静脉注射重组人脑利钠肽对急性心肌梗死伴心力衰竭患者的急性血流动力学效应的研究

Acute hemodynamic effects of intravenous recombinant human brain natriuretic peptide in patients with acute myocardial infarction complicated with heart failure

目的前瞻性对比静脉注射重组人脑利钠肽（rhBNP）与硝酸甘油（NIT）对急性心肌梗死伴心力衰竭（AMI-CDF）患者的急性血流动力学效应及安全性。方法连续住院的42例发病在12～24h的前壁AMI-CDF的患者，随机分为静脉滴注rhBNP组（给予冲击量1．5μg／kg弹丸式静脉注射，随后以0．0075μg·kg^-1·min^-1维持静脉滴注3h，调整剂量0．015～0．030μg·kg^-1·min^-1维持静脉注射21h，然后停药观察6h）和静脉滴注射NIT组（10～100μg／min静脉注射24h，然后停药观察6h），每组21例。比较两组治疗30h内的有创血流动力学参数、尿量、相应血清生化指标和治疗1周内的主要不良心脏事件（MACE）的发生情况。结果rhBNP组和NIT组间及治疗前后中心静脉压（CVP）和收缩压（SBP）无明显变化。rhBNP组治疗30min后心率较基础值显著下降[（95．3±7．4）比（118．0±8．2）次／min，P〈0．05]并维持至停药后6h；NIT组治疗2h后心率才较基础值下降，差异有统计学意义[（92．8±6．8）比（109．2±7．6）次／min，P〈0．05]，而停药3～6h后心率又基本恢复到治疗前水平。rhBNP组治疗30min后肺小动脉契压（PCWP）较基础值下降48．9％[（13．6±6．4）比（26．9±7．5）mmHg（1mm Hg=0．133kPa），P〈0．05]，治疗1h后心脏指数（CI）较基础值升高27．1％[（2．8±0．4）比（2．2±0．3）L·min^-1·m^-1，P〈0．05]；治疗后2h、3h、6h、12h、18h和24h的PCWP、CI仍均较治疗前有显著改善并可保持至停药后6h（P均〈0．05）。NIT组治疗后2h的PCWP亦较治疗前有显著改善[（18．1±6．8）比（25．4±7．5）mmHg，P〈0．05]，但CI在治疗后3h才较治疗前显著改善，且停药6h后，以上两参数即恢复至治疗前水平。两组比较，rhBNP组治疗后30min至2h的PCWP的降低和CI的增加均较NIT组更为显著（P均〈0．05）；此后至治疗24h，两组以上参数渐趋一致；停药6h后rhBNP组的PCWP和CI仍显著优于NIT组（P均〈0．05）。rhBNP组治疗30h内总尿量较NIT组有增多趋势，且rhBNP组血清钾浓度治疗后较治疗前明显升高[（3．4±0．5）比（4．0±0．4）mmol／L，P〈0．05]。本研究未发现与rhBNP相关的症状性低血压及其他严重不良反应。两组治疗1周内的主要心血管事件的发生情况相似。结论对AMI-CDF的患者静脉注射rhBNP较之NIT有着更好的急性血流动力学效应和临床效果，且安全可行。

Objective To compare the acute hemodynamic effects and safety of intravenous injection of recombinant human brain natriuretic peptide （rhBNP） versus intravenous nitroglycerin （NIT） in acute myocardial infarction （AMI） patients with heart failure. Methods On top of standard therapy, 42 consecutive patients who suffered from anterior wall AMI with heart failure [ pulmonary capillary wedge pressure （PCWP） 〉 16 mm Hg] within 12 to 24 hours from the onset of chest pain were randomized into rhBNP group （n =21, 1.5 μg/kg bolus intravenous injection followed by 0. 0075 μg·kg^-1·mn^-1 for the first 3 hours and 0. 015 - 0. 03 μg·kg^-1·mn^-1 infusion for following 21 hours）and NIT group（ n = 21, 10 to 100 p,g/mn intravenous infusion for 24 hours）. The hemedynamic parameters were monitored by SwanGanz catheter at beseline, during drug infusion and 6 hours post infusion withdraw; total urine output was also obtained. The major adverse cardiac events （MACE） were observed up to 1 week after drug infusions. Results Central venous pressure and systolic blood pressure remained unchanged after rhBNP or NIT infusion. Compared to baseline level, PCWP was significantly reduced by 48.9% （P 〈0. 01 ） at 30 minutes after rhBNP infusion and this effect remained up to 6 hours post infusion withdraw; PCWP reduced by 28.7% （P 〈 0.05） at 2 hours after NIT infusion and this effect remained to 6 hours before infusion withdraw. Cardiac index （CI） was increased by 27.1% （P 〈0.05） at 1 hour after rhBNP infusion and remained till 6 hours post infusion withdraw; CI was significantly increased at 3 hour after NIT infusion and this effect disappeared after infusion withdraw. The PCWP and CI values were significantly higher in rhBNP group than that of NIT group at 30 minutes and 2 hours （P 〈 0. 05）. Heart rate was significantly reduced at 30 minutes （95.3 ± 7.4 vs. 118.0 ± 8.2 bpm, P 〈 0. 05） and at 2 hour （92.8 ± 6.8 vs. 109.2 ± 7.6 bpm, P 〈0. 05） in rhBNP and NIT group, respectively and heart rate remained reduced during the whole infusion period in beth groups. The total urine output for 30 hours in rhBNP group （1870 ±535 ml） tended to be higher than that in NIT group （ 1538 ± 620 ml, P 〉 0. 05 ）. There was no symptomatic hypotension or other adverse events during drug infusion in both groups and MACE up to 1 week post drug infusion was also similar between the two groups. Conclusion Intravenous injection of rhBNP results in more rapid and longlasting hemedynamic improvements than that of NIT in AMI patients with heart faihre and it is also feasible and safe for clinic use in AMI patients with heart failure.