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奎宁在人体中的抗心律失常活性。

Antiarrhythmic activity of quinine in humans.

作者信息

Sheldon R, Duff H, Koshman M L

机构信息

Cardiovascular Research Group, University of Calgary, Alberta, Canada.

出版信息

Circulation. 1995 Nov 15;92(10):2944-50. doi: 10.1161/01.cir.92.10.2944.

Abstract

BACKGROUND

Quinine is the diastereomer of quinidine. In dogs, it has similar effects on conduction time but does not prolong epicardial repolarization time or ventricular refractoriness. It has antiarrhythmic effects in both cats and dogs. We assessed the antiarrhythmic potential of quinine in suppressing ventricular arrhythmias in humans.

METHODS AND RESULTS

Patients underwent open-label, dose-ranging trials of quinine with daily doses of 600, 1200, and 1800 mg in a twice-daily dosing regimen. In 17 patients with frequent spontaneous ventricular ectopy, oral quinine suppressed arrhythmia in 11 of 12 patients who finished the study and was not tolerated by 4 patients, and 1 patient withdrew from the study. The mean effective daily dosage was 927 mg, the mean effective trough serum level was 11 mumol/L (range, 4 to 17 mumol/L), and the half-life was 20 +/- 7 hours. In a second open-label, dose-ranging trial in 10 patients with inducible ventricular tachycardia and reduced left ventricular systolic function (left ventricular ejection fraction, 35 +/- 16%), quinine suppressed inducibility of ventricular tachycardia in 3 of 10 patients. At a basic pacing cycle length of 500 milliseconds, ventricular effective refractory period was prolonged (279 +/- 21 versus 247 +/- 10 milliseconds, quinine versus drug free, P = .003). In the remaining patients, ventricular tachycardia cycle length was prolonged (373 +/- 48 versus 253 +/- 30 milliseconds, quinine versus drug free, P < .001). The corrected QT interval was not prolonged.

CONCLUSIONS

Quinine is an effective and convenient antiarrhythmic drug for the suppression of ventricular arrhythmias in humans.

摘要

背景

奎宁是奎尼丁的非对映异构体。在犬类中,它对传导时间有类似影响,但不延长心外膜复极时间或心室不应期。它在猫和犬中均有抗心律失常作用。我们评估了奎宁在抑制人类室性心律失常方面的抗心律失常潜力。

方法与结果

患者接受了奎宁的开放标签、剂量范围试验,采用每日两次给药方案,每日剂量分别为600、1200和1800毫克。在17例频发自发性室性早搏患者中,口服奎宁使12例完成研究的患者中的11例心律失常得到抑制,4例患者不耐受,1例患者退出研究。平均有效日剂量为927毫克,平均有效谷血清水平为11微摩尔/升(范围为4至17微摩尔/升),半衰期为20±7小时。在第二项针对10例可诱发室性心动过速且左心室收缩功能降低(左心室射血分数为35±16%)患者的开放标签、剂量范围试验中,奎宁使10例患者中的3例室性心动过速诱发性降低。在基础起搏周期长度为500毫秒时,心室有效不应期延长(奎宁组为279±21毫秒,无药物组为247±10毫秒,P = 0.003)。在其余患者中,室性心动过速周期长度延长(奎宁组为373±48毫秒,无药物组为253±30毫秒,P < 0.001)。校正QT间期未延长。

结论

奎宁是一种有效且方便的抗心律失常药物,可用于抑制人类室性心律失常。

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