MECHANISMS OF CANINE GASTRIC DYSRHYTHMIA
MECHANISMS OF CANINE GASTRIC DYSRHYTHMIA
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DOI：
10.1016/0016-5085(87)90975-9
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发表时间：
1987-04-01
期刊：
影响因子：
29.4
通讯作者：
MALAGELADA, JR
中科院分区：
文献类型：
--
作者：
KIM, CH;ZINSMEISTER, AR;MALAGELADA, JR
我们推测当外源性激活时，局部合成和释放的胰高血糖素可能是引发胃节律障碍的旁分泌途径。研究分为三个部分。在第1部分中，在7只犬中进行了剂量反应研究，以估计已知可引起胃节律障碍的4种药物的95%有效剂量。在第2部分中，我们确定了三种假定的阻滞剂在预防胃节律障碍的药物诱导方面的相对疗效。在第3部分中，进行了几个辅助实验。结果表明，肾上腺素、甲硫氨酸脑啡肽、前列腺素E2和胰高血糖素的动脉内推注各自诱导胃节律障碍的发作，而盐水注射没有。这些心律失常药物的95%有效剂量分别为10.5、77.0、35.0和407.0 μ g/kg。肾上腺素的节律紊乱作用可被酚妥拉明和吲哚美辛阻断，但不被纳洛酮阻断。甲硫脑啡肽的节律紊乱作用可被纳洛酮和吲哚美辛阻断，但不能被酚妥拉明阻断。胰高血糖素的节律紊乱作用不被酚妥拉明、纳洛酮或吲哚美辛阻断。吲哚美辛对肾上腺素诱导的胃节律紊乱的抑制作用与甲氨蝶呤相同。因此，我们得出结论，当地的肾上腺素介导的生产胃节律紊乱的肾上腺素和甲硫氨酸脑啡肽，然而，胰高血糖素引起胃节律紊乱的非前列腺素介导的机制。
We postulated that local synthesis and release of prostaglandins might be the paracrine pathway that triggers gastric dysrhythmia when exogenously activated. The study was divided into three parts. In part 1, a dose-response study was performed in 7 dogs to estimate the 95% effective dose for four pharmacologic agents known to cause gastric dysrhythmia. In part 2, we determined the relative efficacy of three putative blockers in preventing pharmacologic induction of gastric dysrhythmia. In part 3, several ancillary experiments were performed. The results show that an intraarterial bolus of epinephrine, met-enkephalin, prostaglandin E2, and glucagon each induced episodes of gastric dysrhythmia, whereas saline injections did not. The 95% effective dose of these dysrhythmic drugs were 10.5, 77.0, 35.0, and 407.0 .mu.g/kg, respectively. The dysrhythmic action of epinephrine was blocked by phentolamine and indomethacin but not by naloxone. The dysrhythmic action of met-enkephalin was blocked by naloxone and indomethacin but not by phentolamine. The dysrhythmic action of glucagon was not blocked by phentolamine, naloxone, or indomethacin. The inhibitory effect of indomethacin on epinephrine-induced gastric dysrhythmia was shared by meclofenamate. Thus, we conclude that local prostaglandins mediate the production of gastric dysrhythmias by epinephrine and met-enkephalin; however, glucagon causes gastric dysrhythmias by a non-prostaglandin-mediated mechanism.