aconitine and Necrosis

This study investigated the protective effect of the compatibility of hypaconitine (HA) and glycyrrhetinic acid (GA) on H9c2 cells under oxygen and glucose deprivation (OGD)-induced injury, and the possible mechanisms. We found that HA+GA significantly improved pathology and morphology of the nucleus and ultrastructure of H9c2 cells under OGD as determined by Hoechst 33342 staining and transmission electron microscopy (TEM) tests. It also reduced the releases of lactate dehydrogenase (LDH), creatine kinase-myocardial band isoenzyme (CK-MB), and aspartate transaminase (AST) from the cultured supernatant of H9c2 cells, which were tested by enzyme-linked immune sorbent assay (ELISA) kits. In addition, it lessened the apoptotic rate as determined by a fluorescein isothiocyanate-annexin V/propidium iodide (FITC-AV/PI) double staining assay. It was also found that HA+GA might regulate the protein expression associated with the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Overall, the study demonstrated that HA+GA protected H9c2 cells against OGD-induced injury, and the signaling mechanism might be related to the PI3K/Akt signaling pathway.

Topics: Aconitine; Aconitum; Animals; Anti-Inflammatory Agents; Apoptosis; Cell Survival; Creatine Kinase, MB Form; Enzyme-Linked Immunosorbent Assay; Glucose; Glycyrrhetinic Acid; Heart Diseases; L-Lactate Dehydrogenase; Microscopy, Electron, Transmission; Necrosis; Oxygen; Phosphatidylinositol 3-Kinases; Rats; Signal Transduction

Amount evidence indicates that α7 nicotinic acetylcholine receptor (nAChRα7) activation reduces production of inflammatory mediators. This work aimed to verify the influence of endogenous nAChRα7 activation on the regulation of full-blown muscular inflammation in mdx mouse with Duchenne muscular dystrophy. We used mdx mice with 3 weeks-old at the height myonecrosis, and C57 nAChRα7(+/+) wild-type and nAChRα7(-/-) knockout mice with muscular injury induced with 60µL 0.5% bupivacaine (bp) in the gastrocnemius muscle. Pharmacological treatment included selective nAChRα7 agonist PNU282987 (0.3mg/kg and 1.0mg/kg) and the antagonist methyllycaconitine (MLA at 1.0mg/kg) injected intraperitoneally for 7 days. Selective nAChRα7 activation of mdx mice with PNU282987 reduced circulating levels of lactate dehydrogenase (LDH, a marker of cell death by necrosis) and the area of perivascular inflammatory infiltrate, and production of inflammatory mediators TNFα and metalloprotease MMP-9 activity. Conversely, PNU282987 treatment increased MMP-2 activity, an indication of muscular tissue remodeling associated with regeneration, in both mdx mice and WTα7 mice with bp-induced muscular lesion. Treatment with PNU282987 had no effect on α7KO, and MLA abolished the nAChRα7 agonist-induced anti-inflammatory effect in both mdx and WT. In conclusion, nAChRα7 activation inhibits muscular inflammation and activates tissue remodeling by increasing muscular regeneration. These effects were not accompanied with fibrosis and/or deposition of non-functional collagen. The nAChRα7 activation may be considered as a potential target for pharmacological strategies to reduce inflammation and activate mechanisms of muscular regeneration.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Benzamides; Bridged Bicyclo Compounds; Bupivacaine; Cell Death; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Male; Mice, Inbred C57BL; Mice, Inbred mdx; Mice, Knockout; Muscle, Skeletal; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; Necrosis; Nicotinic Agonists; Nicotinic Antagonists; Regeneration

The effect of injecting ethanol directly into the myocardium to control aconitine-induced ventricular tachycardia (VT) was evaluated in anesthetized dogs. In 17 dogs, VT was induced by injecting aconitine (1.0 microgram, median dose) directly into the epicardium. After inducing persistent VT for up to 3 min, 0.6 ml (median volume) of 96% ethanol was injected into the same epicardial region. Regular sinus rhythm reappeared in 15 dogs with no change in systolic blood pressure; the other 2 dogs died of ventricular fibrillation (VF). In another 13 dogs, VT was induced by injecting aconitine directly into the endocardium using a Variocath needle catheter. After persistent VT for up to 3 min, a regular sinus rhythm was restored in 7 dogs by injecting 2.0 ml (median volume) of 96% ethanol; the remaining 6 dogs died of VF. Histology showed no transmural necrosis and the subendocardial necrotic areas were essentially the same in the dogs that recovered from VT as in those that died. There was no statistically significant relationship between doses of ethanol and VT duration. These preliminary results suggest that the injection of ethanol into the myocardium may efficiently terminate VT when other techniques fail.

Topics: Aconitine; Animals; Dogs; Electrocardiography, Ambulatory; Endocardium; Ethanol; Female; Injections; Male; Myocardium; Necrosis; Tachycardia, Ventricular

In 15 anesthetized dogs, a diagonal branch of the left anterior descending coronary artery was cannulated. Localized ventricular tachycardia (VT) was induced by injecting aconitine solution into the left ventricular wall perfused by the cannulated diagonal branch. In 6 untreated control dogs, VT lasted 17.6 +/- 8.3 minutes, 3 of them degenerated into ventricular fibrillation. The VTs were eliminated in 8 of the 9 dogs (88.9%) 1.2 +/- 1.4 minutes after injection of 96% ethyl alcohol. The pathologic examination revealed that transmural myocardial necrosis was present in 7 of 9 dogs receiving alcohol injection. Fibrin or thrombus was present in the diagonal coronary branch in 5 dogs. The conclusion was that the intracoronary injection of 96% ethyl alcohol ablated aconitine-induced ventricular tachycardia effectively. This approach may become a promising new method to treat ventricular tachycardia or other arrhythmia.

Topics: Aconitine; Animals; Coronary Vessels; Dogs; Ethanol; Female; Injections, Intra-Arterial; Male; Myocardium; Necrosis; Tachycardia

The hypothesis whether localized ventricular tachycardia could be ablated by myocardial necrosis induced with chemical agents injected into a coronary artery was tested. In 59 anesthetized dogs, a diagonal branch of the left anterior descending coronary artery was cannulated either occlusively or nonocclusively. Localized ventricular tachycardia was induced by injecting approximately 0.01 ml of 30 micrograms/ml of aconitine solution into the left ventricular wall perfused by the cannulated diagonal branch in 54 dogs. In eight untreated control dogs, aconitine-induced ventricular tachycardia lasted 10.2 +/- 2.3 minutes or degenerated into ventricular fibrillation after 7.0 +/- 4.0 minutes. In the remaining 46 dogs, 1 ml of saline solution, 25, 50 or 100% ethyl alcohol or 0.94 ml (mean [range 0.4 to 2.0]) of 25% phenol at room temperature was injected into the occluded coronary artery and 1 ml of 100% ethyl alcohol at body temperature was injected into the nonoccluded coronary artery. Ventricular tachycardia was eliminated in 9 (82%) of 11 dogs receiving phenol, 7 (88%) of 8 dogs receiving 100% ethyl alcohol occlusively, 6 (75%) of 8 dogs receiving 100% ethyl alcohol nonocclusively and 6 (67%) of 9 dogs receiving 50% ethyl alcohol for an entire follow-up period of 10 to 60 minutes. However, saline solution and 25% ethyl alcohol suppressed ventricular tachycardia only transiently in 8 (53%) of 15 and 3 (60%) of 5 dogs, respectively. Left ventricular end-diastolic pressure rose from 8.0 to 11.2 mm Hg (p less than 0.05) immediately after injection of 100% ethyl alcohol in seven dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aconitine; Animals; Coronary Vessels; Dogs; Electrocardiography; Ethanol; Female; Heart Ventricles; Injections, Intra-Arterial; Male; Myocardium; Necrosis; Phenol; Phenols; Stroke Volume; Tachycardia