The Effects of Dexmedetomidine Post-Conditioning on Cardiac and Neurological Outcomes After Cardiac Arrest and Resuscitation in Swine

Abstract

Introduction: One of the main contents of post-resuscitation care is to alleviate cardiac and neurological damage in cardiac arrest (CA) victims. Recently, dexmedetomidine pre-and post-conditioning have been shown to both effectively protect the heart and brain against regional ischemia reperfusion injury. In this study, we investigated the effects of dexmedetomidine post-conditioning on cardiac and neurological outcomes after CA and resuscitation in swine. Methods: A total of 28 male domestic swine were randomized into four groups: sham, cardiopulmonary resuscitation (CPR), low-dose dexmedetomidine post-conditioning (LDP), and high-dose dexmedetomidine post-conditioning (HDP). Sham animals underwent the surgical preparation only. The animal model was established by 8 min of CA and then 5 min of CPR. After the animal was successfully resuscitated, a loading dose of 0.25 mg/kg of dexmedetomidine was intravenously injected followed by continuous infusion of 0.25 mg/kg/h for 6 h in the LDP group, and meanwhile a double dose of dexmedetomidine was similarly administered in the HDP group. The same amount of saline was given in the other two groups. All the resuscitated animals were monitored for 6 h and then returned to their cages for an additional 18 h of observation. Results: After resuscitation, significantly greater cardiac, neurological dysfunction, and injuries were observed in all animals experiencing CA and resuscitation when compared with the sham group. However, the severity of cardiac and neurological damage was significantly milder in the two dexmedetomidine-treated groups than in the CPR group. Dexmedetomidine postconditioning also significantly decreased post-resuscitation tissue inflammation, oxidative stress, and cell apoptosis and necroptosis in the heart and brain when compared with the CPR group. In addition, these protective effects produced by dexmedetomidine post-conditioning were significantly greater in the HDP group than in the LDP group. Conclusions: -Dexmedetomidine post-conditioning dose-dependently improved post-resuscitation cardiac and neurological outcomes through the inhibition of tissue inflammation, oxidative stress, and cell apoptosis and necroptosis.

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

“…Sun et al ( 50 ) indicate that DEX may preserve brain function and ultimately improve the outcome of sepsis by decreasing pyroptosis and subsequently protecting neurons. In Shen et al ( 51 ), DEX postconditioning also improves cardiac outcomes and neurological function following cardiac arrest and resuscitation in swine, partly by suppressing cell necroptosis. Zhao et al ( 25 ) report that DEX alleviates acute kidney injury by increasing autophagy through the modulation of the PI3K/AKT/mTOR pathway.…”

“…As shown in the present study, DEX alleviated neuroinflammation in mouse TBI models. Additionally, DEX directly regulates several cell death models (22,25,(48)(49)(50)(51). According to Gao et al (49), DEX induces the expression of the neuroglobin protein in hippocampal tissues and then inhibits neuronal apoptosis through the mitochondrial pathway.…”

Cardiac Arrest – An interdisciplinary scoping review of preclinical literature from 2020

“…In another study evaluating the use of dexmedetomidine, a drug that is already in common clinical practice, Shen et al examined the effects of dexmedetomidine on outcome postarrest given its α 2 -receptor agonist properties. Twenty-eight pigs undergoing an 8-minute cardiac arrest and 5-minute resuscitation, following AHA guidelines, were divided into control, low-dose and high-dose dexmedetomidine groups for post-arrest care [18]. Myocardial function, neurologic deficit score, and serum biomarkers of cardiac and cerebral injury were compared across all groups, with a suggestion of dose-dependent benefit to dexmedetomidine being seen [18].…”

“…Twenty-eight pigs undergoing an 8-minute cardiac arrest and 5-minute resuscitation, following AHA guidelines, were divided into control, low-dose and high-dose dexmedetomidine groups for post-arrest care [18]. Myocardial function, neurologic deficit score, and serum biomarkers of cardiac and cerebral injury were compared across all groups, with a suggestion of dose-dependent benefit to dexmedetomidine being seen [18]. This study expands on a previous study in rats, and while the lack of histologic evaluation and typical limitations of using otherwise healthy animals to model cardiac arrest may limit the generalizability of these findings, human study may be feasible given the availability of dexmedetomidine as a sedative [18].…”

What's New in Shock, March 2021?

“…These data suggest that Buprenophrine may have confounding effects on studies of hemodynamics of shock and should be used with caution, and further, that NSAID therapy can provide adequate analgesia with less cardiovascular complications. Along this vein, Dr Shen et al (11) have evaluated the effects of Dexmedetomidine post-treatment on cardiovascular and neurological outcomes after cardiac arrest in swine. The authors show that after cardiac arrest, Dexmedetomidine treatment was associated with improved outcomes and that a high-dose regimen augmented these salutatory effects.…”