Konishi T, Nakamura Y, Konishi T, Kawai C
Cardiovasc Res. 1984 Oct;18(10):639-44. doi: 10.1093/cvr/18.10.639.
We examined the effects of a clinically relevant concentration (2 X 10(-7) mol . litre-1) of verapamil on the cardiac functions of isolated working rat hearts during global ischaemia (15 min) and reperfusion (30 min). The aorta and the left atrium of each heart of male Sprague-Dawley rats were cannulated for perfusion with Krebs-Henseleit solution, and a soft elastic catheter was introduced into the left ventricle through the left atrial cannula. Verapamil slightly increased the left ventricular end-diastolic pressure, and slightly decreased the left ventricular dP/dt, but did not reduce the left ventricular peak systolic pressure before ischaemia. During the early phase of ischaemia and reperfusion, verapamil (n = 6) lowered the left ventricular peak systolic pressure and the left ventricular dP/dt in comparison with the controls (n = 6) (left ventricular peak systolic pressure 45.4 +/- 16.9 versus 60.9 +/- 15.2 mmHg: p less than 0.05; left ventricular dP/dt 1256 +/- 484 versus 2108 +/- 829 mmHg . s-1: p less than 0.05, after 30 min of reperfusion). Fifteen min of ischaemia resulted in no increase in the creatine kinase release during reperfusion. The creatine kinase release was not different in the two groups during the experiment. Thus, the negative inotropic effect of verapamil was accentuated by the ischaemic intervention. Myocardial protection may be achieved by reducing the left ventricular peak systolic pressure and thereby the oxygen consumption. On the other hand, in clinical application to patients with extensive myocardial ischaemia, verapamil may cause untoward deterioration in cardiac functions.
我们研究了临床相关浓度（2×10⁻⁷摩尔·升⁻¹）的维拉帕米对离体工作大鼠心脏在全心缺血（15分钟）和再灌注（30分钟）期间心脏功能的影响。将雄性Sprague-Dawley大鼠每只心脏的主动脉和左心房插管，用Krebs-Henseleit溶液灌注，并用一根柔软的弹性导管通过左心房插管插入左心室。维拉帕米使左心室舒张末期压力略有升高，左心室dP/dt略有降低，但在缺血前未降低左心室收缩压峰值。在缺血和再灌注早期，与对照组（n = 6）相比，维拉帕米（n = 6）降低了左心室收缩压峰值和左心室dP/dt（再灌注30分钟后，左心室收缩压峰值45.4±16.9对60.9±15.2 mmHg：p＜0.05；左心室dP/dt 1256±484对2108±829 mmHg·s⁻¹：p＜0.05）。15分钟的缺血导致再灌注期间肌酸激酶释放未增加。实验期间两组的肌酸激酶释放无差异。因此，缺血干预增强了维拉帕米的负性肌力作用。通过降低左心室收缩压峰值从而降低耗氧量可能实现心肌保护。另一方面，在广泛心肌缺血患者的临床应用中，维拉帕米可能导致心脏功能不良恶化。
