted to resistance training consisting of 24 sessions lasting 60 min each, with a frequency of three times a week. The intensity was determined as 60% of one maximum repetition and was progressively increased until 80% for the upper and lower limbs. The HRV and dynamometry were performed at two moments, the beginning and the end of the experimental protocol. Significant increases were observed in the RRtri (4·81 ± 1·60 versus 6·55 ± 2·69, P = 0·033), TINN (65·36 ± 35·49 versus 101·07 ± 63·34, P = 0·028), SD1 (7·48 ± 3·17 versus 11·04 ± 6·45, P = 0·038) and SD2 (22·30 ± 8·56 versus 32·92 ± 18·78, P = 0·022) indices after the resistance training. Visual analysis of the Poincare plot demonstrated greater dispersion beat-to-beat and in the long-term interval between consecutive heart beats. Regarding muscle strength, there was a significant increase in the shoulder abduction and knee flexion. In conclusion, geometric indices of HRV can predict improvement in autonomic modulation after resistance training in individuals with COPD; improvement in peripheral muscle strength in patients with COPD was also observed.

Impact of obesity on autonomic modulation, heart rate and blood pressure in obese young people

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)