Heart rate and blood-pressure variability stratify hemorrhagic shock severity and reveal vagal-dependent autonomic–vascular coupling: a controlled rat study

Background Hemorrhagic shock (HS) is a leading cause of preventable trauma mortality, with most deaths occurring within hours of injury. Early identification of the transition from compensatory to decompensatory shock remains challenging because conventional vital signs often remain within normal ranges until late stages. Beat-to-beat heart rate variability (HRV) and blood pressure variability (BPV), obtainable from continuous arterial waveforms, reflect dynamic autonomic regulation and may provide earlier indicators of physiological decompensation. We investigated whether peripheral autonomic and hemodynamic markers can non-invasively stratify HS severity and whether vagal integrity modulates these predictive signatures. Methods Male Sprague–Dawley rats were subjected to graded hemorrhagic shock using a delayed fluid resuscitation (DFR) paradigm and classified as moderate (20% DFR) or severe (50% DFR) hemorrhagic shock, defined by delayed fluid resuscitation volume. Animals were assigned to non-vagotomized (HS) and subdiaphragmatic vagotomized (Vag+HS) groups. Heart rate variability (HRV), blood pressure variability (BPV), heart period (HP), and vagal efficiency (VE) were derived from arterial pressure recordings obtained during steady state (pre-hemorrhage) and the early compensatory nadir phase. Stepwise linear discriminant function analysis was used to develop predictive models of shock severity. Model performance was assessed using classification accuracy, cross-validation, and receiver operating characteristic (ROC) analysis. Results In non-vagotomized animals, a model incorporating HRV and BPV measures classified moderate versus severe HS with 93.3% accuracy (cross-validated accuracy 86.7%). High-frequency diastolic BP variability during nadir and systolic pressure dynamics were the strongest discriminators. In vagotomized animals, the model showed apparent complete separation in this dataset (AUC=1.00), which should be interpreted cautiously given the sample size. In vagotomized animals, a broader combination of autonomic and hemodynamic features, including low-frequency variability during steady state, vagal efficiency, and heart period dynamics, complete separation between shock severity groups on ROC analysis. Regression analysis demonstrated a significant association between pre-shock sympathetic modulation and impaired post-resuscitation baroreflex sensitivity in intact animals, a relationship that was absent after vagotomy, indicating disruption of autonomic–vascular coupling. Conclusions Continuous analysis of HRV and BPV enables accurate stratification of hemorrhagic shock severity during early compensatory phases. Vagal integrity modifies the structure of predictive autonomic signatures during hemorrhage. These findings support further evaluation of variability-based analytics as an adjunct to continuous ICU waveform monitoring to identify patients at risk of hemodynamic deterioration before overt hypotension develops.