Kocić I, Konstański Z, Kaminski M, Dworakowska D, Dworakowski R
Department of Pharmacology, Medical University of Gdańsk, Poland.
Gen Pharmacol. 1999 Sep;33(3):213-9. doi: 10.1016/s0306-3623(99)00017-8.
This study was designed to establish a hyperlipidemic diet (significant increase in the cholesterol and triglycerides blood levels, but without atherogenic changes in heart muscle and coronary vessels) and to investigate the influence of experimental hyperlipidemia on the effects of ischemic preconditioning (PC) of rat-isolated papillary muscle on the time course of contractility during simulated ischemia and reperfusion and responsiveness to phenylephrine under such a condition. The animals were divided in four experimental groups: standard diet-fed control group (SD), SD underwent ischemic preconditioning (SD-PC), hyperlipidemic diet-fed group (HLD) and HLD underOFFt PC (HLD-PC). Force of contraction (Fc), velocity of contraction (+dF/dt), and velocity of relaxation (-dF/dt) were measured. HLD preparations were more sensitive to ischemia then SD ones. PC, performed by 5-min perfusion with no-substrate solution gassing with 95% N2/5% CO2 in the presence of fast electrical stimulation, and 10 min of reperfusion with normal solution and rate of stimulation, significantly increased the resistance of isolated cardiac tissues to simulated ischemia in SD-PC group, but not in HLD-PC group. Negative inotropic action of phenylephrine occured in SD group of preparations after simulated-ischemia/reperfusion period was also prevented by PC. Therefore, we conclude that experimental hyperlipidemia significantly influenced the function of rat heart muscle including the higher sensitivity to ischemia and different reaction to the same PC procedure.
本研究旨在建立一种高脂血症饮食(显著提高血液中胆固醇和甘油三酯水平,但心肌和冠状血管无动脉粥样硬化改变),并研究实验性高脂血症对大鼠离体乳头肌缺血预处理(PC)在模拟缺血和再灌注期间收缩力时间进程以及在此条件下对去氧肾上腺素反应性的影响。将动物分为四个实验组:标准饮食喂养对照组(SD)、接受缺血预处理的SD组(SD-PC)、高脂血症饮食喂养组(HLD)和接受PC的HLD组(HLD-PC)。测量收缩力(Fc)、收缩速度(+dF/dt)和舒张速度(-dF/dt)。HLD组的制剂对缺血比SD组更敏感。在快速电刺激下,用95%N2/5%CO2通气的无底物溶液灌注5分钟,然后用正常溶液和刺激频率再灌注10分钟进行PC,在SD-PC组中显著增加了离体心脏组织对模拟缺血的耐受性,但在HLD-PC组中未增加。在模拟缺血/再灌注期后,SD组制剂中去氧肾上腺素的负性肌力作用也被PC所阻止。因此,我们得出结论,实验性高脂血症显著影响大鼠心肌功能,包括对缺血的更高敏感性以及对相同PC程序的不同反应。