Nejman G D, Griffith R, Van Ligten P, Hoekstra J, Casto L, Miller D D, Brown C G
Division of Emergency Medicine, Ohio State University, Columbus 43210.
Resuscitation. 1990 Dec;20(3):243-52. doi: 10.1016/0300-9572(90)90007-2.
We hypothesized that substitution of the hydroxyl group (OH) on the beta carbon of norepinephrine (NE) with an amino group would yield a compound, 1-(3,4-dihydroxyphenyl)-1,2-diaminoethane (DHPDAE), that would maintain the hemodynamic properties of NE during CPR, but would decrease the rate of post-defibrillation dysrhythmias. Six mixed breed swine weighing greater than 28 kg were studied. The animals were instrumented for cerebral (CBF) and myocardial blood flow (MBF) measurements. Ventricular fibrillation (VF) was induced. After 10 min of VF, CPR was begun. After 3 min of CPR, 2.5 mg/kg of DHPDAE was administered and CPR continued. Defibrillation was attempted 3.5 min after drug administration. CBF, MBF and defibrillation rates were compared to an historical control group receiving 0.16 mg/kg of NE. Outcome variables were compared using a Wilcoxon Rank Sum test and Fisher-exact test. NE significantly improved CBF and MBF compared to DHPDAE. All the animals in the NE group were successfully defibrillated into a perfusing rhythm. Sixty percent of the NE treated animals experienced post-defibrillation ventricular dysrhythmias. None of the animals in the DHPDAE were successfully defibrillated into a perfusing rhythm. Substitution of the hydroxyl group on the beta-carbon of NE with an amino group significantly decreases the hemodynamic properties of the parent molecule.
我们推测，用氨基取代去甲肾上腺素（NE）β碳上的羟基（OH）会产生一种化合物，即1-(3,4-二羟基苯基)-1,2-二氨基乙烷（DHPDAE），它在心肺复苏期间能维持NE的血流动力学特性，但会降低除颤后心律失常的发生率。研究了6只体重超过28 kg的杂种猪。对这些动物进行了脑血流（CBF）和心肌血流（MBF）测量的仪器植入。诱发心室颤动（VF）。VF持续10分钟后开始心肺复苏。心肺复苏3分钟后，给予2.5 mg/kg的DHPDAE并继续进行心肺复苏。给药3.5分钟后尝试除颤。将CBF、MBF和除颤率与接受0.16 mg/kg NE的历史对照组进行比较。使用Wilcoxon秩和检验和Fisher精确检验比较结果变量。与DHPDAE相比，NE显著改善了CBF和MBF。NE组的所有动物均成功除颤并恢复灌注心律。接受NE治疗的动物中有60%出现除颤后室性心律失常。DHPDAE组的动物均未成功除颤并恢复灌注心律。用氨基取代NE的β碳上的羟基会显著降低母体分子的血流动力学特性。
