TECHNICAL NOTES

Catheterization of the Hepatic Artery Via the LeftCommon Carotid Artery in Rats

Xiao Li,1 Yi-Xiang J. Wang,2* Xiangping Zhou,1 Yongsong Guan,3

Chengwei Tang3

1Department of Radiology, West China Hospital, Sichuan University, Chengdu, People�s Republic of China2Department of Radiology, Rui Jin Hospital, Shanghai Second Medical University, Shanghai, People�s Republic of China3Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, People�s Republic of China

Abstract

The commonly used approach for rat hepatic artery cathe-terization is via the gastroduodenal artery, which is ligatedafter the procedure. A new method of rat hepatic arterycatheterization via the left common carotid artery (LCCA) isdescribed. The LCCA is repaired after catheterization. Thecatheterization procedures included the following:(1) opening the rat�s abdominal cavity and exposing theportion of abdominal aorta at the level of the celiac trunk;(2) separating and exposing the LCCA; inserting a micro-guidewire and microcatheter set into the LCCA via anincision; after placement into the descending aorta, themicroguidewire and microcatheter are maneuvered into thehepatic artery under direct vision; (3) after transcathetertherapy, the catheter is withdrawn and the incision at theLCCA is repaired. This technique was employed on 60 maleSprague-Dawley rats with diethylnitrosamine-induced livercancer, using a 3F microguidewire and microcatheter set.Selective hepatic artery catheterization was successfullyperformed in 57 rats. One rat died during the operation andfive rats died within 7 days after the procedure. It isenvisaged that as experience increases, the catheterizationsuccess rate will increase and the death rate will decrease. Anew approach for selective hepatic artery catheterization viathe LCCA in rats is introduced, which makes repeat cath-eterization of this artery possible and allows large emboli-zation particles to be delivered by using a 3F catheter.

Key words: Rat—Carotid artery—Hepatic artery—Cathe-terization—Hepatocellular carcinoma

Selective catheterization of the rat hepatic artery is a tech-nique commonly used for the research of transcathetertherapy for liver cancer, including the study of pharmaco-kinetics and pharmacodynamics of transcatheter drugdelivery and transcatheter embolization [1–3].

Whereas selective catheterization of the hepatic arteryvia the femoral artery route is feasible in large animals suchas dogs and pigs, it is difficult to perform in rats. Until nowthe most commonly used techniques for rat hepatic arterycatheterization is the method described by Lindell et al. [1].With that method, the rat�s abdominal cavity is opened, anda small catheter is inserted into the gastroduodenal arteryand maneuvered upward into the hepatic artery. Afterwithdrawal of the catheter, the gastroduodenal artery is li-gated. One of the drawbacks of this procedure is ligation ofthe gastroduodenal artery, which might cause ischemia ofthe gastrointestinal tract. More importantly, this procedurecan be carried out only once. Repeat catheterization of thehepatic artery is not possible.

Here we describe a method of catheterization of the rat�shepatic artery via the left common carotid artery (LCCA).After removal of the catheter, the LCCA is repaired.

Materials and Methods

Catheterization Procedure

Step 1: The rat is anesthetized and its abdominal cavity opened.The left posterior peritoneal cavity is exposed by pushing theintestines to the right side. The fascia layer over the abdominalaorta is gently separated. The superior mesentery artery (SMA)is identified; the celiac trunk can be found 0.3–0.5 mm abovethe SMA. The portion of the aorta around the level of the celiactrunk is exposed (Fig. 1A). The opened abdominal cavity isthen covered with normal saline wetted gauze.

Step 2: A 4–5-cm-long skin incision at the midline of the left neckabove the lower edge of the thyroid cartilage is made. The

*Current address: AstraZeneca R&D, Alderley, Macclesfield SK10 4TG,UK.Correspondence to: Xiangping Zhou; email: xiangpingzhou46@163.com

ª Springer Science+Business Media, Inc. 2006Published Online: 2 May 2006CardioVascular

and InterventionalRadiology

Cardiovasc Intervent Radiol (2006) 29:1073–1076

DOI: 10.1007/s00270-005-8268-3

LCCA is exposed by blunt dissection between the sternohyoid,sternomastoid, and omohyoid muscles, and its sheath is opened.The left vagus nerve is gently separated from the LCCA. Asegment of approximately 2 cm of the LCCA is separated andexposed. The distal end of the dissociated LCCA is clampedwith a bulldog clamp, and another bulldog clamp and onerubber band is put around the proximal end of the dissociatedLCCA (Fig. 1B). When the bulldog clamp at the proximal endis released, the tightness of the rubber band around the arterycan be adjusted to control the blood flow during the operation.The dissociated LCCA is held up gently and an oblique incisionis made with a pair of ophthalmic scissors. The width of theincision should be no more than half of the vascular perimeter.The microguidewire and microcatheter set is inserted into theLCCA. After the catheter has been placed into the LCCA, thetip of the guidewire is turned to the left so that cannulation ofthe descending aorta is achieved (otherwise, the guidewiremight be misled to the ascending aorta). The gauze covering theabdominal cavity is removed and the celiac trunk is exposed.When the guidewire is sent down to the descending aorta to thelevel of the opening of the celiac trunk, the microguidewire isrotated to maneuver its tip into the celiac trunk under directvision. This maneuver can be sometimes helped by one fin-

gertip of the operator or a cotton-tipped applicator. The mi-crocatheter is followed through the microguidewire into thehepatic artery (Fig. 1C).

Step 3: After the angiography and transcatheter drug and/orembolization agent delivery, the catheter is withdrawn. Theincision in the LCCA is repaired using the conventional mi-crosuturing technique with three to five simple interrupted su-tures of size 8-0 Ethicon Prolene suture (Johnson & Johnson,USA) (Fig. 1D). To prevent thrombosis formation, saline con-taining 25 IU/ml heparin is applied on the operation fields atconsistent intervals. In total about 2–3 ml was used per rat. Atthe end of the operation, the heparinized saline at the operationfield is flushed away with standard normal saline. The incisionson the neck and abdomen are sutured layer-by-layer. Penicillinpowder can be sprayed on the wounds to prevent infection.

Experiment

The above-described technique was employed in the followingstudy. Sixty male Sprague-Dawley (SD) rats (346.85 € 82.27 g;age: 7 months) with diethylnitrosamine (DENA)-induced livercancer were used. The animals were from the Experimental AnimalCenter of Sichuan University, Chengdu, China. The hepatic artery

Fig. 1. Catheterization procedures. (A) Topography ofabdominal aorta with the celiac trunk and superior mesenteryartery in rats. AO: abdominal aorta; CT: celiac trunk; SMA:superior mesentery artery. (B) Dissociated left common car-otid artery with two bulldog clamps. LCA: left common carotidartery. (C) The microcatheter in the hepatic artery lumen seenthrough the vascular wall during the operation. Green arrows:

portal vein; yellow arrows: hepatic artery with microcatheter;white arrows: microcatheter within hepatic artery; blue arrow:the tip of microcatheter; black arrows: hepatic artery withoutmicrocatheter inside. (D) Left common carotid artery aftersuture of the arteriotomy (blue arrow). There is blood filling inboth sides of the incision site, indicating continuity of the arterylumen. There is no blood exudation.

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catheterization procedure was part of a larger study in which someantitumor agents were evaluated. Before the catheterization,magnetic resonance imaging was performed to confirm the tumorburden in the rat livers. The operations were carried out in theDigital Substraction Angiography (DSA) suite under standardsurgical aseptic conditions. Rats were anesthetized with intraperi-toneal injection of 1% pentobarbital sodium (30 mg/kg bodyweight). The microguidewire and microcatheter set were 3F Spe-cial Systems (SP) (Terumo Co., Fijinomiya, Japan). Angiographywas performed with the Siemens FA DSA system (power 100 kW,Axiom Artis FA; Siemens, Frankfurt, Germany) and a Mark VProvis injector system (Medrad, Indianola, PA). The contrast agentwas Omnipaque 300 (Ansheng Pharmaceutical Co., Shanghai,China). The image collecting speed was set at 7.5 frame/sec for 24sec until the end of the portal phase. The speed of the contrastagent flow was 0.3 ml/sec, the pressure was 100 psi, and the totalcontrast agent volume was 2.0 ml/kg. The rats were observed for 1week after this session of experimentation.

This study was approved by the Animal Research Committee ofour institution and was carried out according to the InstitutionalGuidelines for the Care and Use of Animals.

Results

Selective hepatic artery catheterization was successfullyperformed on 57 rats. Occasionally, the internal diameter ofthe LCCA of a low-weight rat (such as the rats less than300 g in our group of rats) can be smaller than the 3Fcatheter, but the artery wall usually has good elasticity, andsuccessful catheterization can still be feasible. In rats withsuccessful hepatic artery catheterization, high-quality angi-ograms were obtained in all of these animals (Fig. 2).

In the early phase of this study, two cases of failureduring the operation were caused by adhesion of the LCCAinner wall to the catheter at the incision site. Later, werealized that covering the dissociated portion of the LCCA

with wet saline gauze or tampon or moistening the dissectedportion of the LCCA and the nearby catheter with wet salinegauze or tampon every 1–2 min could avoid this problem.After this precaution, adhesion of arterial inner walls to thecatheter did not happen again. In another animal, the livertumor invaded the celiac trunk and made selective cathe-terization impossible. This animal died due to the attempt toseparate the celiac trunk from the tumor-encased abdominalaorta.

Five animals died within 7 days after the experimentalprocedure. Two animals died at day 1 and day 3 postoper-ation due to the damage to the abdominal lymphatics. Thedamage to the abdominal lymphatics can be seen by theexudation of ‘‘milk-colored’’ lymphatic fluid during theoperation. Thereafter, special attention was paid to the cis-terna chyli, the intestine lymphatic trunk, and the right andleft lumbar lymphatic trunks during the operational process,and no further deaths occurred because of this.

Two rats died from tumor hemorrhage as demonstratedpostmortem. One rat died 24 h postoperation, and it wasconsidered that the surgical procedures induced the tumorhemorrhage. Another rat died at day 5 postoperation; it isunknown whether the surgery was the cause. In both ofthose two animals, the liver tumor burden was extensive.Another rat died 48 h after the operation. The exact reasonwas unknown; compromised liver function, large tumorburden, and surgical trauma are the likely causes.

Discussion

We introduced a new approach for selective hepatic arterycatheterization in rats, which makes repeat catheterization of

Fig. 2. DSA of a rat liver with tumor. Multiple tumor stainsare shown. C: catheter; CT: celiac trunk; RHA: right hepaticartery; LHA: left hepatic artery; GDA: gastroduodenal artery;TS: one of the tumor stains.

Fig. 3. Ten days after the first catheterization and suture ofthe arteriotomy at the left common carotid artery in a healthyrat. The left common carotid artery is exposed. Althoughthere is mild adhesion around the carotid artery, it can beseparated for repeat catheterization and its lumen remainscontinuous. Blue arrow: the repaired incision at the artery.

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this artery possible. Introducing a catheter system into theaorta via a carotid artery in rats has been reported [4, 5]. Inmany cases, the carotid artery is ligated after the catheteri-zation [4, 5]. Because passage of a catheter along the rightcarotid artery might result in it passing down the ascendingaorta, the left carotid is employed. Compared with Lindellet al.�s approach in which ligation of the gastroduodenalartery is necessary after the operation [1], our approachmight have less negative impact on the blood supply to thedigestive system. An additional advantage of this approach isthat a larger catheter can be inserted into the hepatic arterythan the gastroduodenal artery approach, as the gastroduo-denal artery in rats is very small. This allows the adminis-tration of larger embolization particles. The LCCA routedescribed here can also be used for catheterization of arteriesof other visceral organs in rats. This technique can also beused in combination with the gastroduodenal artery route forrat hepatic artery catheterization for repeat procedures.

The technique of microvascular anastomosis has beenwell reported [6, 7]. Using a technique with a neodymium–YAG laser to anastomose arteries 0.8–1.0 mm in diameter,Jain [6] reported the patency rates to be as high as 92.5%. Inthe cases of LCCA incision repair failure, the ligation of thecommon carotid artery on one side would not be expected tohave dramatic effects on the rat, as a powerful collateralcirculation mechanism exists [8, 9]. One disadvantage ofour technique is that the abdominal cavity has to be openedto facilitate the guidewire to enter celiac trunk and hepaticartery. However, we found that it was very difficult tocatheterize the hepatic artery with the guidewire/catheter setinserted via the LCCA under X-ray guidance.

The rats in this study with liver tumor burden did notactually undergo repeat hepatic artery catheterization. Theprimary aim of the study was to evaluate some antitumoragents. Repeated hepatic artery catheterization and drugdelivery were not required according to the study design.However, additional pilot experiments were carried out in alimited number of healthy rats to assess the feasibility ofrepeat hepatic artery catheterization via the LCCA route,especially to investigate the lumen continuity of the LCCAafter the catheterization, and whether postoperation adhe-

sion around the involved arteries in the abdomen and theneck would cause difficulty for the second catheterization.Our pilot study�s results were satisfactory (Fig. 3), andfurther study is planned with a larger number of animals tovalidate these initial results.

Regarding the failure rate of our catheterization, twocases of catheter–carotid artery adhesion could have beenavoided. The mortality rate can be reduced by increasedexperience with cases with lymphatic injury. If the studywas done in healthy rats, the mortality rate could be furtherreduced.

In conclusion, a new approach for selective catheteriza-tion of the hepatic artery via LCCA is studied. This ap-proach can be used when repeat catheterization is requiredor when large embolization particles need to be adminis-tered via a catheter.

Acknowledgments. We are grateful to the China Medical Board of NewYork and the TCM Administration Bureau of Sichuan Province, China fortheir grant support of our research (CMB 82-412 and TCM 2004B03,rspectively).

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