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犬急性缺血性心脏体内再灌注期间局部去甲肾上腺素释放和心律失常的闭塞时间依赖性

Occlusion time dependency of regional noradrenaline release and cardiac arrhythmias during reperfusion of acutely ischaemic heart in the dog in vivo.

作者信息

Yamaguchi N, Kimura T, Lamontagne D, de Champlain J, Nadeau R

机构信息

Research Centre, Faculty of Medicine, University of Montreal, Hôpital du Sacré-Coeur de Montréal, Canada.

出版信息

Cardiovasc Res. 1990 Aug;24(8):688-96. doi: 10.1093/cvr/24.8.688.

Abstract

STUDY OBJECTIVE

The aim was to study the occlusion time dependency of reperfusion induced increases in regional cardiac noradrenaline release from the ischaemic area in relation to the incidence of ventricular arrhythmias.

DESIGN

The left anterior descending coronary artery was ligated for 15, 30 and 60 min in three separate groups of dogs (n = 10 per group). Each occlusion period was followed by a 30 min reperfusion period. The coronary sinus and the epicardial vein running in parallel with the left anterior descending coronary artery were cannulated for measurement of noradrenaline and lactate.

EXPERIMENTAL MATERIAL

30 adult mongrel dogs, 22.5(SEM 1.1) kg, were used for the study. The animals were anaesthetised with sodium pentobarbitone.

MEASUREMENTS AND MAIN RESULTS

During occlusion, epicardial venous blood noradrenaline concentrations remained unchanged up to 30 min, but increased from 0.133(0.027) ng.ml-1 to 0.289(0.069) ng.ml-1 after 60 min of occlusion (p less than 0.05). However, epicardial venous blood lactate concentrations increased immediately upon occlusion, and remained elevated (p less than 0.05) during the whole period of occlusion in all groups. Neither noradrenaline nor lactate concentrations in coronary sinus blood increased during occlusion. During reperfusion, nine dogs showed early ventricular fibrillation. The highest incidence of fibrillation (n = 5/10) was found in the 15 min occlusion group, but the difference was not significant between groups. Epicardial venous blood noradrenaline concentrations increased to 0.371(0.076) ng.ml-1, 0.470(0.178) ng.ml-1, and 1.824(0.713) ng.ml-1 upon reperfusion following 15, 30 and 60 min occlusion, respectively (each p less than 0.05). Maximum increases in epicardial venous blood noradrenaline concentrations during reperfusion were correlated with duration of preceding occlusion (r = 0.60, n = 21, p less than 0.01). Maximum increases in mean arrhythmic ratios observed during the first 10 min of reperfusion were proportionally related to mean epicardial venous blood noradrenaline concentrations. The increases in epicardial venous blood noradrenaline concentrations and the incidence of ventricular arrhythmias in the 60 min occlusion group were greater (p less than 0.05) than in the other two groups.

CONCLUSIONS

This study shows that noradrenaline is released progressively from the ischaemic area during occlusion for 60 min. The amount of noradrenaline washed out upon reperfusion and the incidence of reperfusion ventricular arrhythmias both appear to be dependent upon duration of preceding occlusion. The results suggest that cardiac noradrenaline released locally from the ischaemic region may contribute to the genesis of reperfusion ventricular arrhythmias, but not to that of reperfusion ventricular fibrillation.

摘要

研究目的

本研究旨在探讨再灌注诱导的局部心肌去甲肾上腺素释放增加的闭塞时间依赖性与室性心律失常发生率之间的关系。

设计

将三组犬(每组n = 10)的左冠状动脉前降支分别结扎15、30和60分钟。每个闭塞期后均进行30分钟的再灌注期。将冠状动脉窦和与左冠状动脉前降支并行的心外膜静脉插管,用于测量去甲肾上腺素和乳酸。

实验材料

30只成年杂种犬,体重22.5(标准误1.1)kg,用于本研究。动物用戊巴比妥钠麻醉。

测量与主要结果

在闭塞期间,心外膜静脉血去甲肾上腺素浓度在30分钟内保持不变,但在闭塞60分钟后从0.133(0.027)ng/ml增加至0.289(0.069)ng/ml(p < 0.05)。然而,心外膜静脉血乳酸浓度在闭塞后立即升高,并在所有组的整个闭塞期间保持升高(p < 0.05)。冠状动脉窦血中的去甲肾上腺素和乳酸浓度在闭塞期间均未增加。在再灌注期间,9只犬出现早期心室颤动。颤动发生率最高(n = 5/10)出现在15分钟闭塞组,但各组之间差异不显著。在15、30和60分钟闭塞后的再灌注时,心外膜静脉血去甲肾上腺素浓度分别增加至0.371(0.076)ng/ml、0.470(0.178)ng/ml和1.824(0.713)ng/ml(每组p < 0.05)。再灌注期间心外膜静脉血去甲肾上腺素浓度的最大增加与先前闭塞的持续时间相关(r = 0.60,n = 21,p < 0.01)。再灌注最初10分钟内观察到的平均心律失常比率的最大增加与心外膜静脉血去甲肾上腺素平均浓度成比例相关。60分钟闭塞组的心外膜静脉血去甲肾上腺素浓度增加和室性心律失常发生率均高于其他两组(p < 0.05)。

结论

本研究表明,在60分钟的闭塞期间,去甲肾上腺素从缺血区域逐渐释放。再灌注时洗出的去甲肾上腺素量和再灌注室性心律失常的发生率似乎均取决于先前闭塞的持续时间。结果表明,缺血区域局部释放的心脏去甲肾上腺素可能促成再灌注室性心律失常的发生,但与再灌注心室颤动的发生无关。

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