Department of Comparative Pathophysiology, Division of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
Toxicol Mech Methods. 2012 Nov;22(9):662-73. doi: 10.3109/15376516.2012.715318. Epub 2012 Aug 30.
This study was conducted to clarify and reevaluate the cardiac and autonomic nervous effects of T-2 toxin, which had been previously examined by several acute experiments, in unrestrained and conscious rats implanted with telemetric transmitters. Two groups of rats were given two subcutaneous injections of 0.1 and 0.5 mg/kg of T-2 toxin with an interval of 3 days. Two other groups of rat were pre-implanted with osmotic minipumps by which atropine (20 mg/kg/day) or propranolol (100 mg/kg/day) was continuously administered preceding subcutaneous injection of T-2 toxin (0.5 mg/kg). The present study demonstrated that T-2 toxin caused marked arrhythmias, such as second-degree atrioventricular (AV) block, sinus bradycardia, supraventricular extrasystole, and ventricular extrasystole, which were accompanied by a significant increase in heart rate and a significant decrease in total power and low- and high-frequency power of heart rate variability, during 3 days of observation after the toxin administration. However, the occurrence of arrhythmia with conduction disturbance such as second-degree atrioventricular blocks was markedly diminished by pretreatment with atropine, while the occurrence of ventricular extrasystole was augmented by atropine. The present study with the telemetric measurement elucidated and confirmed that T-2 toxin produced significant cardiac dysfunctions involving disturbance of the conduction pathway influenced by the autonomic nervous activity and also possible direct effects on cardiac myocytes.
本研究旨在阐明和重新评估 T-2 毒素对心脏和自主神经系统的影响,先前已有多项急性实验对其进行了研究。研究使用植入遥测发射器的不受约束和清醒大鼠进行。两组大鼠分别接受两次皮下注射 0.1 和 0.5mg/kg 的 T-2 毒素,间隔 3 天。另外两组大鼠预先植入渗透微型泵,在皮下注射 T-2 毒素(0.5mg/kg)前,通过微型泵持续给予阿托品(20mg/kg/天)或普萘洛尔(100mg/kg/天)。本研究表明,T-2 毒素在给药后 3 天的观察期间引起明显的心律失常,如二度房室(AV)传导阻滞、窦性心动过缓、室上性期外收缩和室性期外收缩,同时心率显著增加,心率变异性的总功率和低频及高频功率显著降低。然而,阿托品预处理显著减少了伴有二度房室传导阻滞等传导障碍的心律失常的发生,而阿托品则增加了室性期外收缩的发生。本研究通过遥测测量阐明并证实,T-2 毒素产生了显著的心脏功能障碍,涉及自主神经活动影响的传导通路紊乱,以及对心肌细胞的可能直接影响。