The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor α (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.

Effects of the combination α_2-adrenergic receptor agonist and k-opioid receptor agonist on post-resuscitation cardiac function in rabbits / 中华急诊医学杂志

Objective To investigate the effects of α_2-adrenergic receptor agonist and k-opioid receptor agonist jointly used on hemodynamics and B-type natriuretic peptide in rabbits,and to explore the effective methods for lessensing post-resuscitation myocardial dysfunction.Method After the establishment of cardiopulmonary resuscitation (CPR) model in rabbits, 30 rabbits were randomly divided into 5 groups, namely epinephrine group(E), vasopressin group(V), U50488H group(U), mivazerol group(M) and mivazerol + U50488H group(M + U). Hemodynamics and B-type natriuretic peptide were examined before ventricular fibrillation and in the early stage of post CPR (30-240 min). Statistical analysis was performed with ANOVA techniques. Results (1)MAP,peak - dp/dt and peak + dp/dt in M + U group were significantly higher than those in other groups, and the increase of LVEDP was less than that in other groups (P<0.05).(2)The concentration of BNP in M + U group was significantly decreased than that in other groups (P <0.01 or P <0.05). Conclusions The α_2-adrenergic receptor agonist (mivazerol) and k-opioid receptor agonist used together can improve post CPR hemodynamics and reduce the concentration of B-type natriuretic peptide, lessening the post CPR myocardial dysfunction.