Preliminary evidence for the mechanism underlying the development of tolerance to prazosin in congestive heart failure: the alpha-agonistic properties of dobutamine unmasked by prazosin treatment.
Preliminary evidence for the mechanism underlying the development of tolerance to prazosin in congestive heart failure: the alpha-agonistic properties of dobutamine unmasked by prazosin treatment.
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充血性心力衰竭中哌唑嗪耐受性发展机制的初步证据：哌唑嗪治疗揭示的多巴酚丁胺的α激动特性。
DOI：
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发表时间：
1993
影响因子：
3
通讯作者：
G. Giesen
中科院分区：
文献类型：
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作者：
F. Kersting;M. Kupp;G. Giesen
对纽约心脏协会(NYHA)III-IV级慢性心力衰竭患者应用不同血管扩张剂的急性和慢性治疗的血流动力学效应进行了评估。将24名患者随机分为四组，每组6名：硝酸异山梨酯、双氢呋喃、卡托普利或哌唑嗪。此外，我们通过增加2.5、5.0和10.0微克/公斤/分钟的输注速度来评估多巴酚丁胺对血液动力学的反应，在用任何一种血管扩张剂进行为期3个月的慢性治疗的开始和结束时。在血管扩张治疗开始时，多巴酚丁胺引起心脏指数的剂量依赖性增加和平均肺动脉压(PAP)的下降，并在用硝酸异山梨酯、双氢呋喃或卡托普利进行为期3个月的慢性治疗期间保持这种效果。但经6 mg/d的哌唑嗪治疗3个月后，平均PAP升高至治疗前水平以上，多巴酚丁胺引起PAP进一步升高，从而逆转了最初的作用。多巴酚丁胺引起的心脏指数增加几乎没有变化。我们得出结论，哌唑嗪慢性治疗后对PAP的影响逆转可能至少部分是由于α1-肾上腺素受体上调所致。这似乎被外消旋多巴酚丁胺混合物的(-)对映体的α1肾上腺素能受体激动剂所掩盖。
The hemodynamic effects of acute and chronic treatment with different vasodilators were assessed in patients with chronic heart failure of New York Heart Association (NYHA) class III-IV. Each of 24 patients was randomly allocated; 6 to each of four groups: isosorbide dinitrate, dihydralazine, captopril, or prazosin. In addition, we evaluated the hemodynamic response to dobutamine by using increasing infusion rates of 2.5, 5.0, and 10.0 micrograms/kg/min at the start and end of a 3-month period of chronic therapy with either vasodilator. Dobutamine caused a dose-dependent increase in cardiac index and a decrease in mean pulmonary artery pressure (PAP) at the start of the vasodilatory treatment and maintained the effects during a 3-month period of chronic treatment with either isosorbide dinitrate, dihydralazine, or captopril. After 3-month therapy with 6 mg/day prazosin, however, mean PAP was increased above pretreatment value and dobutamine caused a further increase in PAP, thus reversing the initial effects. The dobutamine-induced increase in cardiac index remained virtually unchanged. We conclude that the reversal of the effects on PAP after chronic treatment with prazosin may be, at least in part, due to upregulation of alpha 1-adrenoceptors. This appears to be unmasked by the alpha 1-adrenoceptor agonist of the (-)-enantiomer of the racemic mixture of (+/-)-dobutamine.