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本研究利用有意识的清醒犬模拟急性左心衰竭加重的患者在急性和慢性静脉内给药后,其静脉扩张剂脉导(molsidomine)的活性代谢产物SIN-1的血液动力学效应。通过诱导血管计测量区域静脉电容变化,在氯醛糖麻醉期间研究对静脉的直接影响并分析左心室功能。将SIN-1诱导效应的动力学与硝酸甘油和硝酸异山梨酯诱导的效应进行比较。研究结果表明:平均推注剂量为2 mg SIN-1后,平均右心房压(MRAP)、平均肺动脉压(MPAP)和肺毛细血管楔压(PCAP)显著下降至第60分钟;肺血管阻力(PVR)显著下降至第30分钟,而心脏指数(CI)和全身血管阻力(SVR)保持不变。在连续24 h输注SIN-1期间,MRAP、MPAP和PCAP显著下降,而CI、PVR和SVR基本保持不变。在24 h内不需要剂量调整来维持血液动力学效应。在SIN-1诱导静脉汇集期间,未检测到对冠状动脉循环的任何直接影响或药物的任何直接心脏抑制活性。在长期给药期间没有值得注意的副作用和耐受性。本研究初步表明SIN-1是对治疗急性左心衰竭加重的患者有一定的缓解作用,但不能持续使用的潜在药物。
Abstract：To use the conscious awake dogs to simulate the hemodynamic effects of the active metabolite SIN-1 of the venous dilating agent molsidomine in patients with acute left heart failure after acute and chronic intravenous administration. The changes of regional venous capacitance were measured by inducing vasculometer,and the direct effects on veins were studied during chloraldose anesthesia and left ventricular function was analyzed. The kinetics of the SIN-1 induction effect was compared to that induced by nitroglycerin and isosorbide dinitrate. Mean right atrial pressure(MRAP), mean pulmonary arterial pressure(MPAP), and pulmonary capillary wedge pressure(PCAP) decreased significantly to the 60 th minute after an average bolus dose of 2 mg SIN-1;pulmonary vascular resistance(PVR)) Significantly dropped to the 30 th minute, while the heart index(CI) and systemic vascular resistance(SVR) remained unchanged. During the continuous 24 hour infusion of SIN-1, MRAP,MPAP and PCAP decreased significantly, while CI, PVR and SVR remained essentially unchanged. No dose adjustment is required within 24 hours to maintain the hemodynamic effect. No direct effects on coronary circulation or any direct cardiostatic activity of the drug were detected during SIN-1 induced venous collection.There were no notable side effects and tolerability during long-term administration; this research suggested that SIN-1 should be a potential drug for the treatment of patients with conscious conscious dogs that mimic the exacerbation of acute left heart failure, but cannot be used continuously.
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基本信息:
DOI：10.13417/j.gab.038.004660
中图分类号:R541.6
引用信息:
[1]朱小琴,夏清德,师燕花,等.SIN-1在急性左心衰竭中的血流动力学效应的作用机制[J].基因组学与应用生物学,2019,38(10):4660-4667.DOI:10.13417/j.gab.038.004660.
2019-10-25
2019-10-25