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Hemorrhagic shock causes vascular endothelial glycocalyx (EGCX) damage and systemic inflammation. Dexmedetomidine (DEX) has anti-inflammatory and EGCX-protective effects, but its effect on hemorrhagic shock has not been investigated. Therefore, we investigated whether DEX reduces inflammation and protects EGCX during hemorrhagic shock. Anesthetized Sprague-Dawley rats were randomly assigned to five groups (n=7 per group): no shock (SHAM), hemorrhagic shock (HS), hemorrhagic shock with DEX (HS+DEX), hemorrhagic shock with DEX and the α7 nicotinic type acetylcholine receptor antagonist methyllycaconitine citrate (HS+DEX/MLA), and hemorrhagic shock with MLA (HS+MLA). HS was induced by shedding blood to a mean blood pressure of 25-30 mmHg, which was maintained for 30 min, after which rats were resuscitated with Ringer's lactate solution at three times the bleeding volume. The survival rate was assessed up to 3 h after the start of fluid resuscitation. Serum tumor necrosis factor-alpha (TNF-α) and syndecan-1 concentrations, and wet-to-dry ratio of the heart were measured 90 min after the start of fluid resuscitation. The survival rate after 3 h was significantly higher in the HS+DEX group than in the HS group. Serum TNF-α and syndecan-1 concentrations, and the wet-to-dry ratio of heart were elevated by HS, but significantly decreased by DEX. These effects were antagonized by MLA. DEX suppressed the inflammatory response and serum syndecan-1 elevation, and prolonged survival in rats with HS.

Pentobarbital (PB) and ketamine (Ket) influence the concentration of neurotransmitters in the brain. PB has been reported to decrease the extracellular nitric oxide (NO) concentration through a decrease in acetylcholine (ACh) release, while Ket has been shown to increase the NO concentration via an increase in ACh release. Here, we investigated effects of PB and Ket on NO release and the relationship between NO and ACh in the rat striatum by in vivo microdialysis experiments. Male Sprague-Dawley rats were used. A microdialysis probe was inserted into the right striatum and perfused with modified Ringer's solution. Samples were collected every 15 min and injected into an HPLC system. The rats were freely moving, and PB and Ket were administered intraperitoneally. Neostigmine (1 and 10 µM) and mecamylamine (100 µM) were added to the perfusate. Calcium and magnesium concentrations were modified for each anesthetic to influence ACh release. PB decreased NO products (NOx) while Ket increased them. While perfusion with neostigmine showed no effect on baseline NOx concentrations, it diminished the PB-induced NOx reduction at low concentrations and abolished it at high concentrations. Magnesium-free perfusion had no effect on baseline NOx concentrations, whereas perfusion at a low magnesium concentration antagonized the PB-induced NOx reduction. Mecamylamine and calcium-free perfusion had no effect on baseline NOx concentrations and Ket-induced NOx increases. PB may decrease NO release through reduction in ACh release, whereas Ket may increase NO release independent of ACh regulation.

This study examined the sedative effect of, and hemodynamic response to dexmedetomidine administration in propofol-sedated swine. Sixteen swine were subjects. After anesthetic induction and preparation, the propofol infusion rate was adjusted to maintain a bispectral index (BIS) value between 55 and 65 (i.e., baseline). With the propofol infusion rate fixed at the baseline rate, dexmedetomidine was infused continuously at a rate of 0.2, 0.4, and 0.7 microg.kg(-1).h(-1) for one hour at each rate. The BIS value and hemodynamic parameters were recorded at each step. Dexmedetomidine decreased the BIS value, mean arterial blood pressure, heart rate, cardiac output, and mixed venous oxygen saturation in a dose-dependent manner. The systemic vascular resistance (SVR) did not change, but the pulmonary vascular resistance (PVR) increased. Oxygen delivery (DO(2)) and oxygen consumption (VO(2)) decreased. A small dose of dexmedetomidine (0.2 microg.kg(-1).h(-1)) greatly enhanced the sedative effects of propofol with only small changes in hemodynamics and systemic oxygen balance, suggesting it may be useful in reducing the propofol dose requirement. However, dexmedetomidine 0.4 microg.kg(-1).h (-1) suppressed cardiac contractility, and 0.7 microg.kg(-1).h(-1) induced hemodynamic instability and further systemic oxygen imbalance while the additional sedative effect was limited. A lower dose of dexmedetomidine may be recommended when using it in combination with propofol.