简介:使用选择性的体内研究,局部阿片类药物拮抗剂注射或局部阿片类药物受体缺失已经确定,全身性阿片类药物通过多个呼吸相关脑干区域的效应,剂量依赖性地抑制呼吸输出量.方法:经ZablockiVA医学中心动物研究小组委员会批准,实验在53个去脊椎动物中进行,迷走神经切断术,等中毒高氧时,任一性别的机械通气犬。我们在Pontine呼吸组(PRG,n=432)和preBötzinger/Bötzinger复杂区域(preBötC/BötC,n=213)在静脉输注瑞芬太尼(0.1-1mcg/kg/min)之前和期间,然后直到完全恢复the神经活动。使用广义线性混合模型来确定瑞芬太尼引起的Fn变化以及瑞芬太尼引起的Fn变化与吸气和呼气持续时间变化以及峰值膈活动之间的统计关联。通过对动物的随机效应控制分析,run,和神经元类型。结果:瑞芬太尼降低了前BötC/BötC以及吸气(I)中大多数神经元亚型的Fn,吸气-呼气,PRG中的呼气(E)衰减和非呼吸调节神经元。PRG吸气和非呼吸调节的神经元活动的减少与吸气持续时间的增加有关。在preBötC,随着吸气持续时间的增加,I-递减神经元活性的降低与呼气和E-递减活性的增加相关.相比之下,I增强神经元活动的减少与吸气持续时间的减少有关。讨论:虽然统计关联不一定意味着因果关系,我们的数据提示了阿片样物质引起的PRG和preBötC/BötC呼气持续时间增加的机制,以及高剂量阿片样物质引起的吸气衰竭可能是由于preBötC/BötC吸气前神经元的活性降低和吸气前斜坡样活动的斜率降低以及preBötC/BötCI增强神经元的抑制引起的.其他研究必须阐明观察到的神经元活动变化是否是由于直接的神经元抑制或减少的兴奋性输入。
Introduction: In vivo studies using selective, localized opioid antagonist injections or localized opioid receptor deletion have identified that systemic opioids dose-dependently depress respiratory output through effects in multiple respiratory-related brainstem areas. Methods: With approval of the subcommittee on animal studies of the Zablocki VA Medical Center, experiments were performed in 53 decerebrate, vagotomized, mechanically ventilated dogs of either sex during isocapnic hyperoxia. We performed single neuron recordings in the Pontine Respiratory Group (PRG, n = 432) and preBötzinger/Bötzinger complex region (preBötC/BötC, n = 213) before and during intravenous remifentanil infusion (0.1-1 mcg/kg/min) and then until complete recovery of phrenic nerve activity. A generalized linear mixed model was used to determine changes in Fn with remifentanil and the statistical association between remifentanil-induced changes in Fn and changes in inspiratory and expiratory duration and peak phrenic activity. Analysis was controlled via random effects for animal, run, and neuron type. Results: Remifentanil decreased Fn in most neuron subtypes in the preBötC/BötC as well as in inspiratory (I), inspiratory-expiratory, expiratory (E) decrementing and non-respiratory modulated neurons in the PRG. The decrease in PRG inspiratory and non-respiratory modulated neuronal activity was associated with an increase in inspiratory duration. In the preBötC, the decrease in I-decrementing neuron activity was associated with an increase in expiratory and of E-decrementing activity with an increase in inspiratory duration. In contrast, decreased activity of I-augmenting neurons was associated with a decrease in inspiratory duration. Discussion: While statistical associations do not necessarily imply a causal relationship, our data suggest mechanisms for the opioid-induced increase in expiratory duration in the PRG and preBötC/BötC and how inspiratory failure at high opioid doses may result from a decrease in activity and decrease in slope of the pre-inspiratory ramp-like activity in preBötC/BötC pre-inspiratory neurons combined with a depression of preBötC/BötC I-augmenting neurons. Additional studies must clarify whether the observed changes in neuronal activity are due to direct neuronal inhibition or decreased excitatory inputs.