Gonschior P, Backfisch G, Muth G, Schiele R, Vogel-Wiens C, Pahl C, Sponer G
Deutsches Herzzentrum und Med.Klinik I, Klinikum rechts der Isar, Lazarettstrasse 36, 80636 Munich, Germany.
J Invasive Cardiol. 1999 Oct;11(10):600-7.
In this experimental series we tested drug distribution and systemic leakage using local drug delivery with a new transvascular injection system.
Porcine femoral and carotid arteries (n = 56) underwent local drug application with a new 5 French (Fr) over-the-wire needle-injection catheter system (NIC) using three needles. A radioactive indicator [C14-Carvedilol, 2.0 milliliter (ml); 0.03 milligram (mg)] was injected in two carotid and two femoral vessels in parallel. Serial blood withdrawal was performed thereafter. After randomization to different explantation times, the vessels, perivascular tissue, liver and spleen were removed [0.5, 1, 1.5, 3 and 4 hours after injection, respectively]. Radioactivity was determined in a scintillation counter or with autoradiography. The indicator amount was calculated in relation to total drug amount (100%).
Use of the NIC caused vessel texture alteration in non-diseased porcine vessels, seen as vessel wall penetration and perivascular edema. After single injection the maximum of the indicator was found in perivascular tissue 0.5 hours at the application site (carotid perivascular tissue: 7.48%; femoral perivascular tissue: 2.56%). Thereafter, radioactivity in the artery increased and perivascular content declined. The maximum in femoral arteries (1 hour; 1.96%) occurred earlier and was significantly lower compared to carotid arteries (2 hours; 7.75%). Four hours post-injection, 1.4% of total drug amount was detectable in the carotid arteries and 0.6% was detected in the femoral arteries. Systemic content was measured after C14-Carvedilol application with a maximum in serum of 28% (10 minutes), liver 30% (0.5 hour) and spleen 0.6% (0.5 hour). After 3 hours, still 5% of the indicator was still measureable in the serum and liver and less than 0.1% was measurable in the spleen. LDD with the NIC system is dependent on the vascular anatomy. The data indicate redistribution from perivascular to vascular space thus allowing a prolonged vascular and perivascular drug delivery. The amount deliverable is lower than expected due to substantial systemic drug contamination with this catheter.
在本系列实验中，我们使用一种新型经血管注射系统进行局部给药，测试药物分布和全身渗漏情况。
使用一种新型的5法国（Fr）的经导丝针注射导管系统（NIC），通过三根针，对猪的股动脉和颈动脉（n = 56）进行局部给药。将放射性指示剂[C14 - 卡维地洛，2.0毫升（ml）；0.03毫克（mg）]并行注射到两根颈动脉和两根股血管中。此后进行连续采血。随机分配到不同的取材时间后，分别在注射后0.5、1、1.5、3和4小时取出血管、血管周围组织、肝脏和脾脏。通过闪烁计数器或放射自显影测定放射性。根据总药量（100%）计算指示剂的量。
使用NIC导致未患病猪血管的血管纹理改变，表现为血管壁穿透和血管周围水肿。单次注射后，在给药部位血管周围组织0.5小时时发现指示剂含量最高（颈动脉血管周围组织：7.48%；股动脉血管周围组织：2.56%）。此后，动脉中的放射性增加，血管周围的含量下降。股动脉中含量最高时（1小时；1.96%）出现得更早，且与颈动脉（2小时；7.75%）相比显著更低。注射后4小时，在颈动脉中可检测到总药量的1.4%，在股动脉中检测到0.6%。在应用C14 - 卡维地洛后测量全身含量，血清中最高含量为28%（10分钟），肝脏中为30%（0.5小时），脾脏中为0.6%（0.5小时）。3小时后，血清和肝脏中仍有5%的指示剂可测量，脾脏中可测量的不到0.1%。使用NIC系统进行局部给药取决于血管解剖结构。数据表明从血管周围向血管腔的再分布，从而实现血管和血管周围药物的延长递送。由于该导管存在大量全身药物污染，可递送的药量低于预期。
