Effects of AT1-receptor blockade on progression of left ventricular dysfunction in dogs with heart failure.
Effects of AT1-receptor blockade on progression of left ventricular dysfunction in dogs with heart failure.
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AT1 受体阻断对心力衰竭犬左心室功能障碍进展的影响。
DOI：
10.1152/ajpheart.1999.276.4.h1385
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Sabbah,HN
中科院分区：
文献类型：
--
作者：
Tanimura,M;Sharov,VG;Shimoyama,H;Mishima,T;Levine,TB;Goldstein,S;Sabbah,HN
本研究的目的是确定血管紧张素II AT1受体拮抗剂缬沙坦早期长期单药治疗对中度心力衰竭（HF）犬左心室（LV）功能障碍和重塑进展的影响。在30只患有多次连续冠状动脉内微栓塞引起的中度HF的犬中进行了研究。当LV射血分数为30 - 40%时，停止栓塞。最后一次栓塞后两周，将犬随机分为3个月的低剂量缬沙坦口服治疗组（400 mg，每日两次，n = 10）、高剂量缬沙坦口服治疗组（800 mg，每日两次，n = 10）或完全不治疗组（对照组，n = 10）。与对照组相比，缬沙坦治疗显著降低了平均主动脉压和左室舒张末期压。在未治疗的犬中，与随访前相比，随访3个月后左室射血分数降低（37 ± 1 vs. 29 ± 1%，P = 0.001），收缩末期容积（ESV）和舒张末期容积（EDV）增加（分别为81 ± 5 vs. 92 ± 5 ml，P <0.001; 51 ± 3 vs. 65 ± 3 ml，P = 0.001）。在接受低剂量缬沙坦治疗3个月的犬中，射血分数保持不变（治疗前与治疗后分别为37 ± 1%和38 ± 2%），ESV也是如此，但EDV则不然。高剂量缬沙坦治疗3个月后，犬的射血分数降低（35 ± 1 vs.31 ± 2%，P = 0.02），ESV和EDV增加，与对照组相当。缬沙坦对心肌细胞肥大或间质纤维化程度无显著影响。我们的结论是，对于中度HF犬，早期长期治疗与AT1受体阻滞剂缬沙坦减少前负荷和后负荷，但只有有限的好处，在衰减LV功能障碍和心室重构的进展。
The objective of the present study was to determine the effects of early long-term monotherapy with the angiotensin II AT1-receptor antagonist valsartan on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Studies were performed in 30 dogs with moderate HF produced by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction was 30–40%. Two weeks after the last embolization, dogs were randomized to 3 mo of oral therapy with low-dose valsartan (400 mg twice daily,n= 10), to high-dose valsartan (800 mg twice daily,n= 10), or to no treatment at all (control,n= 10). Treatment with valsartan significantly reduced mean aortic pressure and LV end-diastolic pressure compared with control. In untreated dogs, LV ejection fraction decreased (37 ± 1 vs. 29 ± 1%,P= 0.001) and end-systolic volume (ESV) and end-diastolic volume (EDV) increased (81 ± 5 vs. 92 ± 5 ml,P< 0.001; 51 ± 3 vs. 65 ± 3 ml,P= 0.001, respectively) after 3 mo of follow-up compared with those levels before follow-up. In dogs treated for 3 mo with low-dose valsartan, ejection fraction was preserved (37 ± 1 vs. 38 ± 2%, pretreatment vs. posttreatment) as was ESV but not EDV. In dogs treated for 3 mo with high-dose valsartan, ejection fraction decreased (35 ± 1 vs. 31 ± 2%,P= 0.02) and ESV and EDV increased in a manner comparable to those levels in controls. Valsartan had no significant effects on cardiomyocyte hypertrophy or on the extent of interstitial fibrosis. We conclude that, for dogs with moderate HF, early long-term therapy with the AT1-receptor blocker valsartan decreases preload and afterload but has only limited benefits in attenuating the progression of LV dysfunction and chamber remodeling.
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影响因子：
37.8
作者：
Menard, J;Campbell, DJ;Gonzales, MF
通讯作者：
Gonzales, MF
影响因子：
20.1
作者：
L. Meggs;J. Coupet;Harer Huang;W. Cheng;Peng Li;J. Capasso;J. Homcy;P. Anversa
通讯作者：
L. Meggs;J. Coupet;Harer Huang;W. Cheng;Peng Li;J. Capasso;J. Homcy;P. Anversa
在起搏引起的心力衰竭中通过酶抑制和特异性受体阻断来调节肾素-血管紧张素通路：II。
影响因子：
37.8
作者：
Spinale,FG;Mukherjee,R;Iannini,JP;Whitebread,S;Hebbar,L;Clair,MJ;Melton,DM;Cox,MH;Thomas,PB;deGasparo,M
通讯作者：
deGasparo,M
血管紧张素 II 受体亚型：选择性拮抗剂和功能相关物。
影响因子：
39.3
作者：
P. Timmermans;R. D. Smith
通讯作者：
R. D. Smith
影响因子：
37.8
作者：
CROZIER, I;IKRAM, H;RUCINSKA, E
通讯作者：
RUCINSKA, E