Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure

Abstract

Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to -40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR↔SBP and RR↔MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR→SBP and RR→MAP) showed a significantly (p < 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP→RR and MAP→RR). In response to moderate category hemorrhage (-30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR→SBP (p = 0.76), RR→MAP (p = 0.60), and SBP→RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP→RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP→RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression.

Keywords: arterial blood pressure; baroreflex; blood loss; causality; central hypovolemia; heart rate; hemorrhage.

Figure 1

The response of cardiovascular parameters to graded lower-body negative pressure. R-R intervals (A) reduced significantly both at −30 (p = 0.001) and −40 (p < 0.001) mmHg LBNP compared to rest. Pulse pressure (B) reduced significantly (p = 0.001) at −40 mmHg compared to rest. Additionally, both R-R intervals (p < 0.001) and pulse pressure (p = 0.02) reduced significantly at −40 mmHg LBNP compared to −20 mmHg LBNP. The systolic blood pressure (B), diastolic blood pressure (B), and the mean arterial pressure (B) did not change (p = 0.50, p = 0.79, and p = 0.99, respectively) in response to graded lower-body negative pressure, ^* and ^†represents significant change (p < 0.05, post-hoc result) compared to rest and −20 mmHg, respectively.

Figure 2

The response of baroreflex (A,C) and non-baroreflex (B,D) causalities to graded lower-body negative pressure. In response to LBNP, MAP→RR (p = 0.004) causality increased significantly at −30 mmHg compared to rest, SBP→RR (p = 0.001) causality increased significantly at −40 mmHg compared to rest. Compared to −20 mmHg the SBP→RR (p = 0.04) and MAP→RR (p = 0.01) causality increased significantly at −40 mmHg LBNP. No change in RR→SBP (p = 0.76) and RR→MAP (p = 0.60) causality was observed in response to LBNP. ^*Represents significant difference (p < 0.05, post-hoc result) from rest while ^†represents significant difference from −20 mmHg.

Figure 3

Comparison of non-baroreflex or feedforward (RR→SBP and RR→MAP) and baroreflex or feedback (SBP→RR and MAP→RR) causalities during supine baseline. The feedforward causality was significantly stronger (p < 0.001) than the feedback causality for both RR↔SBP (A) and RR↔MAP (B) interactions. ^*Represents significantly (p < 0.05, one-way ANOVA) stronger causality.

Figure 4

Percent (%) change in MAP→RR causality in response to −30 mmHg LBNP compared to rest. Out of 27 participants, 22 showed an increase, 2 participants showed a decline, and 3 participants did not show a change in MAP→RR causality at moderate LBNP compared to rest.