Newton001 Temporal profiling of cardiac autonomic changes following organophosphorus poisoning

有机磷化合物是巴西、埃及、印度和美国等许多国家使用最广泛的杀虫剂。根据最新报告，OP是巴西大部分中毒、死亡和自杀未遂事件的罪魁祸首。最新的巴西国家毒物药物中毒报告系统（SINITOX，2009年）表明，2001年至2007年，仅在一个州（圣埃斯皮里托），农药中毒人数就比前几年同期增加了347%。在巴西东南部地区，这个州的有机磷中毒病例数（5，512例）位居第二。OP化合物通过阻断一种酶（乙酰胆碱酯酶）干扰神经细胞通讯而起作用。这导致中枢和外周神经系统的破坏。OP对心脏、循环和呼吸的影响可能是其致死性的主要原因。虽然OP中毒的临床症状得到了很好的描述，但我们对确切机制及其时间过程的理解非常有限，这是我们希望研究的。这一点很重要，因为它将揭示相对于OP中毒后的时间最有效的治疗方法。OP暴露后，临床症状分为3个阶段：（i）最初几小时内的急性危象综合征;（ii）12-96小时之间的中间阶段和（iii）迟发性神经系统功能障碍阶段。我们希望了解在OP中毒的前两个阶段，心脏、循环和呼吸系统症状是如何发生的，以及这些症状是否在先前存在的心力衰竭的情况下恶化。我们认为，OP中毒的有害影响会立即影响控制心脏、循环和呼吸的外周神经系统，随着时间的推移而恶化，如果受试者预先存在心力衰竭，则会被夸大。

Organophosphorus (OP) compounds are the most widely used insecticides in many countries including Brazil, Egypt, India and USA. According to the latest reports, OP are responsible for the majority of poisonings, deaths and suicides attempts in Brazil. The latest Brazilian National System reporting on Toxico-Pharmacological Poisoning (SINITOX, 2009) indicated that the number of people poisoned by pesticides between 2001 and 2007 increased in 347% in a single State alone (Espirito Santo) compared to an equivalent period in previous years. This Brazilian State now has the second highest number of OP poisoning cases (5,512) within the south-east region of Brazil. OP compounds act by interfering with nerve cell communication by blocking an enzyme (acetyl cholinesterase). This leads to disruption of both the central and peripheral nervous systems. The effects on the heart, circulation and breathing by OP are likely to contribute in a major way to their lethality. Although clinical signs of OP poisoning are well described, our understanding of the precise mechanisms and their time course is highly limited and it this we wish to study. This is important because it would reveal the most effective therapeutic treatment relative to the time after OP poisoning. Following OP exposure, clinical symptoms are classified into 3 stages: (i) acute crisis syndrome within the first few hours; (ii) an intermediate stage between 12-96 hours and (iii) a delayed nervous system dysfunction stage. We wish to understand how the heart, circulation and respiratory symptoms occur within the first two stages of OP poisoning, and whether these are worsened in conditions of pre-existing heart failure. We propose that the deleterious effects of OP poisoning immediately affect the peripheral nervous system controlling the heart, circulation and respiration, worsen with time and are exaggerated if the subject has pre-existing heart failure.