aconitine and Pulmonary-Edema

Infectious complications, predominantly pneumonia, are the most common cause of death in the postacute phase of stroke, although the mechanisms underlying the corresponding immunosuppression are not fully understood. We tested the hypothesis that activation of the α7 nicotinic acetylcholine receptor (α7nAChR) pathway is important in the stroke-induced increase in lung injury caused by Pseudomonas aeruginosa pneumonia in mice. Prior stroke increased lung vascular permeability caused by P. aeruginosa pneumonia and was associated with decreased lung neutrophil recruitment and bacterial clearance in mice. Pharmacologic inhibition (methyllycaconitine IC(50): 0.2-0.6 nM) or genetic deletion of the α7nAChR significantly (P<0.05) attenuates the effect of prior stroke on lung injury and mortality caused by P. aeruginosa pneumonia in mice. Finally, pretreatment with PNU-282987, a pharmacologic activator of the α7nAChR (EC(50): 0.2 μM), significantly (P<0.05) increased lung injury caused by P. aeruginosa pneumonia, significantly (P<0.05) decreased the release of KC, a major neutrophil chemokine, and significantly (P<0.05) decreased intracellular bacterial killing by a mouse alveolar macrophage cell line and primary mouse neutrophils. In summary, the α7 nicotinic cholinergic pathway plays an important role in mediating the systemic immunosuppression observed after stroke and directly contributes to more severe lung damage induced by P. aeruginosa.

Topics: Aconitine; Adrenergic beta-Antagonists; alpha7 Nicotinic Acetylcholine Receptor; Animals; Benzamides; Bridged Bicyclo Compounds; Cell Line; Disease Models, Animal; Immune Tolerance; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Nicotinic Agonists; Nicotinic Antagonists; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Pulmonary Edema; Receptors, Nicotinic; Signal Transduction

"Torikabuto" is a kind of plant which contains deadly poison. Its ingredient is aconitine alkaloids. We report a case of aconitine poisoning with fatal arrhythmia and acute pulmonary edema who was saved with cardio pulmonary bypass. A 41-year-old male ate to mistake "Torikabuto" for wild plant. He developed symptoms of dysarthria and admitted to our hospital. He developed ventricular tachycardia and fibrillation soon after his admission. Then he developed cardiogenic shock. He was resuscitated and supported with a percutaneous cardio pulmonary bypass. Ventricular tachycardia disappeared 24 hours after admittion. About 1 week later, cardio pulmonary bypass was terminated and about 3 months later, he discharged from our hospital.

Topics: Aconitine; Acute Disease; Adult; Cardiopulmonary Bypass; Humans; Male; Plant Poisoning; Plants, Toxic; Pulmonary Edema; Tachycardia, Ventricular; Treatment Outcome

Bilateral injections of aconitine in the preoptic-anterior hypothalamic area in rats produces pulmonary edema that is mediated by neurogenic mechanisms. The aim of the present study was to determine the efficacy of hypovolemia or intravenous methylprednisolone on preventing aconitine-induced pulmonary edema. Rats made hypovolemic before or after injection of aconitine or treated with 40 mg/kg methylprednisolone had normal lung weight-to-body weight ratios (LW/BW) and normal pulmonary ultrastructure. In contrast, high LW/BW and gross ultrastructural alterations were noted in rats injected with aconitine only. These findings suggest that hypovolemia was effective in preventing aconitine-induced neurogenic pulmonary edema (NPE) because it lowered the pulmonary blood volume and that methylprednisolone provided a beneficial effect by suppressing the hemodynamic response involved in NPE or by directly stabilizing the cell membranes.

Topics: Aconitine; Aconitum; Animals; Blood Pressure; Blood Volume; Female; Lung; Methylprednisolone; Methylprednisolone Hemisuccinate; Pulmonary Edema; Rats

Topics: Aconitine; Animals; Capillary Permeability; Dose-Response Relationship, Drug; Female; Lung; Microscopy, Electron; Pulmonary Alveoli; Pulmonary Edema; Rats

Topics: Aconitine; Aconitum; Atropine; Autonomic Nerve Block; Blood Pressure; Blood Pressure Determination; Hypothalamus; Pharmacology; Phenoxybenzamine; Phentolamine; Pulmonary Circulation; Pulmonary Edema; Rats; Research; Toxicology

Topics: Aconitine; Aconitum; Humans; Pulmonary Edema