Dedkov Eduard I, Zheng Wei, Christensen Lance P, Weiss Robert M, Mahlberg-Gaudin Florence, Tomanek Robert J
Department of Biomedical Sciences, New York College of Osteopathic Medicine/NYIT, Old Westbury, NY 11568, USA.
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H590-8. doi: 10.1152/ajpheart.00047.2007. Epub 2007 Mar 23.
We tested the hypothesis that chronically reducing the heart rate in infarcted middle-aged rats using ivabradine (IVA) would induce arteriolar growth and attenuate perivascular collagen and, thereby, improve maximal perfusion and coronary reserve in the surviving myocardium. Myocardial infarction (MI) was induced in 12-mo-old male Sprague-Dawley rats, which were then treated with either IVA (10.5 mg.kg(-1).day(-1); MI + IVA) or placebo (MI) via intraperitoneal osmotic pumps for 4 wk. Four weeks of IVA treatment limited the increase in left ventricular end-diastolic pressure and the decrease in ejection fraction but did not affect the size of the infarct, the magnitude of myocyte hypertrophy, or the degree of arteriolar and capillary growth. However, treatment reduced interstitial and periarteriolar collagen in the surviving myocardium of MI + IVA rats. The reduced periarteriolar collagen content was associated with improvement in maximal myocardial perfusion and coronary reserve. Although the rates of proliferation of periarteriolar fibroblasts were similar in the MI and MI + IVA groups, the expression levels of the AT(1) receptor and transforming growth factor (TGF)-beta(1) in the myocardium, as well as the plasma level of the ANG II peptide, were lower in treated rats 14 days after MI. Therefore, our data reveal that improved maximal myocardial perfusion and coronary reserve in MI + IVA rats are most likely the result of reduced periarteriolar collagen rather than enhanced arteriolar growth.
使用伊伐布雷定（IVA）长期降低梗死中年大鼠的心率会诱导小动脉生长并减轻血管周围胶原蛋白，从而改善存活心肌中的最大灌注和冠状动脉储备。在12月龄雄性Sprague-Dawley大鼠中诱导心肌梗死（MI），然后通过腹腔渗透泵给予IVA（10.5 mg·kg⁻¹·天⁻¹；MI + IVA）或安慰剂（MI），持续4周。IVA治疗4周限制了左心室舒张末期压力的升高和射血分数的降低，但不影响梗死面积、心肌细胞肥大程度或小动脉和毛细血管生长程度。然而，治疗减少了MI + IVA大鼠存活心肌中的间质和小动脉周围胶原蛋白。小动脉周围胶原蛋白含量的降低与最大心肌灌注和冠状动脉储备的改善相关。虽然MI组和MI + IVA组小动脉周围成纤维细胞的增殖率相似，但在MI后14天，治疗组大鼠心肌中AT₁受体和转化生长因子（TGF）-β₁的表达水平以及血管紧张素II肽的血浆水平较低。因此，我们的数据表明，MI + IVA大鼠中最大心肌灌注和冠状动脉储备的改善最可能是小动脉周围胶原蛋白减少的结果，而不是小动脉生长增强的结果。
