The novel calcium antagonist Ro 40-5967 limits myocardial infarct size in the dog.
The novel calcium antagonist Ro 40-5967 limits myocardial infarct size in the dog.
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新型钙拮抗剂 Ro 40-5967 限制了狗的心肌梗塞面积。
DOI：
10.1093/cvr/28.10.1526
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发表时间：
1994
影响因子：
10.8
通讯作者：
Reimer,KA
中科院分区：
文献类型：
--
作者：
VanderHeide,RS;Schwartz,LM;Reimer,KA
目的：比较新型钙拮抗剂Ro 40-5967（Ro 40）与维拉帕米（Verapamil）和缺血预处理（ischaemic preconditioning）对心肌梗死的限制作用，Ro 40 - 5967是一种新型的钙拮抗剂，具有很小的负性肌力作用。给药组犬在阻断前15 min开始静脉注射维拉帕米（1.0 mg·kg-1）或Ro 40（3.0 mg·kg-1）100 min。对照犬接受盐水输注。缺血预处理包括4个5 min缺血循环和4个5 min再灌注循环。再流3小时后，切除心脏，用氯化三苯基四氮唑宏观化学法测量梗死面积，并表示为缺血危险区（AAR）的百分比。为了控制梗死面积的变化，由于侧支血流量的变化，各组之间的梗死面积进行了比较，使用ANCOVA，其中梗死面积和侧支血流量，在30分钟的闭塞测量，分别为因变量和自变量，respectively，Results：血管侧支血流量和AAR没有显着差异的任何组之间。对照犬（n=13）的平均梗死面积（通过ANCOVA调整组间侧支血流的轻微差异）为AAR的25.9%（SEM 3.2）。维拉帕米（n= 11）和Ro 40（n = 9）均限制了梗死面积[分别为14.2（3.2）% AAR和16.7（2.9）% AAR;均p<0.05]。预处理（n = 17）也显著限制了梗死面积[8.1（1.8）%; p<0.01]。结论：新的钙拮抗剂Ro 40-5967在限制局部缺血60分钟后再灌注3小时的梗死面积方面与维拉帕米一样有效，尽管这两种钙拮抗剂都不如缺血预处理有效。Cardiovascular Research 1994;28：1526-1532
Objective:The aim was to compare the infarct limiting effect of Ro 40-5967 (Ro40), a new calcium antagonist with little negative inotropic activity, with that of verapamil and with ischaemic preconditioning, a potent endogenous cardioprotective mechanism.Methods:Dogs (n = 53) of either sex were subjected to 60 min of coronary occlusion followed by 3 h of reperfusion. Drug treated dogs received either verapamil (1.0 mg·kg−1) or Ro40 (3.0 mg·kg−1) intravenously for 100 min starting 15 min prior to the occlusion. Control dogs received a saline infusion. Ischaemic preconditioning consisted of four 5 min cycles of ischaemia alternating with four 5 min cycles of reperfusion. After 3 h of reflow, hearts were excised and infarct size was measured using tripheyltetrazolium chloride macrochemistry and expressed as percent of the ischaemic area at risk (AAR). To control for variation in infarct size due to variation in collateral blood flow, infarct size among groups was compared using ANCOVA, in which infarct size and collateral blood flow, measured at 30 min of occlusion, were dependent and independent variables, respectively.Results:Transmural collateral blood flow and AAR were not significantly different between any of the groups. Mean infarct size (adjusted by ancova for slight differences in collateral blood flow among groups) in control dogs (n=13) was 25.9(SEM 3.2)% of the AAR. Both verapamil (n= 11) and Ro40 (n = 9) limited infarct size [14.2(3.2)% AAR and 16.7(2.9)% AAR, respectively; both p<0.05]. Preconditioning (n = 17) also significantly limited infarct size [8.1(1.8)%; p<0.01].Conclusions:The new calcium antagonist, Ro 40-5967, was as effective as verapamil in limiting infarct size after 60 min of regional ischaemia followed by 3 h of reperfusion, although neither calcium antagonist was as effective as ischaemic preconditioning.Cardiovascular Research1994;28:1526-1532