Sladek T, Sladkova J, Kolar F, Papousek F, Cicutti N, Korecky B, Rakusan K
Department of Physiology, University of Ottawa, Ont., Canada.
Cardiovasc Res. 1996 Apr;31(4):568-76.
The aim was to study the effect of the AT1 receptor antagonist losartan on hemodynamic and morphometric changes following experimental infarction.
Experimental infarction was produced in adult male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarction and sham-operated animals.
Infarcted hearts were characterized by significant decreases in left ventricular developed pressure, as well as positive and negative (dP/dt)max, whereas left ventricular end-diastolic pressure (LVEDP), relaxation constant tau and right ventricular systolic pressure (RVSP) significantly increased. Treatment with losartan decreased the LVEDP, the relaxation constant tau and RVSP in the infarcted hearts. Right ventricular weight significantly increased in rats with infarction; this was attenuated by losartan. Infarct size was not significantly influenced by losartan treatment. Morphometric data revealed decreased capillary supply in infarcted hearts, especially in regions close to infarction; the decrease was less pronounced after losartan treatment. Capillary density in near infarct region decreased from 2826/mm2 to 1471/mm2 in untreated animals but in the treated animals it decreased from 2982/mm2 to only 2037/mm2. Simultaneous significant decrease in myocyte-to-capillary ratio in treated animals compared to untreated rats (0.87 to 0.67) seems to indicate formation of new capillary channels after losartan treatment. LVEDP was dependent on the size of infarction in untreated but not in treated animals. A close correlation between LVEDP and capillary density was found.
Decreased ventricular contractility, prolonged relaxation and decreased coronary capillary density in rat experimental cardiac infarction confirm and amplify previous reports dealing with this experimental model. Moreover, we have found evidence of improved hemodynamics and coronary angiogenesis after losartan treatment.
研究血管紧张素Ⅱ1型（AT1）受体拮抗剂氯沙坦对实验性梗死心肌血流动力学及形态学改变的影响。
成年雄性大鼠通过结扎冠状动脉造成实验性梗死。将氯沙坦治疗组与未治疗的梗死大鼠对照组及假手术动物进行比较。
梗死心脏的特征为左心室舒张末压、正负最大压力变化速率（dP/dt）max显著降低，而左心室舒张末压（LVEDP）、舒张常数τ和右心室收缩压（RVSP）显著升高。氯沙坦治疗可降低梗死心脏的LVEDP、舒张常数τ和RVSP。梗死大鼠右心室重量显著增加；氯沙坦可减轻此现象。氯沙坦治疗对梗死面积无显著影响。形态学数据显示梗死心脏的毛细血管供应减少，尤其是在梗死灶附近区域；氯沙坦治疗后减少程度较轻。未治疗动物梗死灶附近区域的毛细血管密度从2826/mm²降至1471/mm²，而治疗动物从2982/mm²仅降至2037/mm²。与未治疗大鼠相比，治疗动物的心肌细胞与毛细血管比率同时显著降低（从0.87降至0.67），这似乎表明氯沙坦治疗后形成了新的毛细血管通道。在未治疗动物中，LVEDP取决于梗死面积，而在治疗动物中则不然。LVEDP与毛细血管密度之间存在密切相关性。
大鼠实验性心肌梗死中心室收缩力降低、舒张延长及冠状动脉毛细血管密度降低，证实并扩展了以往关于该实验模型的报道。此外，我们发现氯沙坦治疗后有血流动力学改善和冠状动脉血管生成的证据。
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