Role of the renin-angiotensin system in the development of hemodynamic and clinical tolerance to long-term prazosin therapy in patients with severe chronic heart failure.
Role of the renin-angiotensin system in the development of hemodynamic and clinical tolerance to long-term prazosin therapy in patients with severe chronic heart failure.
复制标题
肾素-血管紧张素系统在严重慢性心力衰竭患者血流动力学和长期哌唑嗪治疗临床耐受性发展中的作用。
DOI：
10.1016/s0735-1097(86)80479-x
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发表时间：
1986
影响因子：
24
通讯作者：
Yushak,M
中科院分区：
文献类型：
--
作者：
Packer,M;Medina,N;Yushak,M
27例严重慢性心力衰竭患者在接受哌唑嗪长期治疗前和治疗期间进行右心导管检查，这些患者在3至12周的药物治疗期间进行了一系列血流动力学研究。地高辛和呋塞米的剂量在试验期间保持恒定;此外，27名患者中的11名被分配接受螺内酯的伴随治疗，而其余16名患者没有接受醛固酮拮抗剂。哌唑嗪的第一剂量产生心脏指数的显著增加和平均动脉压的显著降低，两组患者的左心室充盈压和全身血管阻力（所有p < 0.01），但在48小时后，两组中这些作用迅速减弱（p < 0.01），并在长期治疗期间保持减弱。3 ~ 12周后，心脏指数恢复到治疗前水平，停药后没有降低;平均动脉压、左心室充盈压和全身血管阻力在3 ~ 12周后仍显著降低（尽管减弱）（p < 0.01），停药后恢复到治疗前水平。这些反应的幅度和时间过程没有改变与螺内酯合并治疗。血流动力学疗效完全丧失在24例接受长期血流动力学研究的患者中，14例（58%）观察到哌唑嗪耐受性，且未伴随血浆肾素活性或体重的长期变化，这些数据表明，哌唑嗪仅在30 - 40%的患者中产生长期血流动力学和临床益处严重慢性心力衰竭患者中，并且不支持肾素-血管紧张素系统在对α-肾上腺素能阻滞剂耐受性发展中的作用。这种低应答率解释了为什么大多数哌唑嗪治疗心力衰竭的随机双盲试验未能证明安慰剂治疗患者与活性药物治疗患者之间存在显著差异。
Right heart catheterization was performed before and during long-term therapy with prazosin in 27 patients with severe chronic heart failure who underwent serial hemodynamic studies during 3 to 12 weeks of treatment with the drug. Doses of digoxin and furosemide remained constant during the trial; in addition, 11 of the 27 patients were assigned to concomitant therapy with spironolactone, while the remaining 16 patients did not receive the aldosterone antagonist.First doses of prazosin produced marked increases in cardiac index and marked decreases in mean arterial pressure, left ventricular filling pressure and systemic vascular resistance in both groups of patients (all p < 0.01), but these effects became rapidly attenuated (p < 0.01) in both groups after 48 hours and remained attenuated during long-term therapy. After 3 to 12 weeks, values for cardiac index returned to pretreatment levels and did not decrease when the drug was withdrawn; values for mean arterial pressure, left ventricular filling pressure and systemic vascular resistance remained significantly decreased (although attenuated) after 3 to 12 weeks (p < 0.01) and increased to pretreatment values when the drug was withdrawn. The magnitude and time course of these responses were not altered by concomitant therapy with spironolactone. Complete loss of hemodynamic efficacy (prazosin tolerance) was noted in 14 (58%) of the 24 patients who underwent long-term hemodynamic study and was not accompanied by longterm changes in plasma renin activity or body weight.These data indicate that prazosin produces long-term hemodynamic and clinical benefits in only 30 to 40% of patients with severe chronic heart failure and do not support a role for the renin-angiotensin system in the development of tolerance to alpha-adrenergic blockade. This low response rate explains why most randomized double-blind trials of prazosin in heart failure have not been able to demonstrate a significant difference between patients treated with placebo and those receiving active drug.