Tillmanns H, Neumann F J, Parekh N, Waas W, Möller P, Zimmermann R, Steinhausen M, Köbler W
Department of Internal Medicine-Cardiology, University of Giessen, Federal Republic of Germany.
Drugs. 1991;42 Suppl 1:1-6. doi: 10.2165/00003495-199100421-00003.
Recent studies have improved our understanding of the beneficial actions of calcium antagonists on myocardial microcirculation and metabolism. The effect of calcium antagonists on the microcirculation of the left ventricular rat myocardium was studied using in vivo microscopic techniques. Intravenous verapamil 0.3 mg/kg and nifedipine 75 micrograms/kg produced a 15 to 18% increase in the diameter of larger A1 and A2 coronary arterioles (range 31 to 300 microns); diameters of terminal (A4) arterioles and capillaries did not change significantly. Furthermore, verapamil significantly (p less than 0.001) increased the ratio of capillaries filled with red cells to those containing plasma alone. Verapamil pretreatment produced a similarly selective dilatation of larger coronary arterioles and protected against the ischaemia-induced fall in capillary red cell content. Spectroscopic data show that verapamil also produces an increase in myocardial phosphocreatine and preservation of adenosine triphosphate (ATP) during ischaemia in the Langendorff-perfused heart. In patients with exercise-induced angina, gallopamil decreased global myocardial 201Tl and 123I phenylpentadecanoic acid (IPPA) uptake due to a reduction in myocardial oxygen consumption. Regional 201Tl and IPPA uptake as well as IPPA clearance in post-stenotic areas tended to rise after gallopamil treatment. Thus, the beneficial effects of calcium antagonists such as verapamil or gallopamil in patients with ischaemic heart disease may result from dilatation of predominantly larger arterioles. Consequently, there is an improvement in regional perfusion and free fatty acid utilisation in reversibly ischaemic regions.
近期的研究增进了我们对钙拮抗剂在心肌微循环和代谢方面有益作用的理解。运用体内显微技术研究了钙拮抗剂对大鼠左心室心肌微循环的影响。静脉注射维拉帕米0.3毫克/千克和硝苯地平75微克/千克，可使较大的A1和A2冠状动脉小动脉（直径范围为31至300微米）直径增加15%至18%；终末（A4）小动脉和毛细血管的直径无显著变化。此外，维拉帕米显著（p小于0.001）增加了充满红细胞的毛细血管与仅含血浆的毛细血管的比例。维拉帕米预处理同样能选择性地扩张较大的冠状动脉小动脉，并防止缺血引起的毛细血管红细胞含量下降。光谱数据显示，在Langendorff灌注心脏的缺血过程中，维拉帕米还能使心肌磷酸肌酸增加，并保存三磷酸腺苷（ATP）。在运动诱发心绞痛的患者中，加洛帕米可降低整体心肌对201铊和123碘苯基十五烷酸（IPPA）的摄取，原因是心肌耗氧量减少。加洛帕米治疗后，狭窄后区域的局部201铊和IPPA摄取以及IPPA清除率趋于升高。因此，维拉帕米或加洛帕米等钙拮抗剂对缺血性心脏病患者的有益作用可能源于主要对较大小动脉的扩张。结果，可逆性缺血区域的局部灌注和游离脂肪酸利用得到改善。
