Changes in the autonomic cardiorespiratory activity in parturient women with severe and moderate features of preeclampsia

Abstract

Background: Cardiorespiratory coupling (CRC) is a physiological phenomenon that reflects the mutual interaction between the cardiac and respiratory control systems. It is mainly associated with efferent vagal activity from the central autonomic network. Few studies have explored the autonomic changes of CRC in preeclampsia, a critical obstetric complication related to possible autonomic dysfunctions and inflammatory disturbances. This study examined the autonomic mechanisms of CRC in women with severe and moderate preeclampsia and healthy controls by applying nonlinear methods based on information theory, such as mutual information (MI) and Renyi's mutual information (RMI) and the linear and nonlinear analysis of the Pulse-Respiration Quotient (PRQ).

Methods: We studied three groups of parturient women in the third trimester of pregnancy with a clinical diagnosis of preeclampsia without severe symptoms (P, 38.5 ± 1.4 weeks of pregnancy, n=19), preeclampsia with severe symptoms (SP, 37.5 ± 0.9 weeks of pregnancy, n=22), and normotensive control women (C, 39.1 ± 1.3 weeks of pregnancy, n=20). 10-minutes of abdominal electrocardiograms (ECG) and respiratory signals (RESP) were recorded in all the participants. Subsequently, we obtained the maternal beat-to-beat (RR) and breath-to-breath (BB) time series from ECG and RESP, respectively. The CRC between RR and BB was quantified by nonlinear methods based on information theory, such as MI and RMI, along with the analysis of the novel index of PRQ. Subsequently, we computed the mean PRQ (mPRQ) and the normalized permutation entropy (nPermEn_PRQ) from the PRQ time series generated from BB and RR. In addition, we examined the vagal activity in the three groups by the logarithm of the median of the distribution of the absolute values of successive RR differences (logRSA).

Results: The MI and RMI values were significantly lower (p<0.05) in the preeclamptic groups compared to the control group. However, no significant differences were found between the preeclamptic groups. The logRSA and nPermEn_PRQ indices were significantly lower (p<0.05) in SP compared to C and P.

Conclusion: Our data suggest that parturient women with severe and mild preeclampsia may manifest an altered cardiorespiratory coupling compared with normotensive control women. Disrupted CRC in severe preeclampsia could be associated with vagal withdrawal and less complex cardiorespiratory dynamics. The difference in vagal activity between the preeclamptic groups may suggest a further reduction in vagal activity associated with the severity of the disease.

Keywords: cardiorespiratory coupling; mutual information; pregnancy; pulse-respiration quotient; vagal withdrawal.

Figure 1

Experimental setup of data acquisition for maternal abdominal electrocardiograms (ECG) and respiratory signals (RESP).

Figure 2

Box plots of nonlinear methods based on information theory to evaluate the cardiorespiratory coupling (CRC) among healthy normotensive participants (C), preeclampsia without severe features (P), and preeclampsia with severe features (SP) groups. (A) mutual information (MI); (B) Renyi’s mutual information with a degree of divergence α = 2.5 (RMI); *p< 0.05, **p<0.01,***p<0.001 indicate significant differences by post-hoc LSD Fisher.

Figure 3

Box plots of the vagal-related index of the logarithm of the median of the distribution of the absolute values of successive RR differences (logRSA) for normotensive participants (C), preeclampsia without severe features (P), and preeclampsia with severe features (SP) groups. *p<0.05 indicates significant differences between P vs. SP by post-hoc LSD Fisher; **p<0.01 indicates significant differences between C vs. SP by post-hoc LSD Fisher.

Figure 4

Box plots of linear and nonlinear analysis of maternal Pulse-Respiration Quotient (PRQ) time series for normotensive participants (C), preeclampsia without severe features (P), and preeclampsia with severe features (SP) groups. (A) the mean value of the PRQ time series (mPRQ), (B) sample entropy (SampEn_PRQ), and (C) the normalized permutation entropy (nPermEn_PRQ). All these indices were calculated for the PRQ time series. *p<0.05 and **p<0.01 indicate significant differences by post-hoc LSD Fisher.

Figure 5

Preeclampsia may be considered a suitable model of high sympathetic and low parasympathetic activity, reduced heart rate complexity, and exacerbated inflammation, probably mediated by an increased tumor necrosis factor-α (TNF-α) and other pro-inflammatory factors cytokines. The potential dysregulation in the maternal cholinergic anti-inflammatory pathway (CAP) may be reflected as a decreased cardiorespiratory coupling (CRC) with concomitant vagal withdrawal. The linear and nonlinear analysis of the maternal beat-to-beat (RR) and breath-to-breath (BB) time series allows for noninvasively quantifying the efferent vagus nerve activity (related to the CAP) extracted from cardiorespiratory dynamics.