Comparison of heart rate variability, hemodynamic, metabolic and inflammatory parameters in various phases of decompansatory hemorrhagic shock of normal and vagotomized conscious male rats

Abstract

Background: Heart rate variability (HRV) analysis has shown promise as a valuable complementary tool for clinical assessment in trauma cases. This study aims to evaluate the utility of HRV in monitoring different severities of hemorrhagic shock (HS) and its correlation with traditional hemodynamic and metabolic parameters.

Methods: Male Sprague-Dawley rats were divided into different experimental groups, including those with and without vagotomy, and were exposed to different classes of decompensatory HS. To induce varying severities of HS, volume resuscitation was delayed by gradually returning 0%, 20%, or 50% of the shed blood volume at the end of the compensation phase, referred to as 0% DFR, 20% DFR, and 50% DFR class, respectively. Hemodynamic parameters were monitored, and HRV was calculated. Levels of TNF-α and IL-10 were determined in lung tissue at the end of the experiments. Correlations between HRV, hemodynamic parameters, inflammatory gene expression and arterial blood gas variables were evaluated.

Results: HRV showed increased power of the low-frequency (LF) and respiratory sinus arrhythmia (RSA) in all groups during the hypotension phase of HS (Nadir 1). Subdiaphragmatic vagotomy blunted the increase in the LF component in the Nadir 1. After volume resuscitation, systolic blood pressure (SBP), RSA and LF returned to baseline in the 0% DFR and 20% DFR classes. However, animals in 50% DFR class exhibited a reduced SBP and LF and lower pH. Notably, strong correlations were found between LF and SBP as well as tissue hypoperfusion markers. The expression of TNF-α in the lung was increased in all HS groups, while this gene expression was significantly higher in the vagotomized animals.

Conclusion: The alterations in HRV components were found to be significantly correlated with the hemodynamic and metabolic status of the animals, while showing no association with inflammatory responses. Additionally, the intervention of subdiaphragmatic vagotomy significantly impacted both HRV components and inflammatory responses. Collectively, these findings suggest the potential of HRV components for the assessment of the presence and severity of HS.

Keywords: Decompensatory shock; Heart rate variability; Subdiaphragmatic vagotomy; TNF-α.

Fig. 1

Schedule of experimental procedures in sham treatment, delayed fluid resuscitation (DFR), vagotomy (Vag), and Vag + DFR groups. The animals bled until their mean arterial pressure (MAP) reached 35 ± 5 mm Hg, which was maintained until the compensation endpoint was reached—the point at which returning the shed blood became necessary to sustain the MAP. This initial phase, referred to as Nadir 1, lasted about 25 min. After this, during the second phase called Nadir 2, which lasted about 45 min, different amounts of the maximum shed blood were returned. For the 0% DFR class, 100% of the blood was returned continuously, while for the 20% DFR and 50% DFR classes, 20% and 50% of the blood was returned gradually, respectively. Subsequently, the rats were resuscitated with the remaining blood plus 20% and 50% of the blood collected as Lactated Ringer's Solution within 10 min in the 20% DFR and 50% DFR classes, respectively. ABG: arterial blood gas analysis, MAP: mean arterial pressure, RL: Ringer's lactate

Fig. 2

The diastolic blood pressure (DBP, A), systolic blood pressure (SBP, B), heart period (HP, C), respiratory sinus arrhythmia (RSA, D) and low frequency (LF, E) in the Sham (n = 7), Vag (n = 7), HS 0% (n = 6) and Vag + HS 0% (n = 9), HS 20% (n = 6), Vag + HS 20% (n = 10), HS 50% (n = 9) and Vag + HS 50% (n = 6) groups. Hemorrhagic shock (HS) increases both RSA and LF components, alongside a reduction in BP measurements. Vagotomy blunts the changes in LF induced by HS. Data are mean ± SE. *P < 0.05 vs. the sham group; #p < 0.05 vs. the Vag group. Groups were compared using ANOVA with Tukey’s post hoc test

Fig. 3

The diastolic blood pressure (DBP, A), systolic blood pressure (SBP, B), heart period (HP, C), respiratory sinus arrhythmia (RSA, D) and low frequency (LF, E) in the Sham (n = 7), Vag (n = 7), HS 0% (n = 6) and Vag + HS 0% (n = 9), HS 20% (n = 6), Vag + HS 20% (n = 10), HS 50% (n = 9) and Vag + HS 50% (n = 6) groups. Volume resuscitation restored blood pressure components (A, B), reduced HP (C), and returned RSA and LF to normal levels in most HS and Vag + HS groups. However, in the HS 50% group, the combination of low SBP, high RSA, and low LF suggests ongoing hemodynamic instability. Similar patterns of low SBP and LF were also observed in the Vag + HS 50% group. Data are mean ± SE. ^*P< 0.05 vs. the sham group; ^#p < 0.05 vs. the Vag group; ^@P < 0.05 vs. the HS 0% group; ^¥p< 0.05 vs. the Vag + HS 0% group; ^&P< 0.05 vs. the HS 20% group; and ^£p< 0.05 vs. the Vag + HS 20% group. Groups were compared using ANOVA with Tukey’s post hoc test

Fig. 4

The expressions of TNF-α (A) and IL-10 (B) in lung in the Sham (n = 7), Vag (n = 7), HS 0% (n = 6) and Vag + HS 0%(n = 9), HS 20%(n = 6), Vag + HS 20%(n = 10), HS 50%(n = 9) and Vag + HS 50%(n = 6) groups. Data means ± SE. TNF-α gene expression in the lungs was elevated in all hemorrhagic shock (HS) groups, and vagotomy further increased this expression in the 20% and 50% DFR classes (A). IL-10 expression significantly increased only in the 20% DFR class. The comparison between groups was performed by using parametric one-way ANOVA and Tukey’s post hoc multiple-comparison test. ^*P < 0.05, versus the Sham group; ^#P < 0.05, versus the Vag, group; ^aP < 0.05, versus the HS 20% and ^bP < 0.05, versus the HS 50%