Beneficial effects of felodipine on myocardial and coronary function during low-flow ischemia and reperfusion.
Beneficial effects of felodipine on myocardial and coronary function during low-flow ischemia and reperfusion.
复制标题
非洛地平对低流量缺血和再灌注期间心肌和冠状动脉功能的有益作用。
DOI：
10.1007/bf00823595
复制
发表时间：
1996
影响因子：
3.4
通讯作者：
Apstein,CS
中科院分区：
文献类型：
--
作者：
Bernstein,EA;Eberli,FR;Silverman,AM;Horowitz,GL;Apstein,CS
急性冠状动脉闭塞导致闭塞区域严重的低血流缺血。钙拮抗剂有可能通过降低心肌需氧量以及其他机制降低缺血性损伤的发生率，尤其是在缺血发作前给药时。然而，它们的临床应用可能受到其负性肌力作用的限制。本研究的目的是评估非洛地平作为一种潜在的心肌缺血和再灌注损伤保护剂，在低流量缺血发生后给药时，与任何负性肌力作用无关的作用。以恒定心率起搏的离体等容（LV内球囊）血液灌注兔心脏在10 mmHg冠状动脉灌注压下进行90分钟的低流量缺血，使冠状动脉血流量降至基线的22-24%。低流量缺血15分钟后，心脏接受2 × 10- 6 M非洛地平（n=7）或无药物（对照组，n=8）。给予非洛地平直至再灌注15分钟。在低流量缺血期间，两组心脏具有相同的冠状动脉血流量、心率、左心室（LV）发展压力、乳酸产生和O2消耗。然而，非洛地平显着保护缺血性舒张功能障碍。低流量缺血结束时，非洛地平组左室舒张末期压（LVEDP）由10±1 mmHg增加到28±5 mmHg，而对照组LVEDP增加到48±8 mmHg（p<0.05）。在30分钟的再灌注过程中，非洛地平对冠状动脉血流量有有益的影响（非洛地平组初始缺血后充血为基线的245±38%，对照组为124±18%;非洛地平明显改善收缩功能的恢复[左室收缩压由104±4 mmHg恢复至75±6 mmHg（72%）]非洛地平组与对照组中的34±10 mmHg（32%）; p<0.01]，以及舒张功能（非洛地平组中的LVEDP=25±4 mmHg与对照组中的61±10 mmHg; p<0.05）和ATP水平（8.5±1.4 μ mol/g d.w.非洛地平组为3.9±1.4 μ mol/g d.w.对照组P<0.05）。非洛地平在低血流缺血发作后给药，通过降低心肌需氧量以外的机制在缺血和再灌注期间保护心肌。
An acute coronary occlusion causes severe lowflow ischemia in the occluded region. Calcium antagonists have the potential to reduce the rate of ischemic injury by decreasing myocardial oxygen demand, as well as by other mechanisms, especially when given prior to the onset of ischemia. However, their clinical use may be limited by their negative inotropic effects. The purpose of this study was to assess the effects of felodipine as a potentially protective agent against myocardial ischemia and reperfusion injury, independent of any negative inotropic actions, when given after the onset of low-flow ischemia. Isolated isovolumic (balloon-in-LV), blood-perfused rabbit hearts, paced at a constant heart rate, were subjected to 90 minutes of low-flow ischemia at a coronary perfusion pressure of 10 mmHg, which reduced coronary blood flow to 22–24% of baseline. After 15 minutes of low-flow ischemia, hearts received 2 × 10-6M felodipine (n=7) or no drug (controls, n=8). Felodipine was given until 15 minutes of reperfusion. During lowflow ischemia both groups of hearts had identical coronary blood flow, heart rate, left ventricular (LV) developed pressure, lactate production, and O2consumption. However, felo-dipine markedly protected against ischemic diastolic dysfunction. At the end of low-flow ischemia, LV end-diastolic pressure (LVEDP) had increased from 10±1 to 28±5 mmHg in the felodipine group, while in the controls LVEDP increased to 48±8 mmHg (p<0.05). During 30 minutes of reperfusion, felodipine had a beneficial effect upon coronary blood flow (initial postischemic hyperemia 245±38% of baseline in the felodipine group vs. 124±18% in the controls; p<0.01) Felodipine markedly improved the recovery of contractile function [LV developed pressure recovered from a baseline of 104±4 to 75±6 mmHg (72%) in the felodipine group vs. 34±10 mmHg (32%) in the control group; p<0.01], as well as diastolic function (LVEDP=25±4 mmHg in the felodipine group vs. 61±10 mmHg in the controls; p<0.05), and ATP levels (8.5±1.4 μmoles/g d.w. in the felodipine group vs. 3.9±1.4 μmoles/g d.w. in the control group, p<0.05). Felodipine, given after the onset of low-flow ischemia, protects the myocardium during both ischemia and reperfusion by mechanisms other than reducing myocardial oxygen demand.