Endotracheal tube-induced sore throat pain and inflammation is coupled to the release of mitochondrial DNA

In the absence of infection, the pathophysiology of endotracheal tube-induced sore throat pain is unclear. Activated neutrophils release elastase, reactive oxygen species, and inflammatory cytokines known to contribute to neuropathic pain. Sterile tissue injury can cause the release of damage-associated molecular patterns such as mitochondrial DNA that promote neutrophil activation. We hypothesized that endotracheal tube-induced sore throat pain is linked to mitochondrial DNA-mediated neutrophil inflammation. A nonrandomized prospective survey for sore throat pain was conducted in 31 patients who required short-term intubation and had no evidence of upper airway infection. Patterns of neutrophil abundance, activation, and mitochondrial DNA levels were analyzed in tracheal lavage fluid following intubation and prior to extubation. Thirteen of 31 patients reported sore throat pain. Sore throat patients had high neutrophilia with elevated adhesion molecule and TLR9 expression and constitutive reactive oxygen species generation. Tracheal lavage fluid from sore throat patients accumulated mitochondrial DNA and stimulated neutrophils to release mediators associated with pain in a TLR9- and DNAse-dependent fashion. Endotracheal tube-induced sore throat is linked to the release of mitochondrial DNA and can drive TLR9-mediated inflammatory responses by neutrophils reported to cause pain. Mitigating the effects of cell-free mitochondrial DNA may prove beneficial for the prevention of endotracheal tube-mediated sore throat pain

Pressor response induced by clenbuterol treatment in immobilized normotensive rats

Short-term treatment with clenbuterol [0.6 mg/kg-1 subcutaneously (s.c.) daily] produces a pressor effect in stressed rats after a period of immobilization (40 min). The stress applied markedly increases the plasma concentrations of norepinephrine (NE) and epinephrine. After bilateral adrenal demedullation, the increased levels of catecholamines and the hypertensive response obtained after clenbuterol treatment in the stressed animals were reduced to the values of the control rats. Clenbuterol treatment produced desensitization of the β2-adrenoceptor-mediated effect and thus reduced the vasodilator response induced by isoproterenol and increased the vasoconstriction produced by epinephrine but not that caused by NE. This desensitization may be responsible for the hypertensive response after clenbuterol treatment in stressed animals which is attenuated after adrenal demedullation. In conclusion, our results provide evidence that clenbuterol treatment induces pressor effect in normotensive animals under stress

Further evidence of interaction between vasodilator β\u3csub\u3e2\u3c/sub\u3e- and vasoconstrictor α\u3csub\u3e2\u3c/sub\u3e-adrenoceptor-mediated responses in maintaining vascular tone in anesthetized rats

The importance of the interaction of α- and β-adrenoceptors in maintaining vascular tone in rats was studied. This interaction after clenbuterol (CLEN) treatment indicates an important contribution of the circulating epinephrine (EPI) levels. In urethane-anesthetized rats, the β2-adrenoceptor antagonist (CI 118.551 was more effective in antagonizing isoproterenol-induced hypotension (mainly β2-mediated) than tachycardia (mainly β1-mediated). Intravenous (i.v.) administration of the α2-adrenoceptor agonist clonidine (CLO) induced an initial pressor response followed by a more prolonged hypotension and bradycardia. The initial hypertensive effect was potentiated by previous acute administration of ICI 118.551 as well as by the nonselective β-adrenoceptor antagonist propranolol, but not by metoprolol, a more selective β1-blocker. Fourteen days of administration of the β2-adrenoceptor agonist CLEN [0.3 mg/kg, subcutaneously (s.c.) twice daily], a treatment that induces desensitization of β2-mediated vasodilation, increased the pressor response induced by CLO, an effect that was not observed in pentobarbital-anesthetized rats. In any case, neither β-blockers nor CLEN treatment affects the hypotension and bradycardia induced by CLO. Mean blood pressure (BP) of CLEN-treated rats was increased under urethane anesthesia but not under pentobarbital anesthesia. Catecholamine levels (principally EPI) were higher in urethane-anesthetized rats. These results provide further evidence of a functional interaction between α2- and β2-adrenoceptor-mediated responses in rat vasculature and suggest that vasodilator β2-adrenoceptors might contribute to the determination of peripheral vascular tone when circulating EPI is substantially elevated