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

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.