在缺血再灌注离体大鼠心脏中进行冠状静脉药物输注。

Coronary venous drug infusion in the ischaemic-reperfused isolated rat heart.

作者信息

Uriuda Y, Wang Q D, Li X S, Sjoquist P O, Nordlander R, Ryden L

机构信息

Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.

出版信息

Cardiovasc Res. 1996 Jan;31(1):82-92.

PMID:8849592

Abstract

OBJECTIVES

Coronary venous retroinfusion (CVR) has been used experimentally in large animals for selective drug delivery into ischaemic myocardium. It would be an advantage if CVR could also be used in isolated perfused rat heart models. The aim of the present paper is to develop a regional ischaemic model in the isolated perfused rat heart combined with CVR.

METHOD

Pharmacokinetic study: The spatial distribution of retrogradely infused felodipine (used as a tracer) during regional myocardial ischaemia was investigated. Following occlusion of the left coronary artery, felodipine was administered over a period of 5 min by CVR. Ischaemia-reperfusion study: Following 30 min of stabilisation, 14 rat hearts were subjected to 60 min of regional ischaemia followed by 60 min of reperfusion. Felodipine (0.7 nmol/kg, n = 7) or vehicle (n = 7) was administered by means of CVR. The infusion was given during the last 5 min of ischaemia at a rate of 0.6 ml/min.

RESULTS

Pharmacokinetic study: By means of CVR, the compound was distributed specifically into the ischaemic myocardium. The highest tissue concentration was obtained when the coronary vein was occluded during CVR. The maximal concentration in the ischaemic myocardium was 20-70 times that in the non-ischaemic areas. A transmyocardial gradient was noted with higher drug concentration in the subepicardial zone. Ischaemia-reperfusion study: At the end of reperfusion, the recovery of coronary flow, left ventricular developed pressure and double product (DP; LVDP x HR) was 101 +/- 7% (mean +/- s.e.m.), 99 +/- 8% and 98 +/- 4% of the pre-ischaemic values, respectively. This was significantly different from the vehicle group (78 +/- 5, P < 0.05, 74+/- 6, P < 0.01 and 78 +/- 3, P < 0.05).

CONCLUSION

CVR could easily be accomplished in the isolated perfused rat heart. The drug was specifically delivered into the ischaemic myocardium. Felodipine exerted a myocardioprotective effect in isolated rat hearts subjected to 60 min of regional ischaemia followed by 60 min of reperfusion.

摘要

目的

冠状动脉逆行灌注（CVR）已在大型动物实验中用于向缺血心肌选择性给药。如果CVR也能用于离体灌注大鼠心脏模型，将是一个优势。本文的目的是建立一种结合CVR的离体灌注大鼠心脏局部缺血模型。

方法

药代动力学研究：研究局部心肌缺血期间逆行灌注非洛地平（用作示踪剂）的空间分布。左冠状动脉闭塞后，通过CVR在5分钟内给予非洛地平。缺血再灌注研究：在稳定30分钟后，14只大鼠心脏进行60分钟的局部缺血，然后再灌注60分钟。通过CVR给予非洛地平（0.7 nmol/kg，n = 7）或赋形剂（n = 7）。在缺血的最后5分钟以0.6 ml/min的速率进行输注。

结果

药代动力学研究：通过CVR，该化合物特异性分布到缺血心肌中。当CVR期间冠状静脉闭塞时获得最高组织浓度。缺血心肌中的最大浓度是非缺血区域的20 - 70倍。观察到跨心肌梯度，心外膜下区域药物浓度较高。缺血再灌注研究：再灌注结束时，冠状动脉血流、左心室舒张末压和双乘积（DP；LVDP×HR）的恢复分别为缺血前值的101±7%（平均值±标准误）、99±8%和98±4%。这与赋形剂组有显著差异（78±5，P < 0.05；74±6，P < 0.01；78±3，P < 0.05）。