Kobayashi A, Yamashita T, Kaneko M, Nishiyama T, Hayashi H, Yamazaki N
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka Prefecture, Japan.
J Am Coll Cardiol. 1987 Nov;10(5):1128-38. doi: 10.1016/s0735-1097(87)80356-x.
The Bio 14.6 Syrian hamster provides a good model for experimental study of cardiomyopathy. Cardiac receptor binding sites (alpha-1-, beta- and calcium antagonists) were studied in early (21 days old) and late (70 days old) stages of cardiomyopathy. The effects of verapamil on histologic features and free radicals in the heart were studied. The number of alpha-1- and beta-cardiac receptor binding sites was significantly greater in the late stage of cardiomyopathy when compared with findings in normal golden hamsters used as controls. The calcium antagonist receptors were significantly increased in the early stage but alpha-1- and beta-receptors were not. Verapamil-treated hamsters received intraperitoneal injections of verapamil at a dose of 5 mg/kg per day for 70 days from age 20 days. The percent areas of fibrosis and calcification in the verapamil-treated group were significantly smaller than those in the control group. The concentrations of lipid peroxides in the whole heart and free radicals in the heart mitochondria were significantly higher in the cardiomyopathic hamsters, and verapamil inhibited the increase in free radical concentration in the hearts of these hamsters. This study confirms that the number of calcium channels is increased early in the course of cardiomyopathy in the Bio 14.6 Syrian hamster. A larger number of free radicals may participate in the accumulation of calcium and cell injury in the myocytes of these hamsters. Verapamil protects against myocardial damage and may do so by inhibiting voltage-dependent calcium uptake and by preventing cell injury from free radicals.
Bio 14.6叙利亚仓鼠为心肌病的实验研究提供了一个良好的模型。在心肌病的早期(21日龄)和晚期(70日龄)研究了心脏受体结合位点(α-1、β和钙拮抗剂)。研究了维拉帕米对心脏组织学特征和自由基的影响。与用作对照的正常金黄仓鼠相比,心肌病晚期的α-1和β心脏受体结合位点数量显著增加。钙拮抗剂受体在早期显著增加,但α-1和β受体没有增加。维拉帕米治疗的仓鼠从20日龄开始,每天腹腔注射5mg/kg的维拉帕米,持续70天。维拉帕米治疗组的纤维化和钙化面积百分比显著小于对照组。心肌病仓鼠的全心中脂质过氧化物浓度和心脏线粒体中的自由基浓度显著更高,维拉帕米抑制了这些仓鼠心脏中自由基浓度的增加。这项研究证实,在Bio 14.6叙利亚仓鼠心肌病病程早期钙通道数量增加。大量自由基可能参与了这些仓鼠心肌细胞中钙的积累和细胞损伤。维拉帕米可预防心肌损伤,可能是通过抑制电压依赖性钙摄取和防止自由基引起的细胞损伤来实现的。