Iberti T J, Weiner B, Stein J S, Premus G, Benjamin E
Crit Care Med. 1985 Feb;13(2):105-8. doi: 10.1097/00003246-198502000-00011.
The use of the calcium channel-blocking agent, verapamil, in beta-blocked patients has been the subject of intense investigation, particularly because both verapamil and the beta-blockers can produce negative inotropic effects. We studied the hemodynamic effects of verapamil in beta-blocked dogs to establish specific measurements that could be used clinically for early identification of combined negative inotropism. Seven anesthetized, mongrel dogs were beta-blocked with propranolol, and then given 2.5-, 5.0-, and 10.0-mg iv boluses of verapamil. The 2.5- and 5.0-mg boluses represent clinical doses, whereas the 10.0-mg bolus is a large pharmacologic dose. Hemodynamic measurements showed that verapamil was well tolerated at clinical doses; increases in stroke volume compensated for decreases in mean arterial pressure. At high doses of verapamil this response was not observed and left ventricular stroke work decreased. Cardiac and stroke indices were not useful indicators of combined drug toxicity in this dog model.
在已使用β受体阻滞剂的患者中使用钙通道阻滞剂维拉帕米一直是深入研究的课题,特别是因为维拉帕米和β受体阻滞剂都可产生负性肌力作用。我们研究了维拉帕米对使用β受体阻滞剂的犬类的血流动力学影响,以确定可在临床上用于早期识别联合负性肌力作用的具体测量指标。七只麻醉的杂种犬先用普萘洛尔进行β受体阻滞,然后静脉注射2.5毫克、5.0毫克和10.0毫克的维拉帕米 bolus。2.5毫克和5.0毫克的bolus代表临床剂量,而10.0毫克的bolus是大的药理剂量。血流动力学测量表明,维拉帕米在临床剂量下耐受性良好;每搏量增加可补偿平均动脉压的降低。在高剂量维拉帕米时未观察到这种反应,左心室每搏功降低。在这个犬类模型中,心脏指数和每搏指数不是联合药物毒性的有用指标。