https://scholars.lib.ntu.edu.tw/handle/123456789/192267
標題: | Pravastatin 對於已用CS-866治療之心肌梗塞大鼠其心室再塑型之影響探討(1/2) Effect of Pravastatin on Left Ventr icular Remodeling in CS866-treated Rats with Myocardial Infarction |
作者: | 蔡長和 | 關鍵字: | 心律不整;肥厚;心肌梗塞;心肌細胞;Arrhythmias;Hypertrophy;Myocardial infarction;Myocytes | 公開日期: | 31-七月-2003 | 出版社: | 臺北市:國立臺灣大學醫學院外科 | 摘要: | 心肌梗塞後之心肌細胞增厚係引起心律不整之重要原因。血管收縮素接受 體拮抗劑和statins 二者皆可降低心血管之死亡率。二者併用時,是否會比單一使 用在減少心肌肥厚效果上更好呢?不得而知。 在綁完左前降冠狀動脈後,大鼠分成餵食CS866 (0.01, 0.1, 1 和2 mg/kg per day)或pravastatin (5 mg/kg per day)或兩者共計四週。此兩種藥當單獨給予時皆可 降低梗塞邊緣的心肌肥厚現象。若兩者合用時,則減低效果更明顯。 心肌之內皮素-1 在邊緣區比正常組高6.5 倍。而加入pravastatin 後,內皮素 濃度則下降。當併用低濃度的CS866 (0.01 mg/kg per day) 比單獨使用pravastatin 更能減低心肌細胞肥厚變化。而使用最高濃度的CS866 (2 mg/kg per day)併用 者,則有最明顯的減低心肌肥厚變化,雖然其內皮素-1 濃度沒有明顯地下降。而 心律不整之分數反映出心肌肥厚程度。 併用pravastatin 和CS866 可依劑量變化而減低心肌肥厚程度。此乃因透過 不同之作用機轉,進而降低心律不整之發生。這種現象提供併用藥物之治療契機。 Background— Reactive cardiomyocyte hypertrophy after myocardial infarction is an important risk factor for arrhythmias. Both angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to decrease cardiovascular morbidity and mortality. Whether combination treatment may be superior to either drug alone on cardiomyocyte hypertrophy remains unclear. Methods and Results— After ligation of the left anterior descending artery, rats were randomized to both, 1, or neither of the angiotensin receptor antagonist Cs866 (0.01, 0.1, 1, and 2 mg/kg per day) and HMG-CoA reductase inhibitor pravastatin (5 mg/kg/day) for four weeks. Each drug, when given alone, decreased cardiomyocyte sizes isolated by enzymatic dissociation at the border zone compared with vehicles. However, compared with either drug alone, combined Cs866 and pravastatin prevent cardiomyocyte hypertrophy to a larger extent. The myocardial endothelin-1 levels at the border zone were 6.5-fold higher (P <0.0001) in the vehicle group compared with the sham group, which can be inhibited after pravastatin administration. Further evaluation of combination therapy with a low dose of Cs866 (0.01 mg/kg/day) significantly prevented cardiomyocyte hypertrophy compared with pravastatin alone (3020 ± 368 vs. 3202 ± 406 mm2 in the pravastatin-treated group, P = 0.04). With the highest dose of Cs866 (2 mg/kg/day) in combined therapy, we observed a further reduction of cardiomyocyte hypertrophy although tissue endothelin-1 levels remained stable in combination groups. Measurements of arrhythmic score mirrored those of cardiomyocyte hypertrophy. Conclusions— Dual-therapy with pravastatin and Cs866, which produced an additive reduction in cardiomyocyte hypertrophy in a dose-dependent manner after myocardial infarction through different mechanisms, decreases the propensity of the heart to arrhythmogenesis. Because cotreatment with statins and Cs866 acts in an additive manner, these observations provide important therapeutic implications in pharmacotherapy of clinical practice. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/24492 | 其他識別: | 912314B002227 | Rights: | 國立臺灣大學醫學院外科 |
顯示於: | 醫學系 |
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912314B002227.pdf | 147.04 kB | Adobe PDF | 檢視/開啟 |
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