Evaluation of the effect of metoprolol on energy metabolism in the ischaemic myocardium in relation to regional myocardial blood flow.

Evaluation of the effect of metoprolol on energy metabolism in the ischaemic myocardium in relation to regional myocardial blood flow.
复制标题

评估美托洛尔对缺血心肌能量代谢与局部心肌血流量的影响。

DOI:
10.1093/cvr/21.9.660
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发表时间:
1987
影响因子:
10.8
通讯作者:
N. Sakamoto
N. Sakamoto
中科院分区:
医学1区
文献类型:
--
作者:
M. Nanki;K. Itoh;T. Matsubara;K. Nishimura;T. Kambe;S. Sugiyama;T. Ozawa;N. Sakamoto

文献摘要

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为了评价β受体阻滞剂对缺血心肌能量代谢的影响,在冠状动脉结扎后20分钟给24只麻醉犬注射0.2或0.5 mg.kg-1剂量的酒石酸美托洛尔或生理盐水。采用氢气清除法测量局部心肌血流量,记录心率和主动脉压。冠状动脉闭塞60分钟后,从记录心肌血流的五个区域取出心肌活检样本,以确定其5'-三磷酸腺苷(ATP)的含量。还测量了从缺血和非缺血心肌分离的线粒体的呼吸功能和酰基辅酶A含量。对照组心肌血流量小于20 ml.min-1.100 g-1的严重缺血心肌中ATP含量降至非缺血区的27.5%,而给予美托洛尔0.5 mg.kg-1则使ATP含量维持在46.3%。在缺血心肌中,美托洛尔抑制线粒体中长链酰基辅酶A的积累,并显着保留其呼吸功能。相比之下,当流量小于60ml.min-1.100g-1时,美托洛尔不影响心肌血流量。美托洛尔可按剂量比例降低心率,但平均主动脉压没有改变。这些结果表明,β阻滞剂对缺血心肌的能量代谢具有有益的作用,这种作用可能不仅是由于心脏做功的减少,而且是由于缺血心肌中脂肪酸代谢的恶性循环的减少。
To evaluate the effect of beta blockade on energy metabolism in ischaemic myocardium metoprolol tartrate in doses of 0.2 or 0.5 mg.kg-1 or saline was injected into 24 anaesthetised dogs 20 min after coronary ligation. Regional myocardial blood flow was measured by the hydrogen gas clearance method, and the heart rate and aortic pressure were recorded. After 60 min coronary occlusion myocardial biopsy specimens were removed from five areas where myocardial blood flow had been recorded to determine their content of adenosine-5'-triphosphate (ATP). Respiratory function and acyl-coenzyme A contents of mitochondria isolated from ischaemic and non-ischaemic myocardium were also measured. In the control group the ATP content in severely ischaemic myocardium where myocardial blood flow was less than 20 ml.min-1.100 g-1 was decreased to 27.5% of that in the non-ischaemic area, whereas the administration of metoprolol 0.5 mg.kg-1 maintained ATP content at 46.3%. In ischaemic myocardium metoprolol inhibited the accumulation of long chain acyl-coenzyme A in mitochondria and significantly preserved their respiratory function. In contrast, metoprolol did not affect myocardial blood flow in myocardium where flow was less than 60 ml.min-1.100 g-1. Heart rate was decreased by metoprolol in proportion to the dose, whereas mean aortic pressure was not changed. These results suggest that beta blockade had beneficial effects on the energy metabolism of ischaemic myocardium and that such effects might be due not only to a reduction in cardiac work but also to a reduction in the vicious circle of fatty acid metabolism in ischaemic myocardium.