The use of hypercapnic conditions to assess opioid-induced respiratory depression in rats.
The use of hypercapnic conditions to assess opioid-induced respiratory depression in rats.
复制标题
使用高碳酸血症条件评估阿片类药物引起的大鼠呼吸抑制。
DOI：
10.1016/j.vascn.2021.107101
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发表时间：
2021-09
影响因子：
1.9
通讯作者：
Hiranita T
中科院分区：
文献类型：
--
作者：
Crowley ML;Restrepo LF;Gamez-Jimenez LR;Patel A;Braun T;Pallares VLC;Ho NP;Reeves ME;McCurdy CR;McMahon LR;Hiranita T
全身体积描记法（WBP）是一种评估阿片类药物呼吸抑制作用的临床前方法，阿片类药物是人类阿片类药物过量死亡的主要原因。然而，在正常碳酸条件下的低基线呼吸速率（即，“地板”效应）可使得呼吸减少的测量具有挑战性。我们评估了高碳酸血症诱导的呼吸增加作为评估阿片类药物诱导的大鼠呼吸减少的策略。WBP用于评估大鼠在光周期的昼夜期间在正常碳酸和高碳酸（8%CO2）条件下的呼吸频率、潮气量和分钟通气量。μ阿片受体激动剂芬太尼静脉给药，热板试验用于评估急性镇痛作用。高碳酸血症诱导的呼吸参数（频率、每分钟通气量和潮气量）增加在正常碳酸血症条件下不降低相同参数的剂量下被芬太尼降低。这些发现表明，与活动和呼吸频率通常较低的大鼠昼夜期间的评估相比，高碳酸血症增加了对芬太尼呼吸抑制效应的敏感性，即，存在地板效应。目前的方法对阿片类药物诱导的呼吸抑制高度敏感，因此为临床前环境中的评估提供了一种有用的方法。
Whole-body plethysmography (WBP) in unrestrained, non-anesthetized rodents is a preclinical method to assess the respiratory depressant effects of opioids, the leading cause of opioid overdose death in humans. However, low baseline respiration rates under normocapnic conditions (i.e., “floor” effect) can render the measurement of respiratory decreases challenging. We assessed hypercapnia-induced increases in respiration as a strategy to assess opioid-induced decreases in respiration in rats. WBP was used to assess respiration frequency, tidal volume and minute volume in the presence of normocapnic and hypercapnic (8% CO2) conditions in rats during the rat diurnal period of the light cycle. The mu-opioid receptor agonist fentanyl was administered intravenously, and the hot plate test was used to assess acute antinociception. Hypercapnia-induced increases in respiratory parameters (frequency, minute volume, and tidal volume) were decreased by fentanyl at doses that did not decrease the same parameters under the normocapnic conditions. These findings show that hypercapnia increases sensitivity to respiratory depressant effects of fentanyl, as compared with assessments during the rat diurnal period when activity and breathing rate are generally low, i.e., there is a floor effect. The current approach is highly sensitive to opioid-induced respiratory depression, and therefore provides a useful method for assessment in a pre-clinical setting.
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影响因子：
3.6
作者：
Bessiere, Baptiste;Laboureyras, Emilie;Simonnet, Guy
通讯作者：
Simonnet, Guy
影响因子：
3.8
作者：
Goineau, Sonia;Rompion, Sonia;Picard, Sandra
通讯作者：
Picard, Sandra
影响因子：
2.3
作者：
Lonergan, T;Goodchild, AK;Pilowsky, PM
通讯作者：
Pilowsky, PM
DOI：
10.1016/j.vascn.2011.10.001
发表时间：
2012-01-01
影响因子：
1.9
作者：
Nirogi, Ramakrishna;Shanmuganathan, Dhanalakshmi;Kancharla, Baburao
通讯作者：
Kancharla, Baburao
影响因子：
5.1
作者：
Chear NJ;León F;Sharma A;Kanumuri SRR;Zwolinski G;Abboud KA;Singh D;Restrepo LF;Patel A;Hiranita T;Ramanathan S;Hampson AJ;McMahon LR;McCurdy CR
通讯作者：
McCurdy CR