Lee H R, Hershberger R E, Port J D, Rasmussen R, Renlund D G, O'Connell J B, Gilbert E M, Mealey P C, Volkman K, Menlove R
Cardiology Division, University of Utah School of Medicine, Salt Lake City.
J Thorac Cardiovasc Surg. 1991 Aug;102(2):246-58.
During a 3-year period we administered enoximone, a phosphodiesterase inhibitor with positive inotropic and vasodilator properties, to 73 pretransplantation patients with end-stage heart failure who exhibited a clinical requirement for additional inotropic support. The clinical course and myocardial beta-adrenergic receptor status in the explanted hearts of these 73 patients was compared with results in 113 concurrently listed pretransplantation patients not requiring additional inotropic support. Only three patients required cessation of enoximone because of adverse effects, all from exacerbation of ventricular arrhythmias. Sixty-six of 73 (90.4%) enoximone-treated patients ultimately underwent cardiac transplantation a mean of 39.2 +/- 6.6 days (range 1 to 221 days) after starting enoximone, whereas seven patients (9.6%) died awaiting cardiac transplantation. The respective 1-, 3-, and 6-month pretransplantation survival rates of patients treated with enoximone calculated from their time on the waiting list for transplantation were 88.0%, 82.5%, and 82.5% compared with 92.1%, 83.8%, and 76.2% in control patients not receiving enoximone (all p = not significant). In 25 patients who received enoximone, ventricular myocardial beta-adrenergic receptors were measured at the time of transplantation and compared with values in failing ventricles from 52 pretransplantation patients not exposed to enoximone. Compared with ventricular myocardium of patients not given enoximone or intravenous beta-adrenergic agonists, total beta-adrenergic receptor (beta 1 plus beta 2) density was not decreased in patients treated with enoximone or enoximone plus intravenous beta-adrenergic agonists, but was decreased by 31% (p less than 0.05) in patients given intravenous beta-adrenergic agonists alone. Additionally, patients treated with enoximone had higher myocardial beta 2-adrenergic receptor densities than respective subgroups treated without (28% higher, p less than 0.01) or with (65% higher, p less than 0.01) intravenous beta-adrenergic agonists. Finally, isoproterenol- or calcium-mediated contractile responses in isolated right ventricular preparations from 14 patients treated with enoximone were similar to values in control patients not exposed to enoximone or intravenous beta-adrenergic agonists, suggesting that enoximone-related beta-adrenergic subsensitivity or damage to the contractile apparatus does not occur.
在3年期间，我们对73例终末期心力衰竭的移植前患者使用了依诺昔酮，这是一种具有正性肌力和血管舒张特性的磷酸二酯酶抑制剂，这些患者临床上需要额外的正性肌力支持。将这73例患者移植心脏的临床病程和心肌β-肾上腺素能受体状态与113例同时登记的不需要额外正性肌力支持的移植前患者的结果进行了比较。只有3例患者因不良反应需要停用依诺昔酮，均因室性心律失常加重。73例接受依诺昔酮治疗的患者中有66例（90.4%）最终接受了心脏移植，开始使用依诺昔酮后平均39.2±6.6天（范围1至221天），而7例患者（9.6%）在等待心脏移植期间死亡。从等待移植名单上的时间计算，接受依诺昔酮治疗的患者移植前1个月、3个月和6个月的生存率分别为88.0%、82.5%和82.5%，而未接受依诺昔酮的对照患者为92.1%、83.8%和76.2%（所有p值均无统计学意义）。在25例接受依诺昔酮治疗的患者中，在移植时测量了心室心肌β-肾上腺素能受体，并与52例未接触依诺昔酮的移植前患者衰竭心室中的值进行了比较。与未给予依诺昔酮或静脉注射β-肾上腺素能激动剂的患者的心室心肌相比，接受依诺昔酮或依诺昔酮加静脉注射β-肾上腺素能激动剂治疗的患者的总β-肾上腺素能受体（β1加β2）密度没有降低，但单独给予静脉注射β-肾上腺素能激动剂的患者降低了31%（p<0.05）。此外，接受依诺昔酮治疗的患者的心肌β2-肾上腺素能受体密度高于未接受（高28%，p<0.01）或接受（高65%，p<0.01）静脉注射β-肾上腺素能激动剂的相应亚组。最后，14例接受依诺昔酮治疗的患者的离体右心室制剂中异丙肾上腺素或钙介导的收缩反应与未接触依诺昔酮或静脉注射β-肾上腺素能激动剂的对照患者的值相似，这表明与依诺昔酮相关的β-肾上腺素能亚敏感性或对收缩装置的损害并未发生。
