Sole M J, Liew C C
Department of Medicine, Toronto General Hospital, Ontario, Canada.
Am J Cardiol. 1988 Oct 5;62(11):20G-24G. doi: 10.1016/0002-9149(88)90027-6.
The cardiomyopathic Syrian hamster has a genetically transmitted form of dilated cardiomyopathy and is an important paradigm of myocardial disease, particularly for studies addressing the earliest stages of myocardial dysfunction. This model exhibits an increase in cardiac sympathetic tone in the presence of an altered expression of sarcolemmal calcium channels or of alpha 1 receptors, and a defective handling of calcium by both cardiomyocytes and vascular smooth muscle cells. Increased expression of the oncogene c-myc is evident in cardiomyocytes before any overt evidence of heart disease. Alterations in a nuclear phosphoprotein, which appears to be important in the regulation of gene expression, have also been identified. The disease becomes phenotypically manifest by the development of microvascular spasm, reperfusion injury and myocyte loss. Myocyte loss, in turn, burdens the remaining cells with an increasing load, increasing sympathetic stimulation, myocyte hypertrophy and further cell loss--a continuing vicious spiral that culminates in the development of myocardial failure. All of the features of hamster cardiomyopathy may be prevented by the administration of verapamil or prazosin to juvenile hamsters before the phenotypic onset of their heart disease. This understanding has led to the study of new imaging agents that promise the detection of such forms of cardiomyopathy in their earliest stages and a means by which the effects of therapy can be assessed. If such mechanisms are applicable to human cardiomyopathy, early treatment of patients with adrenergic antagonists or calcium antagonists should be beneficial.
患有心肌病的叙利亚仓鼠有一种基因遗传性扩张型心肌病，是心肌疾病的重要范例，尤其适用于研究心肌功能障碍的最早阶段。该模型在肌膜钙通道或α1受体表达改变的情况下，心脏交感神经张力增加，心肌细胞和血管平滑肌细胞对钙的处理存在缺陷。在心脏病出现任何明显迹象之前，心肌细胞中癌基因c-myc的表达就明显增加。还发现了一种核磷蛋白的改变，这种改变似乎在基因表达调控中很重要。微血管痉挛、再灌注损伤和心肌细胞丢失的发展使该疾病在表型上显现出来。心肌细胞丢失反过来又使其余细胞负担加重，交感神经刺激增加，心肌细胞肥大，进一步导致细胞丢失——这是一个持续的恶性循环，最终导致心力衰竭。在幼年仓鼠心脏病表型出现之前，给它们服用维拉帕米或哌唑嗪可以预防仓鼠心肌病的所有特征。这种认识促使人们研究新的成像剂，有望在心肌病的最早阶段检测到这种疾病，并提供一种评估治疗效果的方法。如果这些机制适用于人类心肌病，那么用肾上腺素能拮抗剂或钙拮抗剂对患者进行早期治疗应该是有益的。
