卡维地洛对扩张型心肌病大鼠心功能及心脏肾上腺素能神经元损伤的影响

Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy.

作者信息

Watanabe Kenichi, Takahashi Toshihiro, Nakazawa Mikio, Wahed Mir I I, Fuse Koichi, Tanabe Naohito, Kodama Makoto, Aizawa Yoshifusa, Ashino Hiroki, Tazawa Shusaku

机构信息

Department of Clinical Pharmacology, Niigata College of Pharmacy, Kamisinei-cho, Niigata 950-2081, Japan.

出版信息

J Nucl Med. 2002 Apr;43(4):531-5.

PMID:11937598

Abstract

UNLABELLED

Metaiodobenzylguanidine (MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating beta-adrenoceptor-blocking agent, were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis.

METHODS

Twenty-eight days after immunization, surviving rats (41/55, or 75%) were divided into 2 groups treated with carvedilol, 2 mg/kg/d (group C, n = 19), or vehicle alone (0.5% methylcellulose, group V, n = 22). After oral administration for 2 mo, heart weight, heart rate, left ventricular end-diastolic pressure (LVEDP), and myocardial fibrosis were measured and compared with those in untreated rats (group N, n = 19). Myocardial uptake of (125)I-MIBG (differential absorption ratio) in the left ventricle was measured by autoradiography at 10, 30, or 240 min after tracer injection.

RESULTS

Four (18%) of 22 rats in group V died between days 28 and 84 after immunization. None of the rats in group C or N died. Heart weight, heart rate, LVEDP, and area of myocardial fibrosis in group C (1.14 +/- 0.04 g, 345 +/- 16 beats per minute, 7.6 +/- 1.5 mm Hg, and 12% +/- 1%) were significantly lower than those in group V (1.34 +/- 0.04 g, 389 +/- 10 beats per minute, 12.3 +/- 1.3 mm Hg, and 31% +/- 2%). Although the differential absorption ratio was lower at all time points in group V than in group N, uptake after treatment increased in group C, compared with group V, at 10 min (12.5 +/- 1.0 vs. 7.6 +/- 0.8, not significant), 30 min (10.1 +/- 1.1 vs. 6.3 +/- 0.9, not significant), and 240 min (6.5 +/- 0.5 vs. 2.5 +/- 0.2, P < 0.05). The late washout ratio from myocardial radioactivity between 30 and 240 min in group C was lower than that in group V (36% vs. 60%).

CONCLUSION

These observations indicated that carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.

摘要

未标记

间碘苄胍（MIBG）是检测心力衰竭中心脏肾上腺素能神经元损伤的可靠标志物。在自身免疫性心肌炎后扩张型心肌病大鼠模型中研究了卡维地洛（一种血管舒张性β肾上腺素能受体阻滞剂）的心脏保护特性。

方法

免疫后28天，存活的大鼠（41/55，即75%）分为两组，一组用卡维地洛治疗，剂量为2mg/kg/d（C组，n = 19），另一组仅用赋形剂（0.5%甲基纤维素，V组，n = 22）。口服给药2个月后，测量心脏重量、心率、左心室舒张末期压力（LVEDP）和心肌纤维化，并与未治疗的大鼠（N组，n = 19）进行比较。在注射示踪剂后10、30或240分钟，通过放射自显影测量左心室心肌对（125）I-MIBG的摄取（差异吸收率）。

结果

V组22只大鼠中有4只（18%）在免疫后28至84天死亡。C组和N组均无大鼠死亡。C组的心脏重量、心率、LVEDP和心肌纤维化面积（1.14±0.04g，345±16次/分钟，7.6±1.5mmHg，12%±1%）显著低于V组（1.34±0.04g，389±10次/分钟，12.3±1.3mmHg，31%±2%）。尽管V组在所有时间点的差异吸收率均低于N组，但与V组相比，C组治疗后的摄取在10分钟时增加（12.5±1.0对7.6±0.8，无显著性差异），30分钟时增加（10.1±1.1对6.3±0.9，无显著性差异），240分钟时增加（6.5±0.5对2.5±0.2，P<0.05）。C组在30至240分钟之间心肌放射性的晚期洗脱率低于V组（36%对60%）。