Effects of A(1) adenosine receptor agonism using N-6-cyclohexyl-2'-O-methyladenosine in patients with left ventricular dysfunction
Effects of A(1) adenosine receptor agonism using N-6-cyclohexyl-2'-O-methyladenosine in patients with left ventricular dysfunction
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DOI：
10.1161/01.cir.94.6.1212
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发表时间：
1996-09-15
期刊：
影响因子：
37.8
通讯作者：
Pepine, CJ
中科院分区：
文献类型：
--
作者：
Bertolet, BD;Anand, IS;Pepine, CJ
背景应用选择性腺苷A(1)受体激动剂N-6-环己基-2‘-O-甲基腺苷(SDZ-WAG 994)研究腺苷在心力衰竭中的神经调节作用。方法和结果50例有心力衰竭症状和中度左心室收缩功能不全的患者置入气囊漂浮导管。患者接受安慰剂或单次口服1、2或5毫克SDZ-WAG 994。在获得基线测量后，在接下来的4小时内以30分钟的间隔重复血流动力学和电生理记录，然后在接下来的24小时内每6小时重复一次。血液样本中有去甲肾上腺素和肾上腺素。醛固酮、心钠素。分别于给药前和给药后2小时抽血测定血浆肾素活性。A(1)腺苷受体激动剂对全身、右心房、肺动脉或肺毛细血管楔压、心脏指数、呼吸频率、心脏罕见无重要影响。反映A(1)受体介导的活动的PR间期以步进式方式显著增加。在5 mg剂量的SDZ-WAG 994中，心钠素(216+/-137至407+/-146pg/mL)和去甲肾上腺素(477+/-243至618+/-237pg/mL)水平显著升高。结论A(1)腺苷受体激动剂与SDZ-WAG 994联用对这类左心功能不全患者的静息血流动力学无明显影响。PR间期和心钠素水平升高。与腺苷A(1)受体介导的活性一致。此外，还观察到去甲肾上腺素水平的增加，这表明腺苷作为外周神经系统神经调节剂发挥了作用。
Background The role of adenosine as a neuromodulator in heart failure was studied with the use of a selective adenosine A(1) receptor agonist, N-6-cyclohexyl-2'-O-methyladenosine (SDZ-WAG 994).Methods and Results Fifty patients with heart failure symptoms and moderate left ventricular systolic dysfunction had a balloon flotation catheter inserted. Patients received placebo or a single oral dose of either 1, 2, or 5 mg SDZ-WAG 994. After baseline measurements were obtained, hemodynamic and electrophysiological recordings were repeated at 30-minute intervals fur the next 4 hours, then every 6 hours for the next 24 hours. Blood samples for norepinephrine, epinephrine. aldosterone, atrial natriuretic peptide. and plasma renin activity were drawn at baseline and 2 hours after drug administration. A(1) adenosine receptor agonism produced no important effects on systemic, right atrial, pulmonary artery or pulmonary capillary wedge pressures; cardiac index; respiratory rate, ur heart rare. The PR interval reflection of A(1) receptor-mediated activity) increased significantly in a stepwise fashion. At the 5-mg dose of SDZ-WAG 994, significant increases in atrial natriuretic peptide (216+/-137 to 407+/-146 pg/mL) and norepinephrine (477+/-243 to 618+/-237 pg/mL) levels were noted.Conclusions A(1) adenosine receptor agonism with SDZ- WAG 994 resulted in no significant hemodynamic changes at rest in this subset of patients with left ventricular dysfunction. An increase in the PR interval and atrial natriuretic peptide level. consistent with adenosine A(1) receptor-mediated activity, was observed. In addition, an increase in the norepinephrine level was observed, suggesting a role for adenosine as a peripheral nervous system neuromodulator.