Test with external peripheral vascular occlusion in evaluation of ergoreflex in patients with chronic obstructive pulmonary disease

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COPD presents a worldwide problem nowadays. To WHO estimates, the disease is the third cause of mortality and disability [1-3]. The main symptoms of COPD are dyspnea on exercise, reduction of tolerance to exercise and cough acquiring chronic character [2, 4].

Besides, an important characteristics of COPD is manifestation of systemic effects. Hypoxemia, smoking, reduction of physical activity and other factors form the basis for systemic inflammation, cachexia and dysfunction of skeletal muscles. Barreiro, et al. in their research (2016) emphasize the importance of routine evaluation of dysfunction of muscles in COPD as a common systemic manifestation [5]. Due to the above, patients with COPD restrict the level of physical activity, suffer from impairment of the quality of life. For evaluation of the functional condition of patients with COPD, heart rate variability (HRV) is used [6]. Method of examination of HRV permits to evaluate functioning of regulatory systems of an organism, of the activity of sympathetic and parasympathetic divisions of the autonomic nervous system (ANS) [7].

In the literature, a relationship is seen between severity of bronchial obstruction and HRV parameters in patients with bronchial asthma and COPD [8, 9] which may be used for complex evaluation of the functional condition of patients.

In the context of a significant role of systemic effects of COPD, the priority task  is to study functional disorders of skeletal muscles in patients with COPD and the reflex from receptors of muscle tissue of the lower limbs (ergoreflex) which is understood as a reflex regulation of an organism in response to mechanical stretch and accumulation of metabolites in muscles [10]. Ergoreflex may be a connective link between the autonomic imbalance, the level of tolerance to  physical load and the functional status of patients with COPD.

The aim of study is to evaluate changes in the cardiointervalogram (CIG) in the test with external peripheral vascular occlusion in patients with COPD and in individuals without diseases of the respiratory system.

Materials and Methods

The study involved 64 patients with COPD (age 64.98±8.67 years) and 41 volunteers with no diseases of the respiratory system (age 61.68±9.21 years, p>0.05). Participants were also statistically comparable in gender – only men were included.

The study was approved at a meeting №3 (09.11.2016) of Local ethical committee of Ryazan State Medical University. All participants signed Informed consent. 

The study included record of CIG three times: before the test, during the test with external peripheral vascular occlusion, and after the test. HRV was evaluated by R.M. Baevsky method [11], with use of Varicard hardware-software complex (OOO Ramena, Russia). The participants were offered to lie on the back, breathe through the nose, not to perform unnecessary movements and not to talk. For the test with occlusion, cuffs were used inflated with air and preliminarily applied on the hips of lower limbs. The activity of ergoreflex was evaluated by evidence of changes in CIG.

The results were statistically processed using application program package Excel 2010 (Microsoft Corporation, USA) and Statistica 13.0 (Stat Soft Inc., USA). Correspondence of variable to normal distribution was determined using Kolmogorov-Smirnov and Shapiro-Wilk tests. Quantitative data satisfying normal distribution are presented as mean value (M) ± standard deviation (σ). Data not satisfying normal distribution were presented as median and interquartile range: Me [Q25-Q75].

For comparison of mean values in complexes with normal distribution of a characteristic in groups, Student’s t-test was used, in case of absence of characteristics of normal distribution of data, Mann-Whitney U-test was used. For comparison of parameters of dependent groups with normal distribution of a characteristic in groups, paired Student’s t-test was used, with distribution different from normal – Wilcoxon paired criteria. The values were considered statistically significant at р<0.05.

Results and Discussion

Analysis of clinical characteristics of patients with COPD and of respondents of the control group did not show statistically significant differences in the following parameters: BMI – 27.5 [23.9;30.6] and 28.4 [26.5;29.7] kg/m²; heart rate (HR) – 72.8±11.0 and 69.8±8.9 beat/min: respiratory rate (RR) – 15.6±4.4 and 14.8±4.3/min; index of the activity of regulatory systems (IARS) – 5.0 [4.0;6.0] and 4.0 [4.0;6.0] conv. un.; mean duration of RR interval (Mean) – 842.6±125.1 and 873.4±113.4 msec; the most common duration of RR intervals (Mo) – 838.9±117.0 and 873.7±116.6 msec, respectively (for all comparisons p>0.05). For other analyzed parameters statistically significant differences were obtained (p<0.05, Table 1).

 

Table 1 Comparative Analysis of Initial Parameters of Heart Rate Variability in Patients with COPD and Volunteers with no Respiratory Diseases

Parameter	Patients with COPD	Volunteers  with no Respiratory Diseases	p
n	64	41	–
HR, beat./min	72.8±11.0	69.8±8.9	0.15
RR per min	15.6±4.4	14.8±4.3	0.39
IARS	5.0 [4.0;6.0]	4.0 [4.0;6.0]	0.22
RMSSD, msec	25.0 [13.0;66.0]	14.0 [10.0;25.0]	0.001
SDNN, msec	30.0 [19.0;55.0]	23.0 [17.0;31.0]	0.028
CV, %	3.5 [2.3;5.7]	2.6 [2.0;3.6]	0.007
Mean, msec	842.6±125.1	873.4±113.4	0.20
Mo, msec	838.9±117.0	873.7±116.6	0.14
TP, msec2	595.1 [226.5;1796.9]	344.4 [185.8;825.2]	0.047
PHF, %	46.3 [29.0;66.5]	29.7 [14.5;46.4]	0.0003
PLF, %	27.7 [16.8;39.7]	34.4 [25.3;42.3]	0.044
PVLF, %	20.0 [7.8;31.0]	27.9 [19.8;47.6]	0.001
LF/HF	0.6 [0.3;1.2]	1.4 [0.6;2.8]	0.0004
IC	1.2 [0.5;2.5]	2.4 [1.2;5.9]	0.0003

Note: RMSSD – root-mean-square difference between duration of neighboring RR intervals; SDNN – standard deviation of  NN intervals, reflects the total effect of autonomic regulation of heart rhythm; CV – coefficient of  variation; TP – total power of spectrum; PHF – relative power of high-frequency oscillations; PLF – relative power of low-frequency oscillations;  PVLF – relative power of ‘very’ low-frequency oscillations; LF/HF – proportion between sympathetic and parasympathetic influence on the heart rhythm; IC – index of centralization

 

The activity of ergoreflex was evaluated by comparison of CIG parameters in three stages of the research: initial HRV, during test with occlusion and immediately on completion of the test. The results of research for patients with COPD are given in Table 2.

 

Table 2 Comparative Analysis of Parameters of Heart Rhythm Variability  in Evaluation of Ergoreflex in Patients with COPD

Parameter	Patients with COPD (n=64)
	Initially	In the test	After the test
HR, beat/min	72.8±11.0*	72.6±10.8**	71.6±10.5
RR per min	15.6±4.4	15.8±4.6	15.9±4.4
IARS	5.0 [4.0;6.0]	6.0 [4.0;6.5]**	5.0 [4.0;6.0]
RMSSD, msec	25.0 [13.0;66.0]	27.0 [12.0;57.0]	27.5 [13.5;60.5]
SDNN, msec	30.0 [19,0;55.0]	27.0 [18.5;49.5]	33.0 [23.0;52.5]
CV, %	3.5 [2.3;5.7]	3.4 [2.4;5.8]	4.0 [2.9;5.8]
Mean, msec	842.6±125.1*	843.7±119.6**	854.5±121.2
Mo, msec	838.9±117.0*	843.4±117.2**	854.9±111.6
TP, msec2	595.1 [226.5;1796.9]	483.0 [211.3;1828.6]	815.9 [299.6;1739.3]
PHF, %	46.3 [29.0;66.5]	51.3 [29.9;68.6]	47.2 [27.0;69.3]
PLF, %	27.7 [16.8;39.7]	27.9 [17.4;41.9]	28.8 [16.9;39,7]
PVLF, %	20.0 [7.8;31.0]	14.2 [7.6;30.3]**	22.7 [11.4;34,9]
LF/HF	0.6 [0.3;1.2]	0.6 [0.3;1.4]	0.7 [0.3;1.2]
IC	1.2 [0.5;2.5]	1.0 [0.5;2.4]	1.1 [0.4;2.7]

Note: * – p<0.05 in comparison of initial data with period of recovery; ** – p<0.05 in comparison of the data during the test and in the period of recovery, Note: RMSSD – root-mean-square difference between duration of neighboring RR intervals; SDNN – standard deviation of NN intervals, reflects the total effect of autonomic regulation of heart rhythm; CV – coefficient of variation; TP – total power of spectrum; PHF – relative power of high-frequency oscillations; PLF – relative power of low-frequency oscillations;  PVLF – relative power of ‘very’ low-frequency oscillations; LF/HF – proportion of sympathetic and parasympathetic influence on the heart rhythm; IC – index of centralization

 

Statistically significant differences were obtained in the group of patients with COPD in HR, Mean and Mo parameters in the initial period and the period of recovery. Here, in the studied period HR decreased, while Mean and Mo, on the contrary, showed a statistically significant growth (p<0.05). Comparison of the parameters in the test and in the period of recovery showed buildup of Mean, Mo and power of ‘very’ low frequency range (PVLF). HR and IARS values in the analyzed period decreased (p<0.05). No statistically significant changes were noted in comparison of the initial parameters and those recorded during the test.

To compare changes between CIG parameters in the test with external peripheral vascular occlusion in patients with COPD and control group (volunteers without respiratory diseases), these parameters were also analyzed in the control group (Table 3).

Comparison of data between the initial period and the period of recovery showed statistically significant decrease in HR, IARS, power of high-frequency range (PHF). The parameters of the total effect of the autonomic regulation (SDNN), coefficient of variation (CV), Mean, Mo, total power of spectrum (TP), power of low-frequency range (PLF), index of centralization (IC) showed a statistically significant increase (p<0.05). According to the data of R.M. Baevsky, the obtained changes are explained by reduction of sympathetic and growth of parasympathetic influence in the regulation of the heart rhythm [7, 11].

 

Table 3 Comparative Analysis of Parameters of Heart Rate Variability in Evaluation of Ergoreflex  in Group of Volunteers with no Diseases of Respiratory Organs

Parameter	Control Group (n=41)
	Initially	In the test	After the test
HR, beat/min	69.8±8.9*	70.5±9.2**	68.6±8.4
RR per min	14.8±4.3	14.1 [10.8;16.8]	14.4±4.2
IARS	4.0 [4.0;6.0]*	5.0 [3.0;6.0]**	4.0 [3.0;5.0]
RMSSD, msec	14.0 [10.0;25/0]	16.0 [10.0;25.0]	14.0 [11.0;22.0]
SDNN, msec	23.0 [17.0;31.0]*^	27.0 [17.0;37.0]	27.0 [20.0;37.0]
CV, %	2.6 [2.0;3.6]*^	3.1 [2.2;4.3]	3.0 [2.1;4.1]
Mean, msec	873.4±113.4*	866.4±116.6**	887.7±112.4
Mo, msec	873.7±116.6*	865.8±118.4**	890.2±113.7
TP, msec2	344.4 [185.8;825.2]*	451.1 [243.2;940.9]	597.3 [327.7;1051.2]
PHF, %	29.7 [14.5;46.4]*	23.6 [15.4;38.3]	24.1 [17.2;31.2]
PLF, %	34.4 [25.3;42.3]^	43.9 [28.9;52.3]	35.9 [29.0;44.2]
PVLF, %	27.9 [19.8;47.6]	26.1 [17.4;39.7]**	37.3 [32.0;49.0]
LF/HF	1.4 [0.6;2.8]	2.1 [0.9;2.7]	1.7 [1.0;2.8]
IC	2.4 [1.2;5.9]*	3.2 [1.6;5.5]	4.1 [2.2;5.6]

Note: * – p<0.05 in comparison of initial data with period of recovery; ** – p<0.05 in comparison of the data in the test and in the period of recovery, Note: RMSSD – root-mean-square difference between duration of neighboring RR intervals; SDNN – standard deviation of  NN intervals, reflects the total effect of autonomic regulation of heart rhythm; CV – coefficient of variation; TP – total power of spectrum; PHF – relative power of high-frequency oscillations; PLF – relative power of low-frequency oscillations; PVLF – relative power of ‘very’ low-frequency oscillations; LF/HF – proportion between sympathetic and parasympathetic influence of the heart rhythm; IC – index of centralization

 

Comparison of the data of the test and of the period of recovery showed decline of HR and IARS. Mean, Mo, and also PVLF parameters increased, here, Mean, Mo showed a tendency to higher values in the period of recovery in comparison with the group of patients with COPD. Besides, in comparison of the initial data with the period of test, statistically significant increase in values SDNN, CV, PLF was obtained in participants of the control group.

Conclusion

Thus, a study of the activity of ergoreflex by parameters of CIG showed the difference between groups of patients with COPD and respondents of the control group. In the test with external peripheral vascular occlusion, changes of CIG in the control group were more expressed, and many parameters showed statistically significant changes (p<0.05). In patients with COPD, very likely due to persistent hyperactivity of ergoreflex, the changes were less expressed and not always reached statistically significant level (p>0.05).

About the authors

Aleksey V. Kosyakov

Ryazan State Medical University

Author for correspondence.
Email: Kosyakov_alex@rambler.ru
ORCID iD: 0000-0001-6965-5812
SPIN-code: 8096-5899
ResearcherId: X-2649-2018

Assistant of the Department of Hospital Therapy with the Course of Medico-social Examination

Russian Federation, 390026 g. Ryazan', ul. Vysokovol'tnaya, d. 9

Vladimir N. Abrosimov

Ryazan State Medical University, Ryazan

Email: Kosyakov_alex@rambler.ru
ORCID iD: 0000-0001-7011-4765
SPIN-code: 3212-4620
ResearcherId: S-2818-2016

MD, PhD, Professor, Head of the Department of Therapy and Family Medicine of Post-graduate Education Faculty with the Course of Medico-social Examination

Russian Federation, 390026 g. Ryazan', ul. Vysokovol'tnaya, d. 9

References

Supplementary files