Dexmedetomidine compared to low-dose ketamine better protected not only the brain but also the lungs in acute ischemic stroke.

BACKGROUND: Dexmedetomidine (DEX) and low-dose ketamine (KET) present neuroprotective effects in acute ischemic stroke (AIS); however, to date, no studies have evaluated which has better protective effects not only on the brain but also lungs in AIS. METHODS: AIS-induced Wistar rats (390 ± 30 g) were randomized after 24-h, receiving dexmedetomidine (STROKE-DEX, n = 10) or low-dose S(+)-ketamine (STROKE-KET, n = 10). After 1-h protective ventilation, perilesional brain tissue and lungs were removed for histologic and molecular biology analysis. STROKE animals (n = 5), receiving sodium thiopental but not ventilated, had brain and lungs removed for molecular biology analysis. Effects of DEX and KET mean plasma concentrations on alveolar macrophages, neutrophils, and lung endothelial cells, extracted primarily 24-h after AIS, were evaluated. RESULTS: In perilesional brain tissue, apoptosis did not differ between groups. In STROKE-DEX, compared to STROKE-KET, tumor necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1) expressions were reduced, but no changes in nuclear factor erythroid 2-related factor-2 (Nrf2) and super oxide dismutase (SOD)-1 were observed. In lungs, TNF-α and VCAM-1 were reduced, whereas Nrf2 and SOD-1 were increased in STROKE-DEX. In alveolar macrophages, TNF-α and inducible nitric oxide synthase (M1 macrophage phenotype) were lower and arginase and transforming growth factor-ß (M2 macrophage phenotype) higher in STROKE-DEX. In lung neutrophils, CXC chemokine receptors (CXCR2 and CXCR4) were higher in STROKE-DEX. In lung endothelial cells, E-selectin and VCAM-1 were lower in STROKE-DEX. CONCLUSIONS: In the current AIS model, dexmedetomidine compared to low-dose ketamine reduced inflammation and endothelial cell damage in both brain and lung, suggesting greater protection.

Sevoflurane, Compared With Isoflurane, Minimizes Lung Damage in Pulmonary but Not in Extrapulmonary Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: Volatile anesthetics modulate inflammation in acute respiratory distress syndrome (ARDS). However, it is unclear whether they act differently depending on ARDS etiology. We hypothesized that the in vivo and in vitro effects of sevoflurane and isoflurane on lung damage would not differ in pulmonary (p) and extrapulmonary (exp) ARDS. METHODS: Twenty-four Wistar rats were randomized to undergo general anesthesia (1-2 minutes) with sevoflurane and isoflurane. Animals were then further randomized to receive Escherichia coli lipopolysaccharide (LPS) intratracheally (ARDSp) or intraperitoneally (ARDSexp), and 24 hours after ARDS induction, they were subjected to 60 minutes of sevoflurane or isoflurane anesthesia at 1 minimal alveolar concentration. The primary outcome measure was interleukin (IL)-6 mRNA expression in lung tissue. Secondary outcomes included gas exchange, lung mechanics, histology, and mRNA expression of IL-10, nuclear factor erythroid 2-related factor-2 (Nrf2), surfactant protein (SP)-B, vascular cell adhesion molecule-1, epithelial amiloride-sensitive Na-channel subunits α and γ, and sodium-potassium-adenosine-triphosphatase pump subunits α1 (α1-Na,K-ATPase) and ß1 (ß1-Na,K-ATPase). Additional ARDSp and ARDSexp animals (n = 6 per group) were anesthetized with sodium thiopental but not mechanically ventilated (NV) to serve as controls. Separately, to identify how sevoflurane and isoflurane act on type II epithelial cells, A549 human lung epithelial cells were stimulated with LPS (20 µg/mL) for 24 hours, and SP-B expression was quantified after further exposure to sevoflurane or isoflurane (1 minimal alveolar concentration ) for 60 minutes. RESULTS: In ARDSp, sevoflurane reduced IL-6 expression to a greater degree than isoflurane (P = .04). Static lung elastance (P = .0049) and alveolar collapse (P = .033) were lower in sevoflurane than isoflurane, whereas Nrf2 (P = .036), SP-B (P = .042), and ß1-Na,K-ATPase (P = .038) expressions were higher in sevoflurane. In ARDSexp, no significant differences were observed in lung mechanics, alveolar collapse, or molecular parameters between sevoflurane and isoflurane. In vitro, SP-B expression was higher in sevoflurane than isoflurane (P = .026). CONCLUSIONS: Compared with isoflurane, sevoflurane did not affect lung inflammation in ARDSexp, but it did reduce lung inflammation in ARDSp.