Morales C, Rodríguez M, Scapín O, Gelpi R J
Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Mol Cell Biochem. 1998 Sep;186(1-2):117-21.
The aim was to determine whether enalaprilat (0.08 mg/kg/min) or losartan (0.01 mg/kg/min) administration before ischemia can improve postischemic systolic and diastolic dysfunction ('stunned myocardium') and attenuate the 'hyperfunction' phase at the beginning of reperfusion. An isolated isovolumic rabbit heart preparation was subjected to 15 min of ischemia followed by 30 min of reperfusion without (group 1) or with pretreatment with enalaprilat (group 2) or losartan (group 3). Left ventricular developed pressure and end-diastolic pressure (diastolic stiffness) were measured and the time constant of isovolumic relaxation (T, Tau) and the ratio between +dP/dt and -dP/dt were calculated. In comparison to the stunned group (group 1) both enalaprilat (group 2) and losartan (group 3) exerted a significant protective effect on postischemic recovery of contractile state and diastolic stiffness. Only enalaprilat attenuated the 'hypercontractile' phase. However, both enalaprilat and losartan failed to improve myocardial relaxation. In summary, these data strongly suggest a direct deleterious action of the local renin-angiotensin system on ischemic myocardium and diminution of myocardial stunning with its successful blockade. Although, we can not exclude the possibility that bradykinin has some cardioprotective effect, these data suggest that angiotensin exacerbates myocardial injury.
目的是确定在缺血前给予依那普利拉（0.08毫克/千克/分钟）或氯沙坦（0.01毫克/千克/分钟）是否能改善缺血后收缩和舒张功能障碍（“心肌顿抑”），并减轻再灌注开始时的“功能亢进”阶段。将离体兔等容心脏标本进行15分钟缺血，然后进行30分钟再灌注，分为未预处理组（第1组）、依那普利拉预处理组（第2组）或氯沙坦预处理组（第3组）。测量左心室舒张末压和舒张末压力（舒张硬度），并计算等容舒张时间常数（T，Tau）以及 +dP/dt 与 -dP/dt 的比值。与顿抑组（第1组）相比，依那普利拉（第2组）和氯沙坦（第3组）对缺血后收缩状态和舒张硬度的恢复均具有显著的保护作用。只有依那普利拉减轻了“高收缩”阶段。然而，依那普利拉和氯沙坦均未能改善心肌舒张。总之，这些数据强烈提示局部肾素 - 血管紧张素系统对缺血心肌有直接有害作用，阻断该系统可减轻心肌顿抑。虽然我们不能排除缓激肽具有某些心脏保护作用的可能性，但这些数据提示血管紧张素会加重心肌损伤。
