Noninvasive assessment of the inodilator action of amrinone in healthy man

Summary The effects of a single dose of 2 mg/kg amrinone (60 min constant rate IV infusion) have been assessed in a double-blind, placebo-controlled, within-subject cross-over study in six healthy volunteers. Combined impedance cardiography, phonocardiography and electrocardiography revealed a protracted drop in mean ventricular ejection time and electromechanical systole together, with a protracted rise in the contractility indices dZ/dt_max and the Heather index HI. The profile is compatible with combined venous vasodilation and positive inotropic action. In spite of the methodological constraints, endpoints were reached that were both detectable and relevant. The profiling permitted a better distinction to be made between the possible levels of action than systolic time intervals alone could have done. Therefore, these methods may be of value in the early development of inodilator drugs.     

国产静脉氨力农对充血性心力衰竭疗效观察

本文以双盲对照法,对104例充血性心力衰竭患者应用国产静脉氨力农注射液治疗10天的疗效进行了研究。临床及超声心动图结果均支持该药可改善心功能。治疗组52例中43例心功能改善,对照组52例中5例改善、11例恶化。未发现该药有何不良反应,提示短期静脉注射安全有效。     

HPLC法测定氨力农对照品的色谱纯度

目的建立高效液相色谱法测定氨力农对照品的色谱纯度。方法采用YMC-packODS-AM(5μm,150×6.0mm)色谱柱,以0.1 mol.L-1磷酸钠溶液(磷酸调节pH至6.0)—乙腈(93∶7)为流动相,用DAD检测器320nm波长处测定。结果氨力农主成份与杂质峰能够完全分离,在0.15~1μg.ml-1浓度范围内呈良好的线性天系(r=0.9996),进样精密度为1.83%,最低检测限为0.049μg。结论此法操作简便、快速、准确,可用于测定氨力农对照品的色谱纯度。     

氨吡酮对离体大鼠灌注心脏布比卡因毒性作用的影响

目的　在离体大鼠灌注心脏模型中观察氨吡酮对布比卡因 (BU P)心脏毒性作用的影响。方法　选用 SD大鼠离体心脏 L angendorff灌注模型 ,随机将大鼠心脏分为三组 ,分别为对照组(组 )、输注 Bup 80μg/ min 15 min(组 )、输注 Bup 80μg/ m in 15 min后 ,输注氨吡酮 80μg/ m in 15 min(组 ) ,观察心率 (HR)、左室舒张末期压 (L VEDP)、左室发展压 (L VDP)、 dp/ dt、- dp/ dt的变化以及心肌 c AMP含量。结果　组 、组 在输注 Bup后 HR,L VDP、 dp/ dt、- dp/ dt值与基础值比较均明显降低 ,而 L VEDP则明显高于基础值 ,而组 在输注氨吡酮后上述指标均得以恢复 ,组 心肌c AMP含量也明显低于组 和组 。结论　氨吡酮逆转 Bup心脏毒性作用可能与其增加心肌组织c AMP含量和改善心肌收缩舒张功能有关。     

氨力农对大鼠离体心肌缺血/再灌注损伤的保护作用

目的　氨力农预处理大鼠离体缺血 /再灌注心肌或心肌经历缺血 /再灌注后灌注液加用氨力农 ,观察其有无心肌保护作用。方法　将 3 0只SD大鼠随机平均分对照组 (A组 )、停跳前灌注液加氨力农组 (B组 )和复跳后灌注液加氨力农组 (C组 ) ,应用离体灌注心模型 ,全心 2 5℃停跳3 0min ,再灌注复跳 12 0min ,测定复跳后 10、3 0、60、12 0min左室发展压 (LVDP)恢复率、冠脉流量(CF)恢复率、心肌含水量、心肌细胞ATP含量、心肌超微结构。结果　复跳后C组LVDP恢复率、CF恢复率、心肌含水量、ATP含量、心肌显微结构明显优于A组 (P <0 .0 5 ) ,其CF恢复率优于B组 (P <0 .0 1) ;复跳后 60、12 0minLVDP恢复率B组优于A组 (P <0 .0 5 )。结论　离体大鼠心肌缺血 /再灌注后加用氨力农有明显心肌保护作用 ,氨力农预处理对心肌缺血 /再灌注损伤也有改善作用。     

Effect of amrinone during group B Strepfococcus-induced pulmonary hypertension in piglets

Intravenous infusion of group B Streptococcus (GBS) into neonatal animals pro- duces pulmonary hypertension, ventilation/perfusion (V?_A/Q?) mismatch, and an increase in serum levels of thromboxane B₂, (TxB₂) and tumor necrosis factor (TNF)α. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase inhibitor and is reported to inhibit thromboxane A₂ and TNF production. We hypothesized that infusion of amr would cause pulmonary vasodilation and reduce serum TxB₂, and TNF levels in piglets with late phase GBS-induced pulmonary hypertension. The effect of amr on gas exchange was also determined. A continuous infusion of GBS was administered for 5 hr to 4 groups of anesthetized, mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4 hr followed by a 1 hr continuous infusion of either 10 or 20μg/kg/min of amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr infusion of amr carrier. The infusion of amr, but not of carrier reversed late phase GBS- induced pulmonary hypertension. Piglets infused with amr 20 showed transient selective pulmo- nary vasodilation, based on a reduced ratio of pulmonary to systemic vascular resistance (PVW SVR ratio) value at 30min but not at 1 hr. compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and control group did not change after treatment with either amr or carrier. Treatment with amr 10 or 20 did not decrease serum TxB₂, or TNF levels or increase VA/Q mismatch. A subsequent group of piglets received an 8 mg/kg bolus and 40 μg/kg/min infusion of amr (amr 40) to determine if the increased infusion rate would sustain a selective pulmonary vasodilatory effect beyond 30 min. The PVR/SVR ratio values for amr 40 did not change after treatment for 30 min or 1 hr, compared to pretreatment values. We conclude that amr is effective in reversing GBS-induced pulmonary hypertension. However, the reduction in SVR caused by amr may preclude its use in septic newborns. Pediatr Pulmonol. 1993; 16:303–310. © 1993 Wiley-Liss, Inc.     

A comparison of the effects of three positive inotropic agents (amrinone, milrinone and medorinone) on platelet aggregation in human whole blood

Amrinone, milrinone and medorinone inhibit platelet aggregation in human whole blood. They are particularly potent inhibitors of arachidonic acid induced aggregation, inhibiting by 50% (IC₅₀) at concentrations of 1.5μM (milrinone), 7.5μM (medorinone) and 48μM (amrinone). Each drug was less potent at inhibiting ADP and collagen-induced aggregation. The rank order for inhibition of arachidonic acid - induced aggregation correlated well with the rank order of cyclic AMP phosphodiesterase inhibition for these drugs when coupared to the response of a reference cAMP phosphodiesterase inhibitor (CI-930) and a reference cAMP phosphodiesterase inhibitor (M & B 22948). Since inhibition of platelet aggregation occurred at clinically relevant concentrations, it is evident that these agents have potentially beneficial antithrombotic properties.     

老年左心衰竭患者氨力农治疗时PTFV1动态变化

应用氨力农治疗老年左心衰竭（左心衰）５３例，与洋地黄合用巯甲丙脯酸、硝酸异山梨醇酯、利尿剂５７例作为对照组，观察治疗前后心功能和心电图ＰＴＦＶ１动态变化。结果：治疗一周时氨力农组心功能改善总有效率９６．２％，对照组４３．８％，两组间有非常显著性差异（Ｐ〈０．０１）。治疗后氨力农组与对照组ＰＴＦＶ１〉－０．－３ｍｍ．ｓ分别为８８．７％和４７．４％，ＰＴＦＶ１〈＝－０．０３ｍｍ．ｓ分别为１１．３％和５     

国产氨利酮对血液灌流犬离体窦房结和乳头肌以及麻醉犬的血流动力学效应

本文报道国产氨利酮对血液灌流犬离体窦房结与前乳头肌标本,以及麻醉犬血流动力学和心肌耗氧量的影响,并与进口品作对比。结果表明:国产氨利酮有较强的正变力作用和一定的正变时效应,对麻醉犬有增强心功能但不改变心肌耗氧量的作用。以上各效应与进口品比较无明显差异。     

Elimination of amrinone during continuous veno-venous haemofiltration after cardiac surgery

We studied the elimination of amrinone during continuous veno-venous haemofiltration (CVVHF) in three anuric patients after cardiac surgery. The patients had developed low cardiac output followed by acute prerenal failure. Plasma amrinone levels measured by HPLC were fitted to a two-compartment model.We found significant amrinone clearance, with a mean sieving coefficient (S) of 0.44%, which correlates with the protein-unbound, pharmacologically effective fraction of amrinone. The AUC of the arterial plasma concentration-time curve was decreased by 49.8%. All pharmacokinetic parameters showed wide interindividual variation.To ensure the therapeutic effect of amrinone and to avoid toxic adverse effects monitoring of plasma amrinone levels is necessary.