Effects of Pre-Cardiopulmonary Bypass Administration of Dexmedetomidine on Cardiac Injuries and the Inflammatory Response in Valve Replacement Surgery With a Sevoflurane Postconditioning Protocol: A Pilot Study.

BACKGROUND: Preventing myocardial ischemia-reperfusion injury in on-pump cardiac surgeries remains an enormous challenge. Sevoflurane postconditioning has been effective at overcoming this challenge by modulating inflammatory mediators and ameliorating antioxidative stress. Dexmedetomidine (DEX) is a commonly used medication for cardiac patients with organ-protective properties that lead to positive outcomes. Whether DEX also has cardiac-protective properties and the associated mechanism in sevoflurane postconditioning-based valve replacement surgeries are unknown. OBJECTIVE: This study was conducted to observe the effect of DEX administration before cardiopulmonary bypass (CPB) on myocardial injury, oxidative stress, and inflammatory response indicators in the peripheral blood. METHODS: Twenty-eight eligible cardiac patients who underwent valve replacement surgery with standard sevoflurane postconditioning were included in the study. The patients were randomly divided into a DEX group and a non-DEX group according to whether DEX (0.5-µg/kg overload dose for 10 minutes and a 0.5-µg/kg/h maintenance dose) or saline was administered from induction to the beginning of CPB. The primary outcome was the cardiac troponin I concentration (cTnI) in the blood 24 hours after CPB. The levels of malondialdehyde (MDA), superoxide dismutase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) were also measured. RESULTS: The mean cTnI at 24 hours after CPB was clearly decreased in the DEX group compared with that in the non-DEX group (4.16 ± 1.58 vs. 6.90 ± 3.73, P < 0.05). TNF-α levels were lower in the DEX group after CPB (T1-T5), with a significant difference found at 1-6 hours after CPB (1 hour, 19.03 vs. 28.09; 6 hours, 20.74 vs. 30.94, P < 0.05). The IL-6 and IL-8 concentrations in the DEX group were dramatically increased at 6 hours after CPB (P < 0.05). The MDA content and superoxide dismutase activity were comparable between the 2 groups. A lower proportion of anemia cases were noted after CPB in the DEX group than in the non-DEX group (non-DEX, 10% vs. DEX, 5%, P < 0.05). CONCLUSIONS: In valve replacement surgery with sevoflurane postconditioning, pre-CPB administration of DEX can reduce the cTnI level at 24 hours after CPB and brings synergic benefits of the inflammatory response.

Ketamine administration ameliorates anesthesia and surgery-induced cognitive dysfunction via activation of TRPV4 channel opening.

Perioperative neurocognitive disorder (PND) is a common complication associated with anesthesia and surgery in the elderly. The dysfunction of transient receptor potential vanilloid 4 (TRPV4) has been associated with a number of diseases, including Alzheimer's disease. Given that ketamine can reportedly improve PNDs, the present study sought to determine whether ketamine-induced PND alleviation was mediated by activation of TRPV4 channel opening. A total of 120, 20-month-old male C57BL/6 mice were randomly divided into five groups: Vehicle, PND (tibial fracture surgery), PND + ketamine (Ket), PND + Ket + HC-067047 (HC), and PND + HC groups. Ketamine (0.5 mg/kg) was administered intraperitoneally once a day for 3 days after surgery and HC-067047 (1 µmol/2 µl), an antagonist of TRPV4, was administered via the left lateral ventricle 30 min before ketamine treatment. Superoxide dismutase (SOD), malondialdehyde (MDA), lipid peroxidation (LPO), IL-1ß, IL-6, adenosine monophosphate-activated protein kinase (AMPK), NF-κB, TNF-α and IFN-ß levels were determined 3 days after surgery. At 28 days after surgery, fear conditioning and novel object recognition were assessed, and Aß1-42 levels were measured and ionized calcium binding adaptor molecule 1 (Iba1) staining was conducted on day 31 after surgery. The results revealed that ketamine administration upregulated total SOD activity, downregulated MDA and LPO content, mitigated phosphorylated (p)-NF-κB, TNF-α mRNA and IFN-ß mRNA expression in the hippocampus, and promoted p-AMPK 3 days after surgery. Furthermore, it was found that ketamine increased both context- and tone-dependent fear conditioning, and the time spent exploring a novel object, and reduced Aß peptide levels and microglial activation 30 days after surgery. Notably, these changes could be reversed by HC-067047 to a certain extent. In conclusion, ketamine improved PND in aged mice after tibial fracture surgery and the potential mechanism may involve activation of the TRPV4/AMPK/NF-κB signaling pathway.