Alousi A A, Canter J M, Fort D J
Cardiovasc Res. 1985 Aug;19(8):483-94. doi: 10.1093/cvr/19.8.483.
Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value.
氨力农是一种具有正性肌力和血管扩张作用的药物，将其给予麻醉犬，试图逆转由具有负性肌力特性的药物所诱发的心力衰竭。普萘洛尔是一种β肾上腺素能阻滞剂；维拉帕米是一种钙慢通道阻滞剂；普鲁卡因胺是一种Ⅰ类抗心律失常药；戊巴比妥钠是一种巴比妥酸盐，通过大剂量注射和/或输注给药后，可使犬的心功能持续受到抑制。心功能抑制的特征为心脏收缩力（CF）和左心室压力最大上升速率（LV dp/dtmax）降低超过40%，心输出量（CO）降低30%至50%，同时平均中心静脉压或平均右心房压（分别为CVP、RAP）升高。氨力农静脉注射大剂量（1或3mg·kg⁻¹）加输注（0.03或0.1mg·kg⁻¹·min⁻¹）给药时，在所有四种药物诱发的心力衰竭模型中，通过增加CF、CO和LV dp/dtmax以及降低前负荷CVP或RAP，逆转了心功能抑制。由于氨力农具有血管扩张特性，在维拉帕米和普鲁卡因胺诱发的心力衰竭以及普萘洛尔诱发的心力衰竭（唯一TPR升高的模型）中，后负荷即总外周阻力（TPR）降低。在另一种心力衰竭模型中，在洋地黄毒苷诱发的心律失常先于普鲁卡因胺毒性出现的情况下，氨力农也是一种有效的强心剂。在普萘洛尔诱发的心力衰竭中研究了洋地黄毒苷的正性肌力作用。虽然观察到LV dp/dtmax升高和CVP降低，但洋地黄毒苷（40μg·kg⁻¹静脉注射）使TPR升高，对CF和CO的抑制作用影响不大。药物诱发的心力衰竭模型是评估强心剂克服严重心功能抑制能力的有用药理学工具。在普萘洛尔、维拉帕米、普鲁卡因胺和戊巴比妥钠诱发的心脏毒性中，氨力农可能具有治疗价值。
