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Background: Alteration of cardiac autonomic function may underlie the link between hypnotics use and the risk for cardiovascular morbidity and mortality. This study aimed to examine the relationship between the various characteristics of benzodiazepine receptor agonists (BzRAs) and heart rate variability (HRV).Methods: A community-based survey using the cohort from the Yilan Study, Taiwan was conducted. Older adults aged 65 and older were randomly selected to participate from August 2013 to November 2016. Cardiac autonomic function was evaluated using HRV, and the lowest quartiles of HRV parameters were defined as unhealthy. Those who used BzRAs as a sleep aid were defined as BzRA hypnotic users. The characteristics of BzRA use were further detailed and included the half-life, drug compound, frequency of use, and cumulative daily equivalent dosage.Results: Of all participants, 379 (14.5%) were BzRA hypnotic users. After controlling for covariates, BzRA hypnotic users had a higher risk for unhealthier HRV than non-users. Among all BzRA hypnotic users, those who only used benzodiazepines (BZDs), used short half-life BzRAs, and used the middle tertile of daily cumulative BZD equivalent had a higher risk for poor total power (odds ratio [OR]: 2.11, 95% confidence interval [CI]: 1.07-4.16), high frequency (OR: 3.43, 95% CI: 1.07-10.97), and high frequency (OR: 2.94, 95% CI: 1.35-6.42), respectively, than their counterparts.Conclusions: BzRA hypnotics are linked with poor cardiac autonomic function. Various characteristics of BzRA hypnotics showed an independent pattern of association with cardiac autonomic function. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are critical for anti-bacterial activity of the innate immune system. We have previously shown that mitochondrial damage-associated molecular patterns (mtDAMPs), including mitochondrial DNA (mtDNA), are released into the circulation after injury. We therefore questioned whether mtDNA is involved in trauma-induced NET formation. Treatment of human polymorphoneutrophils (PMN) with mtDNA induced robust NET formation, though in contrast to phorbol myristate acetate (PMA) stimulation, no NADPH-oxidase involvement was required. Moreover, formation of mtDNA-induced NETs was completely blocked by TLR9 antagonist, ODN-TTAGGG. Knowing that infective outcomes of trauma in elderly people are more severe than in young people, we measured plasma mtDNA and NET formation in elderly and young trauma patients and control subjects. MtDNA levels were significantly higher in the plasma of elderly trauma patients than young patients, despite lower injury severity scores in the elderly group. NETs were not visible in circulating PMN isolated from either young or old control subjects. NETs were however, detected in PMN isolated from young trauma patients and to a lesser extent from elderly patients. Stimulation by PMA induced widespread NET formation in PMN from both young volunteers and young trauma patients. NET response to PMA was much less pronounced in both elderly volunteers’ PMN and in trauma patients’ PMN. We conclude that mtDNA is a potent inducer of NETs that activates PMN via TLR9 without NADPH-oxidase involvement. We suggest that decreased NET formation in the elderly regardless of higher mtDNA levels in their plasma may result from decreased levels of TLR9 and/or other molecules, such as neutrophil elastase and myeloperoxidase that are involved in NET generation. Further study of the links between circulating mtDNA and NET formation may elucidate the mechanisms of trauma-related organ failure as well as the greater susceptibility to secondary infection in elderly trauma patients. [ABSTRACT FROM AUTHOR]