Krause K L, Forster H V, Kiner T, Davis S E, Bonis J M, Qian B, Pan L G
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
J Appl Physiol (1985). 2009 Feb;106(2):605-19. doi: 10.1152/japplphysiol.90966.2008. Epub 2008 Dec 18.
Abrupt neurotoxic destruction of >70% of the pre-Bötzinger complex (preBötzC) in awake goats results in respiratory and cardiac failure (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV. J Appl Physiol 97: 1629-1636, 2004). However, in reduced preparations, rhythmic respiratory activity has been found in other areas of the brain stem (Huang Q, St. John WM. J Appl Physiol 64: 1405-1411, 1988; Janczewski WA, Feldman JL. J Physiol 570: 407-420, 2006; Lieske SP, Thoby-Brisson M, Telgkamo P, Ramierz JM. Nature Neurosci 3: 600-607, 2000; St. John WM, Bledsoe TA. J Appl Physiol 59: 684-690, 1985); thus we hypothesized that, when the preBötzC is destroyed incrementally over weeks, time-dependent plasticity within the respiratory network will result in a respiratory rhythm capable of maintaining normal blood gases. Microtubules were bilaterally implanted into the presumed preBötzC of seven goats. After recovery from surgery, studies were completed to establish baseline values for respiratory parameters. At weekly intervals, increasing volumes (in order 0.5, 1, 5, and 10 microl) of ibotenic acid (IA; 50 mM) were then injected into the preBötzC. All IA injections resulted in an acute tachypnea and dysrhythmia featuring augmented breaths, apneas, and increased breath-to-breath variation in breathing. In studies at night, apneas were nearly all central and occurred in the awake state. Breath-to-breath variation in breathing was greater (P < 0.05) during wakefulness than during non-rapid eye movement sleep. However, one week after the final IA injection, the breathing pattern, breath-to-breath variation, and arterial blood gases and pH were unchanged from baseline, but there was a 20% decrease in respiratory frequency (f) and CO(2) sensitivity (P < 0.05), as well as a 40% decrease in the ventilatory response to hypoxia (P < 0.001). In subsequent histological analysis of the presumed preBötzC region of lesioned goats, it was determined that there was a 90 and 92% reduction from control goats in total and neurokinin-1 receptor neurons, respectively. Therefore, it was concluded that 1) the dysrhythmic effects on breathing are state dependent; and 2) after incremental, near total destruction of the presumed preBötzC region, time-dependent plasticity within the respiratory network provides a rhythm capable of sustaining normal arterial blood gases.
清醒山羊中超过70%的前包钦格复合体（preBötzC）突然发生神经毒性破坏会导致呼吸和心脏衰竭（温宁格·J·M、潘·L·G、克鲁姆·L、利克利·T、巴斯塔斯蒂克·J、霍奇斯·M·R、费罗阿·T·R、戴维斯·S、福斯特·H·V。《应用生理学杂志》97: 1629 - 1636，2004年）。然而，在简化的实验准备中，已在脑干的其他区域发现了节律性呼吸活动（黄·Q、圣约翰·W·M。《应用生理学杂志》64: 1405 - 1411，1988年；扬采夫斯基·W·A、费尔德曼·J·L。《生理学杂志》570: 407 - 420，2006年；利斯克·S·P、托比 - 布里松·M、特尔加莫·P、拉米雷斯·J·M。《自然神经科学》3: 600 - 607，2000年；圣约翰·W·M、布莱索·T·A。《应用生理学杂志》59: 684 - 690，1985年）；因此我们推测，当preBötzC在数周内逐渐被破坏时，呼吸网络内的时间依赖性可塑性将产生一种能够维持正常血气的呼吸节律。将微管双侧植入七只山羊的假定preBötzC中。手术后恢复后，完成各项研究以确定呼吸参数的基线值。然后每周一次，将递增体积（依次为0.5微升、1微升、5微升和10微升）的鹅膏蕈氨酸（IA；50毫摩尔）注入preBötzC。所有IA注射均导致急性呼吸急促和心律失常，其特征为呼吸增强、呼吸暂停以及呼吸间变异性增加。在夜间研究中，呼吸暂停几乎全部为中枢性的，且发生在清醒状态。呼吸间变异性在清醒时比在非快速眼动睡眠时更大（P < 0.05）。然而，在最后一次IA注射一周后，呼吸模式、呼吸间变异性以及动脉血气和pH与基线相比无变化，但呼吸频率（f）和二氧化碳敏感性降低了20%（P < 0.05），以及对低氧的通气反应降低了40%（P < 0.001）。在对受损山羊假定preBötzC区域的后续组织学分析中，确定与对照山羊相比，该区域的总数和神经激肽 - 1受体神经元分别减少了90%和92%。因此，得出以下结论：1）对呼吸的心律失常作用具有状态依赖性；2）在假定的preBötzC区域逐渐接近完全破坏后，呼吸网络内的时间依赖性可塑性提供了一种能够维持正常动脉血气的节律。
