Chang F C, Benton B J, Lenz R A, Capacio B R
Pathophysiology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Toxicon. 1993 May;31(5):645-64. doi: 10.1016/0041-0101(93)90119-4.
Effects of saxitoxin (STX; 10 micrograms/kg; i.p.) on cardio-respiratory activities were evaluated in urethane-anesthetized guinea-pigs. Concurrent recordings were made of electrocorticogram (ECoG), bulbar respiratory-related unit activities, diaphragmatic electromyogram (DEMG), electrocardiogram (Lead II ECG), blood pressure, heart rate, end-tidal CO2, arterial O2/CO2 tensions, and arterial pH. The average time to STX-induced respiratory failure was about 10 min. The most striking effect prior to apnea was a state of progressive bradypnea which emerged 5-7 min after the toxin administration. Other noteworthy responses included (i) a time-dependent decrease in ECoG amplitudes which typically began before the development of a bradypneic profile; (ii) an increasing degree of diaphragm neuromuscular blockade; (iii) a state of combined hypercapnia and uncompensated acidemia; (iv) a declining blood pressure; (v) an incrementally dysfunctional myocardial performance; and (vi) an increasingly degenerative central respiratory activity profile which ultimately culminated in a complete loss of central respiratory drive. The therapeutic effect of intratracheally administered oxygen was equivocal in that the cardio-respiratory activities, be they of central of peripheral nature, remained conspicuously dysfunctional and precarious despite 100% oxygen ventilation. What can be inferred from this study is two-fold. First, STX-induced ventilatory insufficiency can be attributed to a loss of functional integrity of both central and peripheral respiratory system components. That is, although diaphragm blockade contributes significantly to STX-induced respiratory failure, analyses of single respiratory unit activity data revealed that the central respiratory rhythmogenic mechanism also appeared to play a pivotal role in the development of a bradypneic profile which promotes, and directly causes, a complete loss of respiratory drive. Second, a state of unabating depression of central respiratory activities, which seemed to be refractory to the effect of O2, suggests STX has a direct and persistent action on medullary rhythmogenic mechanisms. In conclusion, these findings indicate that both central and peripheral cardio-respiratory components are critically involved in STX-induced apnea, dysfunctional cardiovascular performance, and lethality.
在氨基甲酸乙酯麻醉的豚鼠中评估了石房蛤毒素（STX；10微克/千克；腹腔注射）对心肺活动的影响。同时记录了皮质电图（ECoG）、延髓呼吸相关单位活动、膈肌肌电图（DEMG）、心电图（导联II ECG）、血压、心率、呼气末二氧化碳、动脉血氧/二氧化碳张力以及动脉pH值。STX诱导呼吸衰竭的平均时间约为10分钟。呼吸暂停前最显著的影响是进行性呼吸过缓状态，在毒素给药后5 - 7分钟出现。其他值得注意的反应包括：（i）ECoG振幅随时间下降，通常在呼吸过缓状态出现之前就开始；（ii）膈肌神经肌肉阻滞程度增加；（iii）合并高碳酸血症和未代偿性酸血症状态；（iv）血压下降；（v）心肌功能逐渐失调；（vi）中枢呼吸活动逐渐退化，最终导致中枢呼吸驱动完全丧失。气管内给予氧气的治疗效果不明确，因为尽管进行了100%的氧气通气，心肺活动，无论是中枢性还是外周性的，仍然明显功能失调且不稳定。从这项研究中可以推断出两点。首先，STX诱导的通气不足可归因于中枢和外周呼吸系统组成部分功能完整性的丧失。也就是说，尽管膈肌阻滞对STX诱导的呼吸衰竭有显著贡献，但对单个呼吸单位活动数据的分析表明，中枢呼吸节律产生机制在促进并直接导致呼吸驱动完全丧失的呼吸过缓状态的发展中似乎也起关键作用。其次，中枢呼吸活动持续抑制的状态似乎对氧气的作用有抗性，这表明STX对延髓节律产生机制有直接和持续的作用。总之，这些发现表明中枢和外周心肺组成部分都严重参与了STX诱导的呼吸暂停、心血管功能失调和致死性。
