Preservation of high-energy phosphates by verapamil in reperfused myocardium.
Preservation of high-energy phosphates by verapamil in reperfused myocardium.
复制标题
维拉帕米在再灌注心肌中保存高能磷酸盐。
作者：
R. Lange;J. Ingwall;S. Hale;K. Alker;E. Braunwald;R. Kloner
为了确定维拉帕米是否能防止严重心肌缺血期间和之后腺嘌呤核苷酸的消耗，我们对狗进行了15分钟的左冠状动脉前降支闭塞，然后再灌注240分钟。闭塞前1小时，随机分为治疗组（n = 10）和生理盐水组（n = 9），治疗组静脉滴注维拉帕米直至再灌注开始。维拉帕米降低平均主动脉压和心率。缺血15 min后，针刺活检检测的心内膜三磷酸腺苷（ATP）水平在未治疗组由34.7 +/- 2.0降至24.4 +/- 2.7 nmol X mg蛋白-1 （p < 0.05）。维拉帕米组从32.8 +/- 1.5到30.3 +/- 1.5 nmol X mg蛋白-1 （NS与牙合前）。再灌注90 min和240 min后，维拉帕米治疗犬的ATP水平明显高于未治疗犬。在未治疗的动物中，肌苷和次黄嘌呤水平的总和在闭塞期间从非常低的水平增加到心外膜的4.6 +/- 1.1 nmol X mg protein-1和心内膜的6.8 +/- 1.5 nmol X mg protein-1 （p < 0.05）。0.05与牙合前值比较)。维拉帕米处理犬的肌苷和次黄嘌呤水平仅升高至1.2 +/- 0.3（心外膜）和1.9 +/- 0.6 nmol X mg蛋白-1（心内膜）（两者均与闭塞前值相比）。再灌注90 min后，未治疗组心内膜中ATP、二磷酸腺苷、单磷酸腺苷、肌苷和次黄嘌呤的含量均降低10.2 nmol X mg protein-1，而维拉帕米治疗组未见变化。我们得出结论，维拉帕米减少了严重缺血时ATP分解为肌苷和次黄嘌呤，导致缺血和再灌注时ATP浓度升高，再灌注时弥漫性嘌呤肌苷和次黄嘌呤的冲洗减少。
To determine whether verapamil prevents depletion of adenine nucleotides during and after severe myocardial ischemia, dogs were subjected to 15 min occlusions of the left anterior descending coronary artery followed by 240 min of reperfusion. One hour before occlusion, dogs were randomly assigned to a treatment group (n = 10) to which an infusion of intravenous verapamil was given until the onset of reperfusion or to an untreated saline group (n = 9). Verapamil reduced mean aortic pressure and heart rate. After 15 min of ischemia, endocardial adenosine triphosphate (ATP) level, determined by needle biopsy, decreased in the untreated group from 34.7 +/- 2.0 to 24.4 +/- 2.7 nmol X mg protein-1 (p less than .005 vs preocclusion) and in the verapamil group from 32.8 +/- 1.5 to 30.3 +/- 1.5 nmol X mg protein-1 (NS vs preocclusion). Dogs receiving verapamil had significantly higher ATP levels than untreated animals after 90 and 240 min of reperfusion. In untreated animals the sum of inosine and hypoxanthine levels increased during occlusion from very low levels to 4.6 +/- 1.1 nmol X mg protein-1 in the epicardium and to 6.8 +/- 1.5 nmol X mg protein-1 in the endocardium (p less than .05 compared with preocclusion values). In verapamil-treated dogs inosine and hypoxanthine levels increased to only 1.2 +/- 0.3 (epicardium) and 1.9 +/- 0.6 nmol X mg protein-1 (endocardium) (both NS compared with preocclusion values). After 90 min of reperfusion the sum of ATP, adenosine diphosphate, adenosine monophosphate, inosine, and hypoxanthine levels was decreased in the endocardium by 10.2 nmol X mg protein-1 in the untreated group, but no change was observed in verapamil-treated animals. We conclude that breakdown of ATP to inosine and hypoxanthine during severe ischemia is reduced by verapamil, resulting in higher ATP concentrations during occlusion and reperfusion and decreased washout of the diffusible purines inosine and hypoxanthine during reperfusion.
犬可逆性心肌缺血损伤后，由于腺嘌呤核苷酸的再合成延迟，导致 ATP 和腺嘌呤核苷酸库的长期消耗。
影响因子：
5
作者：
Reimer,KA;Hill,ML;Jennings,RB
通讯作者：
Jennings,RB
使用嘌呤从头合成的前体加速犬缺血后心肌中 ATP 和 GTP 库的补充。
影响因子：
20.1
作者：
Swain,JL;Hines,JJ;Sabina,RL;Holmes,EW
通讯作者：
Holmes,EW