Novel approach for enhancing atrioventricular nodal conduction delay mediated by endogenous adenosine.
Novel approach for enhancing atrioventricular nodal conduction delay mediated by endogenous adenosine.
复制标题
增强内源性腺苷介导的房室结传导延迟的新方法。
DOI：
10.1161/01.res.75.6.972
复制
发表时间：
1994
影响因子：
20.1
通讯作者：
Belardinelli,L
中科院分区：
文献类型：
--
作者：
Kollias-Baker,C;Xu,J;Pelleg,A;Belardinelli,L
2-氨基-3-苯甲酰基噻吩衍生物PD 81，723可增强外源性腺苷和腺苷受体激动剂在豚鼠离体灌注和原位心脏中A1受体介导的负性传导效应。本研究的目的是确定PD 81，723是否可以放大内源性腺苷的心脏作用。两种已知的增加腺苷心肌间质浓度的方法--缺氧，增加腺苷的产生和腺苷激酶的抑制，减少其代谢--被用来检验这一假设。在豚鼠原位心脏中，PD 81，723（2 mg/kg i. v.）增强低氧血症（PaO 2，14 - 19 mm Hg）引起的房室（AV）结传导延迟。在豚鼠离体心脏中，PD 81，723（5 mumol/L）使5分钟缺氧（2/5%O2/70%N2/5%CO2）和给予腺苷激酶抑制剂iodotubercidin（40 - 70 nmol/L）诱导的刺激-希氏束（S-H）间期延长两倍，但对冠状动脉传导没有影响。缺氧和缺氧加PD 81，723（5 mumol/L）引起心外膜渗出液中腺苷浓度的同等增加，分别从0.13 +/- 0.15增加至0.48 +/- 0.1和0.45 +/- 0.4 mumol/L。与变构增强剂相似，核苷摄取阻断剂draflazine（0.1 mumol/L）也使缺氧引起的S-H间期延长增加两倍。与变构增强剂相反，在缺氧期间，德拉氟嗪将心外膜渗出液中腺苷的浓度从0.48 +/- 0.15增加至1.5 +/- 0.4 mumol/L。在豚鼠常氧恒倍灌注心脏中，Draflazine也使冠状动脉传导增加约2倍。（250字处删节）
The 2-amino-3-benzoylthiophene derivative PD 81,723 potentiates the A1 receptor-mediated negative dromotropic effect of exogenous adenosine and adenosine receptor agonists in guinea pig isolated perfused and in situ hearts. The objective of this study was to determine whether PD 81,723 could amplify the cardiac actions of endogenous adenosine. Two approaches known to increase the myocardial interstitial concentration of adenosine--hypoxia, which increases the production of adenosine and the inhibition of adenosine kinase, which decreases its metabolism--were used to test this hypothesis. In guinea pig hearts in situ, PD 81,723 (2 mg/kg i.v.) potentiated the atrioventricular (AV) nodal conduction delay caused by hypoxemia (PaO2, 14 to 19 mm Hg). In guinea pig isolated hearts, PD 81,723 (5 mumol/L) increased by twofold the stimulus-to-His bundle (S-H) interval prolongations induced by both a 5-minute period of hypoxia (25% O2/70% N2/5% CO2) and the administration of the adenosine kinase inhibitor iodotubercidin (40 to 70 nmol/L) but had no effect on coronary conductance. Hypoxia and hypoxia plus PD 81,723 (5 mumol/L) caused equivalent increases in the concentration of adenosine in epicardial transudate, from 0.13 +/- 0.15 to 0.48 +/- 0.1 and 0.45 +/- 0.4 mumol/L, respectively. Similar to the allosteric enhancer, the nucleoside uptake blocker draflazine (0.1 mumol/L) also increased by twofold the S-H interval prolongation caused by hypoxia. In contrast to the allosteric enhancer, draflazine increased the concentration of adenosine in epicardial transudate during hypoxia from 0.48 +/- 0.15 to 1.5 +/- 0.4 mumol/L. Draflazine also increased coronary conductance by approximately twofold in guinea pig normoxic constant-fold perfused hearts.(ABSTRACT TRUNCATED AT 250 WORDS)