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L-肉碱丙酰酯在“体内”人类缺血再灌注模型中保护组织免受缺血性损伤。

L-propionyl-carnitine protects tissues from ischaemic injury in an 'in vivo' human ischaemia-reperfusion model.

机构信息

Angiology Care Unit, University Hospital, Padua, Italy,

出版信息

Clin Drug Investig. 2002 Nov;22(Suppl 1):15-21. doi: 10.2165/00044011-200222001-00003.

DOI:10.2165/00044011-200222001-00003
PMID:23315431
Abstract

OBJECTIVE

To assess the acute effects of L-propionyl-carnitine (LPC) on vaso-motion, tissue perfusion and tissue acidosis during an ischaemia-reperfusion test in patients with intermittent claudication.

DESIGN

Open pharmacodynamic study.

STUDY PARTICIPANTS

Sixteen male patients with intermittent claudication (mean absolute claudication distance 193.19 ± 51.51m).

INTERVENTIONS

Intravenous infusion of LPC 600mg.

MAIN OUTCOME MEASURES AND RESULTS

Laser-Doppler perfusion units and power spectrum, transcutaneous oxygen pressure (TcPO(2)) and transcutaneous carbon dioxide pressure (TcPCO(2)) were measured at baseline, during ischaemia (which was induced by means of an inflated pneumatic cuff wrapped around the calf) and during reperfusion, before and after LPC infusion. Perfusion units and TcPO(2) did not change significantly after LPC infusion compared with pretreatment values. Conversely, mean laser-Doppler power spectrum, which was 0.20 units at rest and 1.13 during reperfusion before treatment, increased significantly to 0.89 and 2.24, respectively, after LPC infusion (p = 0.01 and p = 0.00074, respectively, vs pretreatment values). LPC had no significant effects on resting TcPCO(2), but induced a significant decrease in TcPCO(2) measured at hypoxia point (96.9mm Hg before treatmentvs 90.2mm Hg after treatment; p = 0.001) and during reperfusion (115.9vs 103.5mm Hg, respectively; p = 0.0006).

CONCLUSIONS

These results show that LPC protects tissues from ischaemic injury by improving arteriolar function and reducing acidosis, without affecting arterial inflow. This may explain the beneficial effects of LPC in patients with intermittent claudication and suggests a potential use of this drug in other stages of peripheral arterial disease and in patients undergoing surgery.

摘要

目的

评估 L-丙酰肉碱(LPC)对间歇性跛行患者缺血再灌注试验中血管运动、组织灌注和组织酸中毒的急性影响。

设计

开放药效学研究。

研究对象

16 名男性间歇性跛行患者(平均绝对跛行距离 193.19±51.51m)。

干预

静脉输注 LPC 600mg。

主要观察指标及结果

在基线、缺血(通过在小腿周围包裹充气的气压袖带引起)和再灌注期间,测量激光多普勒灌注单位和功率谱、经皮氧分压(TcPO2)和经皮二氧化碳分压(TcPCO2),并在 LPC 输注前后进行测量。与预处理值相比,LPC 输注后灌注单位和 TcPO2 无显著变化。相反,治疗前静息时平均激光多普勒功率谱为 0.20 单位,再灌注时为 1.13 单位,LPC 输注后分别显著增加至 0.89 和 2.24(p=0.01 和 p=0.00074,分别与预处理值相比)。LPC 对静息 TcPCO2 无显著影响,但可降低缺氧点(治疗前 96.9mmHg 与治疗后 90.2mmHg;p=0.001)和再灌注期间(分别为 115.9mmHg 与 103.5mmHg;p=0.0006)的 TcPCO2。

结论

这些结果表明,LPC 通过改善小动脉功能和减少酸中毒来保护组织免受缺血性损伤,而不影响动脉流入。这可能解释了 LPC 对间歇性跛行患者的有益作用,并提示该药可能在周围动脉疾病的其他阶段以及手术患者中使用。

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