Abstract 32: A Novel Artificial Oxygen Carrier (Glycol-Modified Hemoglobin-Encapsulated Liposome; TRM645) Modulates Autonomic Control of the Heart during Hemorrhagic Shock Assessed by Heart Rate Variability
Many compensatory negative-feedback mechanisms, including autonomic nervous system activity, are involved in the pathophysiology of hemorrhagic shock, and heart rate variability (HRV) is a well-known index that reflects the autonomic control of the heart. The goal of the present study was to investigate the influence of hemorrhagic shock on autonomic nervous system activity and to characterize the therapeutic efficacy of the newly developed artificial oxygen carrier, glycol-modified hemoglobin-encapsulated liposome (TRM 645). An animal model of hemorrhagic shock was induced by withdrawing 20% of the total volume of blood from rats, and resuscitation was performed using TRM 645. A total of 21 Wistar rats were anesthetized under spontaneous respiration. Hemorrhagic shock was induced by aspirating blood, and rats subsequently received one of three different interventions: artificial oxygen carrier resuscitation (TRM 645 group, n = 7), saline resuscitation (Saline group, n = 7), or no treatment (Sham group, n = 7). Various HRV indices were measured, including low frequency spectra (LF, 0.04–0.15 Hz), high frequency spectra (HF, 0.15–0.40 Hz), and the ratio of low frequency spectra to high frequency spectra (LF/HF ratio), using monitoring electrocardiogram and the HRV MemCalc system. Further, temporal changes in HRV indices were observed for 60 min after resuscitation. LF spectra (0.03 ± 0.01 ms2/Hz vs. 0.22 ± 0.08 ms2/Hz and 0.12 ± 0.03 ms2/Hz, P < 0.05) and LF/HF ratio (0.05 ± 0.01 vs. 0.48 ± 0.18 and 0.80 ± 0.27, P < 0.05) following hemorrhagic shock were lower in the TRM 645 group when compared with the Sham and Saline groups. These data demonstrate that hemorrhagic shock induces significant changes in autonomic activity as assessed by HRV indices and that these changes can be attenuated by resuscitation with an artificial oxygen carrier (TRM 645). Therefore, TRM 645 has particular therapeutic efficacy in terms of autonomic control of the heart during resuscitation for hemorrhagic shock.