TECHNICAL NOTE

Testing Percutaneous Arterial Closure Devices: An Animal Model

Rui-Fang Ni Æ Pawanrat Kranokpiraksa ÆDusan Pavcnik Æ Hideaki Kakizawa Æ Barry T. Uchida ÆFrederick S. Keller Æ Josef Rosch

Received: 20 May 2008 / Accepted: 8 August 2008 / Published online: 9 September 2008

� Springer Science+Business Media, LLC 2008

Abstract The ovine superficial femoral artery was used

for testing the efficacy of percutaneous arterial closure

devices (PACDs) in their developmental stage. Two topical

devices containing chitostan, one staple-mediated PACD

and a porcine small intestinal submucosa plug, were tested

by follow-up angiography in 37 sheep. Absence or pres-

ence of bleeding and time to bleeding cessation were the

main criteria for evaluation of PAVD efficacy. The results

of these tests directed modification of individual PACDs

and improved their efficacy.

Keywords Animal model � Experimental device �Hemostasis � Percutaneous arterial procedures

Introduction

Numerous percutaneous arterial closure devices (PACDs)

are now available. Madigan et al., in 2007, reviewed 14

PACDs used for achieving hemostasis in the femoral artery

after diagnostic or therapeutic procedures [1]. Other new

PACDs are being developed and/or tested [2]. Medline

cites 1398 papers on the subject of PACDs, indicating their

popularity. The vast majority of these papers are clinical in

nature and discuss the advantages and occasional compli-

cations of PACDs in patients. However, we have found

only three papers testing PACDs experimentally in ani-

mals. One of these compared two suture-mediated PACD

in swine [3], the other evaluated application of chitosan in

dogs [4], and the third used dogs to test balloon catheters

with the addition of a precoagulant consisting of microfi-

brillar collagen and thrombin [5].

We have been asked by three companies to test their

PACDs in their developmental stages. These PACDs

include one topical or pad device, the Clo-Sur-Pad (Scion

CardioVascular, Miami, FL), and one sealing device, the

Stat-Seal (Innovasa Corp., Eugene, OR). Both are chemi-

cally impregnated with a procoagulant material—

chitosan—and are applied with manual compression to the

puncture site or into the puncture tract. The third PACD

tested was the Cardica Closure Device (Cardica Inc.,

Redwood City, CA), a staple-mediated device. A home-

made small intestinal submucosa (SIS) plug inserted into

the puncture tract, similar to the plug used for aneurysmal

sac embolization, was the fourth type of PACD we tested

[6]. We selected an ovine model for these tests because the

size of sheep femoral arteries is close to that of humans [7].

Testing the PACDs was done using angiography. Absence

of contrast extravasation on follow-up angiograms and

length of time for cessation of bleeding were the main

criteria for evaluating the efficacy of the PACD. Angiog-

raphy was the primary assessment of device efficacy

because observation of unsatisfactory results in these

developmental devices prompted modifications that may

lead to device improvements. The intention of this report is

to describe our use of this model to evaluate PACDs.

Materials and Methods

The studies were approved by the Institutional Animal

Care and Use Committee of the Oregon Health & Science

University. Altogether, 37 adult female sheep weighing 57

R.-F. Ni � P. Kranokpiraksa � D. Pavcnik (&) � H. Kakizawa �B. T. Uchida � F. S. Keller � J. Rosch

Dotter Interventional Institute, Oregon Health Sciences

University, L342, 3181 SW Sam Jackson Park Road, Portland,

OR 97201, USA

e-mail: pavcnikd@ohsu.edu

123

Cardiovasc Intervent Radiol (2009) 32:313–316

DOI 10.1007/s00270-008-9426-1

to 72 kg were used. All sheep were euthanized after PACD

evaluation. In 16 sheep, PACD testing was the only study.

In 21 sheep, PACD testing was performed following

evaluation of venous valves.

Testing Techniques

The procedures were done in an angiography room

equipped with a cardiac mobile system (GE/OEC 9800; GE

Medical Systems, OEC, Salt Lake City, UT). Digital

imaging was used for fluoroscopy and angiography. Sub-

traction angiography was performed with an injector

(Medrad Mark Plus; MEDRAD, Inc., Warrendale, PA).

Animals were tranquilized with intravenous ketamine

HCl, 2.0 mg/lb (100 mg/mL; Fort Dodge Animal Health,

Fort Dodge, IA), and midazolam HCl, 0.05 mg/lb (5 mg/

mL; Bedford Laboratories, Bedford, OH). Atropine sulfate

(4 mg; American Regent Laboratories, Shirley, NY) was

also administered intravenously to control salivation. The

animals were then intubated endotracheally. General

anesthesia was maintained with 2–2.5% isoflurane (Abbot

Laboratories, North Chicago, IL) at 2 L/min oxygen. The

sheep were placed on their back with their hind limbs in

moderate abduction. The anterior neck area was shaved and

the right common carotid artery (CCA) was exposed via a

median cervical incision. A short segment (*5 cm) of the

CCA was dissected free, and both proximal and distal ends

of the exposed CCA were fixed with umbilical tape. A

5-Fr, 7-cm-long micropuncture kit (Cook Medical,

Bloomington, IN) was introduced in a retrograde direction

into the CCA. After exchange for a 0.035-in. guidewire, a

Simmons catheter (Cook Medical) was introduced and

advanced into the descending aorta. The oblique position of

the C-arm system facilitated catheter advancement into the

descending aorta. Intra-arterial heparin (5000 U/0.1 ml)

was then administered directly via the 6-Fr sheath and

additional heparin was administered later as needed to keep

ACT values at a level two times higher than the initial

baseline.

For iliac angiography, the Simmons catheter was

exchanged for a multiside hole catheter. Angiography was

done in a slightly oblique projection, with the injection of

12 ml Hypaque 76 (Amersham Health Inc., Princeton, NJ)

in 2 s. The diameter of the superficial femoral artery (SFA)

was measured with reference to a dime’s diameter (Fig. 1).

We used SFA, because the ovine common femoral artery

(CFA) differs anatomically from that of humans. The CFA

puncture is too deep, and reliable manual compression

would be difficult to achieve [7]. A micropuncture set

(Cook Medical) was used for a single-wall retrograde

arterial access using roadmap guidance. The skin was

entered just below the inguinal crease and the SFA was

catheterized. Depending on the company protocol, a 6- or

8-Fr, 25-cm-long sheath was inserted and kept in the artery

for 10 min. After its removal, the tested topical PACD was

applied to cover the puncture site or a Siling device and SIS

plug were inserted into the puncture tract and compressed

by hand for 5 min. In the case of the Cardica closure

device, manual compression lasting more than 2 min was

applied after stapling. Immediately after release of manual

compression, follow-up angiography was performed to

search for evidence of bleeding. If extravasation was seen,

manual pressure was continued for 2 or 5 more min, fol-

lowed by repeat angiography. This process was continued

until no extravasation was seen.

The catheter was then moved into the opposite external

iliac artery and arteriography was performed. After SFA

diameter was measured, the artery was accessed and the

sheath was introduced. After withdrawal of the sheath, the

PACD was tested on the opposite side in a similar fashion.

To obtain more data on the PACDs we were testing, we

Fig. 1 Selective arteriogram prior to puncture of the superficial

femoral artery (SFA). CFA, common femoral artery; DFA, deep

femoral artery; MB, muscular branches; D, dime

314 R.-F. Ni et al.: Testing Percutaneous Arterial Closure Devices

123

often went back to a previously accessed artery, alternating

the sites. We performed a second puncture above the pre-

vious entrance into the SFA.

At the end of testings, puncture sites were evaluated and

graded for the presence of hematomas, which were graded

as small or large. A groin area fullness with a prominence

\1 cm was considered a small hematoma. The animal was

then euthanized and the femoral arteries were dissected and

evaluated for the presence or absence of wall damage.

Results

Diameter of the SFAs above the origin of muscular bran-

ches varied from 5.4 to 6.5 mm, with a mean of 5.98 mm.

The diameter of the SFA decreased *1 mm below the

origin of the muscular branches. The abdominal wall

overlying the area of skin puncture often had to be retracted

superiorly to access the groin area. The SFA access sites

were located in a SFA segment *3 cm long, proximal to

Fig. 2 Testing of a topical

percutaneous arterial closure

device (PACD). (A)

Arteriogram prior to puncture of

the superficial femoral artery

with an 8-Fr sheath. (B)

Arteriogram after application of

a topical PACD and 5 min of

compression shows significant

extravasation at the puncture

site. (C) Arteriogram after a

further 5 min of manual

compression does not show any

extravasation

Fig. 3 Testing of a staple-

mediated percutaneous arterial

closure device (PACD). (A)

Arteriogram after stapling of the

puncture site and 2 min of

manual compression

demonstrates significant

extravasation. (B) Arteriogram

after 2 more min of manual

compression shows only minor

extravasation. (C) Arteriogram

after 2 more min of manual

compression does not show any

extravasation. The PACD clip is

seen (arrowhead)

R.-F. Ni et al.: Testing Percutaneous Arterial Closure Devices 315

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the origin of its muscular branches. One-wall punctures

were easy to perform using roadmap guidance even in the

event of diffuse SFA spasm, which was often seen after the

first puncture.

Topical and sealing PACDs and SIS plugs were easy to

apply. On the other hand, there was a learning curve with

the staple-mediated device. We had to first learn how to

apply it properly with our angled puncture. After the device

was modified and we gained more experience, we were

able to deploy it smoothly. After removal of all 6-Fr

sheaths, all PACDs were effective. No bleeding was seen

on angiograms after 2 min of manual compression with the

staple-mediated device or after 5 min of compression with

the topical devices and SIS plugs. With use of the 8-Fr

sheath, the devices were less effective and bleeding was

seen on arteriography after 2 or 5 min of manual com-

pression in more than half of the cases. Extravasation

ranged from minimal to significant (Figs. 2, 3). Further

compression, however, was effective in most cases and

continued compression was needed in only three instances

(Fig. 3).

On gross examination, we saw large hematomas with the

first few staple-mediated devices when the staples were not

applied properly to the arterial puncture site. Otherwise,

only a small skin prominence was seen in some animals

with use of the 8-Fr sheath. Except for a small intimal

dissection in early stages of the staple-mediated device, we

did not see any wall damage of the punctured arteries.

Discussion

The sheep is a suitable animal model for testing of PACDs.

The ovine SFA (6 mm) is close to the human SFA (6–

7 mm) and the human CFA 6 to 7 mm) in size. This model,

however, has limitations. The results in the ovine model

cannot be directly applied to sick human femoral arteries

changed due to atherosclerosis. The depth of arterial

puncture in sheep is similar to that in an average-size

patient. The results in sheep, particularly with the use of

topical PACDs, cannot be directly applied to obese

patients, where the arterial puncture is quite deep. Also, the

type of artery punctured in sheep is different from that in

humans. The ovine anatomy allows easy puncture and

reliable compression of the puncture site of the SFA. The

SFA in sheep, however, is a more muscular artery and is

quite susceptible to spasm. The CFA that is the puncture

target in humans is an elastic artery and much less prone to

spasm. In sheep, however, puncture of the CFA is difficult

to perform because of the overlapping abdominal wall.

Abdominal wall overlap of the CFA would also prevent

testing PACDs that need manual compression after their

application. The CFA puncture is too deep, and reliable

manual compression would be difficult to achieve.

Even with these limitations, the ovine model with use of

angiography allowed us to obtain valuable information on

three types of PACDs: topical devices, a staple-mediated

device, and an SIS plug. These tests yielded useful

information for PACD manufacturers. Demonstration of

unsatisfactory results in these developmental devices

prompted modifications that led to device improvements.

Today, two of the four tested PACDs are in clinical eval-

uation or approved for clinical use. The ovine model also

allows comparison of the effectiveness of a new PACD

with that of standard manual compression or an established

device. Use of one SFA for the new device being tested and

the opposite SFA as a control site would give reliable

evaluation on the new PACD.

References

1. Madigan JB, Ratnam LA, Belli AM (2007) Arterial closure

devices. A review. J Cardiovasc Surg 48:607–624

2. Wang DS, Chu LF, Olson SE et al (2008) Comparative evaluation

of noninvasive compression adjuncts for hemostasis in percutane-

ous arterial, venous and arteriovenous dialysis access procedures. J

Vasc Interv Radiol 19:72–79

3. Hofmann LV, Sood S, Liddell RP et al (2003) Arteriographic and

pathologic evaluation of two suture-mediated arterial closure

devices in a porcine model. J Vasc Interv Radiol 14:755–761

4. Hoekstra A, Struszczyk H, Kivekas O (1998) Percutaneous

microcrystalline chitosan application for sealing arterial puncture

sites. Biomaterials 19:1467–1471

5. Gershony G, Brock JM, Powell JS (1998) Novel vascular sealing

device for closure of percutaneous vascular access sites. Cathet

Cardiovasc Diagn 45:82–88

6. Shoder M, Pavcnik D, Uchida B et al (2004) Small intestinal

submucosa aneurysm sac embolization for endoleak prevention

after abdominal aortic aneurysm endografting: a pilot study in

sheep. J Vasc Interv Radiol 15:69–83

7. Nakata M, Pavcnik D, Uchida B et al (2003) comparison of small

intestinal submucosa-covered and noncovered nitinol stents with

PTFE endographs in injured ovine femoral arteries: a pilot study.

CardioVasc Interv Radiol 26:459–467

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