Hugtenburg J G, Mathy M J, Veldsema-Currie R D, Boddeke H W, Beckeringh J J, van Zwieten P A
Department of Pharmacotherapy/Pharmacology, Faculty of Medicine, Academie Medical Center, University of Amsterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jul;340(1):126-34. doi: 10.1007/BF00169218.
The cardioprotective effects of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and the coronary vasodilator dipyridamole were evaluated in the guinea-pig working heart with respect to cardiac function and high energy phosphate content after 45 min of global ischaemia and 25 min of reperfusion. All drugs, with the exception of dipyridamole, induced a negative inotropic effect, which resulted in a decrease of the aortic pressure (AoP), of its first derivative dAoP/dt and the cardiac output. To compare the anti-ischaemic effect of the calcium antagonists, concentrations were selected that reduced the dAoP/dt by 10% (EC10) and 30% (EC30), respectively. With the exception of nifedipine at the EC10 and bepridil and CERM 11956 at the EC30, perfusion with the calcium antagonists and dipyridamole (3 mumol/l) improved the recovery of contractile function after global ischaemia and reperfusion to a value between 60 and 80% of the controls in normoxic hearts. Pretreatment with nifedipine, verapamil, diltiazem, lidoflazine and mioflazine, but not with bepridil, CERM 11956 and dipyridamole led to slightly increased ATP levels in ischaemic hearts as compared to the control value in ischaemic hearts. After subsequent reperfusion for 25 min, for all drugs, ATP levels were further enhanced to 50% of the level in normoxic hearts; phosphocreatine levels reached normoxic values. In particular at the EC30, the effects of calcium antagonists on cardiac function varied in accordance with their known pharmacological and physiological profile. However, there appeared to exist no direct relationship between their beneficial effects on contractile activity and those on the levels of high energy phosphates after ischaemia and reperfusion.
在豚鼠工作心脏模型中，评估了硝苯地平、维拉帕米、地尔硫䓬、苄普地尔、CERM 11956、利多氟嗪、米奥氟嗪以及冠状动脉扩张剂双嘧达莫在45分钟全心缺血和25分钟再灌注后对心脏功能和高能磷酸盐含量的心脏保护作用。除双嘧达莫外，所有药物均诱导负性肌力作用，导致主动脉压（AoP）、其一阶导数dAoP/dt和心输出量降低。为比较钙拮抗剂的抗缺血作用，分别选择使dAoP/dt降低10%（EC10）和30%（EC30）的浓度。除硝苯地平在EC10浓度、苄普地尔和CERM 11956在EC30浓度外，用钙拮抗剂和双嘧达莫（3μmol/l）灌注可使全心缺血和再灌注后收缩功能的恢复提高到常氧心脏对照组值的60%至80%。与缺血心脏的对照值相比，硝苯地平、维拉帕米、地尔硫䓬、利多氟嗪和米奥氟嗪预处理可使缺血心脏的ATP水平略有升高，但苄普地尔、CERM 11956和双嘧达莫预处理则无此作用。随后再灌注25分钟后，所有药物的ATP水平进一步升高至常氧心脏水平的50%；磷酸肌酸水平达到常氧值。特别是在EC30浓度时，钙拮抗剂对心脏功能的影响与其已知的药理和生理特性相符。然而，它们对缺血和再灌注后收缩活动的有益作用与对高能磷酸盐水平的有益作用之间似乎不存在直接关系。
