Effects of aminophylline, isoproterenol, and neostigmine on hypercapnic depression of diaphragmatic contractility.
Effects of aminophylline, isoproterenol, and neostigmine on hypercapnic depression of diaphragmatic contractility.
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氨茶碱、异丙肾上腺素和新斯的明对膈肌收缩力高碳酸血症抑制的影响。
DOI：
10.1164/arrd.1985.132.2.241
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Roussos,C
中科院分区：
文献类型：
--
作者：
Howell,S;Fitzgerald,RS;Roussos,C
我们研究了氨茶碱、异丙肾上腺素和新斯的明对高碳酸血症引起的膈肌收缩力下降的影响。胸腔打开，动物接受机械通气，腹部周围石膏石膏，保持隔膜的长度和几何形状不变。通过分析不同频率上膈肌刺激产生的经膈压力（Pdi）来评估收缩性。行双侧膈切除术以防止膈肌自发运动。高碳酸血症（PaCO2, 85 mmHg）在低频率和高频率刺激下使Pdi降低10%。随后，在每个刺激频率下，氨茶碱（20 mg/kg）使Pdi恢复到对照值（p < 0.05），而新斯的明（0.25和1.0 mg）仅在低频率下恢复Pdi （p < 0.05）。异丙肾上腺素在任何频率下都不能改善Pdi。抽搐特征分析显示，高碳酸血症使抽搐峰值幅度降低了17%，这是Pdi下降的根本原因。所有3种药物的低剂量和高剂量显著逆转了这一作用，将峰值抽搐张力提高到等于或大于对照组的值（p < 0.05）。此外，氨茶碱（40 mg/kg）和新斯的明（0.25和1.0 mg）显著延长了抽搐达到峰值张力的时间（p < 0.05），异丙肾上腺素（5和20µg/min）显著缩短了抽搐半松弛时间（p < 0.05）。我们得出的结论是，氨茶碱和新斯的明通过增强抽搐幅度来改善高血氧症期间膈肌的收缩力，而异丙肾上腺素不会增加收缩力，因为抽搐持续时间减少的过程掩盖了抽搐幅度改善的效果。
We investigated the effects of aminophylline, isoproterenol, and neostigmine on decreased diaphragmatic contractility induced by hypercapnia. With the thorax open, the animal receiving mechanical ventilation, and a plaster cast around the abdomen, constant length and geometry of the diaphragm were maintained. Contractility was assessed by analysis of transdiaphragmatic pressure (Pdi) generated during supramaximal phrenic stimulation at different frequencies. Bilateral phrenectomy was performed to prevent spontaneous diaphragm movement. Hypercapnia (PaCO2, 85 mmHg) reduced Pdi by 10% at low and high frequencies of stimulation. Subsequently, aminophylline (20 mg/kg) restored Pdi to the control value at every frequency of stimulation (p < 0.05), whereas neostigmine (0.25 and 1.0 mg) restored Pdi at low frequencies only (p < 0.05). Isoproterenol did not improve Pdi at any frequency. Analysis of twitch characteristics revealed that hypercapnia reduced peak twitch amplitude by 17%, this being the underlying cause of the decrease in Pdi. Low and high doses of all 3 drugs significantly reversed this effect by improving peak twitch tension to values equal with or greater than control values (p < 0.05). In addition, aminophylline (40 mg/kg) and neostigmine (0.25 and 1.0 mg) significantly increased time to peak tension of the twitch (p < 0.05) and isoproterenol (5 and 20 µg/min) significantly decreased twitch half relaxation time (p < 0.05). We conclude that aminophylline and neostigmine improve diaphragmatic contractility during hypercapnia by virtue of their potentiating effect on twitch amplitude, whereas isoproterenol does not increase contractility because the process underlying the decrease in twitch duration masks the effect of an improved twitch amplitude.