Arh M, Budihna M V
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, Ljubljana, Slovenia.
Pflugers Arch. 2000;440(5 Suppl):R149-50.
During ischaemia and reperfusion increased cytosolic Ca2+ is one of the important causes for ischaemic-reperfusion myocardial injury. In the present study we compared effects of preferentially L-type Ca2+ antagonists nitrendipine (NT) and lacidipine (LP), and of mibefradil (MB) a Ca2+ antagonist with higher affinity to T- than to L-type channels on myocardial function during reperfusion. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), lactate dehydrogenase (LDH) release rate and ECG were registered during 40 min of reperfusion following 30 min of global zero flow ischaemia in Langendorff's isolated rat hearts. Either NT (100 nmol/L) or LP (10 nmol/L) or MB (100 nmol/L) was added to Krebs-Henseleit solution 10 min before ischaemia till the end of experiments. All three drugs influenced CF, HR and LVP. All of them decreased LDH release rate (P < 0.05, in microkat/g x min) when compared with control hearts (53.2 +/- 5.1): MB (19.4 +/- 4.3) > LP (30.7 +/- 6.6) > NT (43.3 +/- 2.8). NT reduced the duration of continuous arrhythmias at the beginning of reperfusion (to 59.1 +/- 6.1% of ischaemic controls) as well as the number of single arrhythmic events arising during the whole period of reperfusion (to 26.1 +/- 6.0% of ischaemic controls). MB diminished only single arrhythmic events during reperfusion to 39.1 +/- 17.3% of ischaemic controls. LP did not affect the onset of arrhythmias. Results of our experiments indicate a relatively greater importance of T-type than of L-type Ca2+ channels in the arising of postischaemic myocardial damage.
在缺血和再灌注过程中，胞质Ca2+增加是缺血-再灌注心肌损伤的重要原因之一。在本研究中，我们比较了优先作用于L型Ca2+通道的拮抗剂尼群地平（NT）和拉西地平（LP），以及对T型通道亲和力高于L型通道的Ca2+拮抗剂米贝拉地尔（MB）在再灌注期间对心肌功能的影响。在Langendorff离体大鼠心脏进行30分钟全心零流量缺血后再灌注40分钟期间，记录冠状动脉血流量（CF）、心率（HR）、左心室压力（LVP）、乳酸脱氢酶（LDH）释放率和心电图。在缺血前10分钟至实验结束，将NT（100 nmol/L）或LP（10 nmol/L）或MB（100 nmol/L）添加到Krebs-Henseleit溶液中。所有三种药物均影响CF、HR和LVP。与对照心脏（53.2±5.1）相比，它们均降低了LDH释放率（P<0.05，微卡/克×分钟）：MB（19.4±4.3）>LP（30.7±6.6）>NT（43.3±2.8）。NT减少了再灌注开始时持续性心律失常的持续时间（降至缺血对照组的59.1±6.1%）以及整个再灌注期间出现的单个心律失常事件的数量（降至缺血对照组的26.1±6.0%）。MB仅将再灌注期间的单个心律失常事件减少至缺血对照组的39.1±17.3%。LP不影响心律失常的发生。我们的实验结果表明，T型Ca2+通道在缺血后心肌损伤的发生中比L型Ca2+通道相对更重要。
