Gray Rosaire P, Turner Mark A, Sheridan Desmond J, Fry Christopher H
Department of Medicine, University College London, 48 Riding House St, London W1P 7PN, UK.
Cardiovasc Res. 2007 Feb 1;73(3):539-48. doi: 10.1016/j.cardiores.2006.11.017. Epub 2006 Nov 18.
The aims of this study were to: i) investigate the role of angiotensin in mediating changes to myocardial electromechanical properties during the development and regression of left ventricular hypertrophy (LVH) generated by constriction of the thoracic aorta; ii) identify any role of angiotensin-1 receptor blockade on ameliorating changes to these electromechanical properties.
LVH was induced in guinea-pigs by constricting the ascending aorta (AC groups). After 42+/-3 days, the constriction was either removed or left in place. Following the second operation animals were fed losartan (10 mg x kg(-1) x day(-1)) or saline for 42+/-3 days. Sham-operated animals served as controls. In other groups, LVH was generated by subcutaneous angiotensin II (200 ng x kg(-1) x min(-1)) infusion for 42+/-3 days with or without losartan administration (AT groups), and compared to animals undergoing aortic constriction for a similar period. Electromechanical changes were recorded in isolated left ventricular myocardial preparations.
Wet and dry heart-to-body weight ratios (HBR) increased significantly in the AC and AT models compared to control. Losartan prevented the increase of HBR in the AT group. Removal of the constriction allowed LVH to regress to control. The force-frequency relationship was reduced in both models and recovered fully on regression. However, the two models generated different electrophysiological changes: in the AC group, longitudinal conduction velocity was reduced and transverse conduction increased, with a consequent reduction of the anisotropic conduction ratio. On regression recovery was only partial; action potential duration was prolonged and did not recover. In the AT group, electrophysiological changes were limited: only an increase of transverse conduction and a reduction of the anisotropic conduction ratio were observed. Losartan had no effect on HBR or electromechanical variables in the aortic constricted animals, nor did it affect the extent of recovery in animals with regression of LVH.
The electromechanical changes to hypertrophied myocardium are different in these two models of LVH. Moreover, losartan was ineffective in modulating the consequences of hypertrophy induced by constriction of the thoracic aorta.
本研究旨在：i）研究血管紧张素在胸主动脉缩窄所致左心室肥厚（LVH）发生及消退过程中介导心肌机电特性变化的作用；ii）确定血管紧张素-1受体阻断在改善这些机电特性变化方面的作用。
通过缩窄升主动脉在豚鼠中诱导LVH（AC组）。42±3天后，移除缩窄环或保留不变。第二次手术后，动物喂食氯沙坦（10mg·kg⁻¹·天⁻¹）或生理盐水42±3天。假手术动物作为对照。在其他组中，通过皮下输注血管紧张素II（200ng·kg⁻¹·分钟⁻¹）42±3天，有或无氯沙坦给药来诱导LVH（AT组），并与同期接受主动脉缩窄的动物进行比较。在离体左心室心肌标本中记录机电变化。
与对照组相比，AC和AT模型中湿重和干重心脏与体重比（HBR）显著增加。氯沙坦可防止AT组HBR升高。移除缩窄环可使LVH消退至对照水平。两个模型中的力-频率关系均降低，消退时完全恢复。然而，两个模型产生了不同的电生理变化：在AC组中，纵向传导速度降低，横向传导增加，导致各向异性传导率降低。消退时仅部分恢复；动作电位时程延长且未恢复。在AT组中，电生理变化有限：仅观察到横向传导增加和各向异性传导率降低。氯沙坦对主动脉缩窄动物的HBR或机电变量无影响，也不影响LVH消退动物的恢复程度。
这两种LVH模型中肥厚心肌的机电变化不同。此外，氯沙坦在调节胸主动脉缩窄所致肥厚的后果方面无效。
