Department of Medicine, Section of Cardiology, Southern Arizona VA Health Care System, the Sarver Heart Center, The University of Arizona, Tucson, AZ, USA.
J Cardiovasc Pharmacol. 2012 Sep;60(3):293-8. doi: 10.1097/FJC.0b013e31825f6f88.
Poloxamer-188 (P-188) is a biological membrane sealant that prevents the unregulated entry of Ca into cardiomyocytes and has been shown to have the ability to act as a membrane-repair agent in isolated cardiac myocytes. The purpose of this study was to determine if treatment with P-188 would improve left ventricular (LV) function in a rat chronic heart failure (CHF) model.
We ligated the left coronary artery of adult male Sprague-Dawley rats to induce a myocardial infarction (MI). The rats were allowed to recover for 8 weeks until stable CHF was present and treated with a range of P-188 doses [1.5 mg/kg (N = 6), 4.6 mg/kg (N = 11), 15.3 mg/kg (N = 11), and 460 mg/kg (N = 6)] delivered via 30 minutes of intravenous infusion. The rats were randomized to study groups: control, 2 hours, 24 hours, 48 hours, 1 week, and 2 weeks posttreatment (N = 8 in each group).
Two weeks after high dose (460 mg/kg) administration, P-188 improved (P < 0.05) left ventricular ejection fraction from 34% to 51%, which persisted over 38 hours and decreased (P < 0.05) LV end systolic diameter from 0.9 ± 0.07 to 0.6 ± 0.08 cm, in the rats with CHF. There was no statistical change in hemodynamics. Additionally, P-188 reduced (P < 0.05) circulating troponin levels 2 weeks after treatment.
Treatment with P-188 improves the LV function and partially reverses maladaptive LV remodeling in rats with moderate CHF after MI. These data introduce the idea of using a biological membrane sealant as a new approach to treating CHF after MI.
泊洛沙姆 188（P-188）是一种生物膜密封剂，可防止 Ca 不受调节地进入心肌细胞，并已被证明具有作为分离心肌细胞中膜修复剂的能力。本研究的目的是确定 P-188 治疗是否会改善大鼠慢性心力衰竭（CHF）模型中的左心室（LV）功能。
我们结扎成年雄性 Sprague-Dawley 大鼠的左冠状动脉以诱导心肌梗死（MI）。大鼠允许恢复 8 周，直到出现稳定的 CHF，并接受一系列 P-188 剂量[1.5mg/kg（N=6），4.6mg/kg（N=11），15.3mg/kg（N=11）和 460mg/kg（N=6）]通过 30 分钟的静脉输注给药。大鼠随机分为对照组、2 小时组、24 小时组、48 小时组、1 周组和 2 周组（每组 N=8）。
高剂量（460mg/kg）给药后 2 周，P-188 改善（P<0.05）CHF 大鼠的左心室射血分数从 34%提高至 51%，持续 38 小时以上，并降低（P<0.05）LV 收缩末期直径从 0.9±0.07cm 降低至 0.6±0.08cm。血流动力学无统计学变化。此外，P-188 降低了治疗后 2 周时循环肌钙蛋白水平（P<0.05）。
P-188 治疗可改善 LV 功能并部分逆转 MI 后中度 CHF 大鼠的适应性 LV 重构。这些数据提出了使用生物膜密封剂作为 MI 后 CHF 新治疗方法的想法。
