Gary C. Lantz

Small intestinal submucosa as a large diameter vascular graft in the dog

Autogenous saphenous vein and synthetic materials, such as Dacron and expanded polytetrafluoroethylene, have been used extensively as vascular grafts with moderate success. Improved success rates for vascular graft surgery may be possible if superior graft material was available. We tested the use of autogenous small intestinal submucosa (SIS) as a large diameter (10 mm) vascular graft in the infrarenal aorta of 12 dogs. One dog died with graft thrombosis within 48 hr of surgery. Nine dogs were sacrificed at various times during a 52-week post-surgical period and showed patent grafts without infection, thrombosis, intimal hyperplasia, or adverse effects upon blood pressure. There was no ultrastructural evidence of endothelial cell growth on the luminal surface of the SIS graft which was composed of a dense, non-thrombogenic, organized collagenous connective tissue. The SIS material was approximately one order of magnitude less elastic than natural aorta and showed an immediate dilatation of approximately 18% after exposure to the systemic blood pressure. However, there was no progressive dilatation during the 52-week postsurgical period. Two dogs remain alive at 8 and 52 weeks post-surgery with patent grafts as determined by positive contrast radiography and Doppler studies. We conclude that autogenous small intestinal submucosa can be successfully used as a large diameter arterial graft in the dog and is worthy of further investigation.

Small Intestinal Submucosa as a Vascular Graft: A Review

Continuing investigations of vascular graft materials suggest that unacceptable graft complications continue and that the ideal graft material has not yet been found. We have developed and tested a biologic vascular graft material, small intestine submucosa (SIS), in normal dogs. This material, when used as an autograft, allograft, or xenograft has demonstrated biocompatibility and high patency rates in aorta, carotid and femoral arteries, and superior vena cava locations. The grafts are completely endothelialized at 28 days post-implantation. At 90 days, the grafts are histologically similar to normal arteries and veins and contain a smooth muscle media and a dense fibrous connective tissue adventitia. Follow-up periods of up to 5 years found no evidence of infection, intimal hyperplasia, or aneurysmal dilation. One infection-challenge study suggested that SIS may be infection resistant, possibly because of early capillary penetration of the SIS (2 to 4 days after implantation) and delivery of body defenses to the local site. We conclude that SIS is a suitable blood interface material and is worthy of continued investigation. It may serve as a structural framework for the application of tissue engineering technologies in the development of the elusive ideal vascular graft material.

Small Intestinal Submucosa as a Small-Diameter Arterial Graft in the Dog

Autogenous saphenous vein, human umbilical vein, modified bovine collagen, Dacron, and PTFE have been used as small-diameter arterial grafts with moderate success. We tested autogenous small intestine submucosa as a small-diameter arterial graft in both a carotid and femoral artery (mean ID 4.3 mm) of 18 dogs (total of 36 grafts). All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by Doppler ultrasound techniques and angiography. Two grafts ruptured and 5 grafts occluded by 21 days after surgery. One graft became occluded at 14 weeks. Fifteen dogs were sacrificed at periodic intervals until 48 weeks after surgery. Patent grafts had no evidence of infection, propagating thrombus, or intimal hyperplasia. Graft aneurysmal dilation occurred in 4 grafts (11%). The grafts were composed of a dense organized collagenous connective tissue with no evidence of endothelial cell growth on the smooth luminal surface. Three dogs are alive at 76 to 82 weeks after surgery. Overall, graft patency was 75%. Graft patency after cessation of anticoagulation therapy was 92.3% (12 of 13 grafts). We conclude that autogenous small intestinal submucosa can be used as a small-diameter arterial graft in the dog and is worthy of further investigation.

Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model

PURPOSE Prosthetic graft infection represents a most challenging complication to the vascular surgeon. Although expanded polytetrafluoroethylene (ePTFE) grafts have an acceptable patency rate, especially in the large-diameter arterial location, bacterial contamination of this material usually requires surgical removal of the graft. METHODS We compared the resistance of large-diameter ePTFE grafts and grafts constructed of small intestinal submucosa (SIS) to deliberate infection with Staphylococcus aureus. Eighteen dogs were divided into two equal groups, and the infrarenal aorta was replaced with either ePTFE or SIS graft material. One hundred million S. aureus organisms were deposited directly on the graft at the time of surgery, and the dogs were observed for 30 days. RESULTS One dog with an ePTFE graft died of hemorrhage from anastomosis site at 21 days. Of the remaining eight dogs with ePTFE grafts, four had positive culture results from the removed graft material, and all had histologic evidence for persistent infection. These dogs also had chronic fever, and the average white blood cell count at day 30 was 15,600/mm3. All nine dogs with SIS grafts had patent grafts, were afebrile after the first week, had an average white blood cell count of 11,500/mm3 at 30 days (p value = NS), had negative culture results, and had the histologic appearance of graft remodeling with collagen that was free of active inflammation. CONCLUSIONS We conclude that large-diameter arterial SIS grafts are more resistant to persistent infection with S. aureus than ePTFE grafts in this dog model of deliberate bacterial inoculation.

Small intestinal submucosa as a superior vena cava graft in the dog.

Autogenous spiral vein grafts and ePTFE have been used for reconstruction of the superior vena cava with moderate success. We tested autogenous small intestine submucosa as a superior vena cava interpositional graft in nine dogs. All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by serial venography. One dog died from excessive anticoagulation. Eight dogs were sacrificed at periodic intervals until 72 weeks after surgery. Patent grafts had no evidence of thrombosis, aneurysm, or stenosis. The grafts consisted of dense, organized collagenous connective tissue with a complete endothelial cell layer on the luminal surface. Two dogs are alive at 28 and 34 months after surgery. Graft patency was 89% (eight of nine grafts). We conclude that autogenous small intestine submucosa can be used as a superior vena cava graft in the dog and is worthy of further investigations.

A prospective study of survival and recurrence following the acute gastric dilatation-volvulus syndrome in 136 dogs.

Dogs (n = 136) with gastric dilatation-volvulus (GDV) syndrome were followed over time to measure recurrence and mortality rates and to identify prognostic factors. Thirty-three (24.3%) died or were euthanized during the first seven days. Of 85 cases that were followed for up to three years, nine (10.6%) cases each had a recurrence of GDV and seven (8.2%) cases died or were euthanized. The median survival times for cases that had gastropexies and those that did not were 547 and 188 days, respectively. Depressed or comatose cases on admission were three and 36 times, respectively, more likely to die than alert cases, while cases with gastric necrosis were 11 times more likely to die.

Morphologic study of three collagen materials for body wall repair

BACKGROUND The search for ideal prostheses for body wall repair continues. Synthetic materials such as polypropylene mesh (PPM) are associated with healing complications. A porcine-derived collagen-based material (CBM), small intestinal submucosa (SIS), has been studied for body wall repair. Renal capsule matrix (RCM) and urinary bladder submucosa (UBS) are CBMs not previously evaluated in this application. This is the first implant study using RCM. MATERIALS AND METHODS Full-thickness muscle/fascia ventral abdominal wall defects were repaired with SIS, RCM, UBS, and PPM in rats with omentum and omentectomy. A random complete block design was used to allot implant type to each of 96 rats. Healing was evaluated at 4 and 8 weeks. Adhesion tenacity and surface area were scored. Implant site dimensions were measured at implantation and necropsy. Inflammation, vascularization, and fibrosis were histopathologically scored. Data were compared by analysis of variance (P < 0.05). RESULTS PPM produced a granulomatous foreign body response in contrast to the organized healing of CBM implants. CBM mean scores were lower than PPM scores for adhesion tenacity, surface area, and inflammation at each follow-up time for rats with omentums (P < 0.02). The CBMs had less tenacity and inflammation than PPM at each follow-up time in omentectomy groups (P < 0.008). Wound contraction was greater for PPM (P < 0.0001) for all rats. CONCLUSIONS RCM and UBS were similar to SIS invoking reduced inflammation, adhesion, and contraction compared to PPM. The fibrotic response to PPM was unique and more intense compared to CBMs. These CBM implants appear morphologically acceptable and warrant continued investigation.

Diet-Related Risk Factors for Gastric Dilatation-Volvulus in Dogs of High-Risk Breeds

A nested case-control study was conducted among 1634 dogs with complete diet information in a 5-year prospective study to determine diet-related risk factors for gastric dilatation-volvulus (GDV). Cases included 106 dogs that developed GDV; controls included 212 dogs without GDV that were frequency matched to cases by year of GDV onset. Proportionate energy consumed from major food types and from carbohydrates was determined. Dogs were categorized as consuming either a low volume or high volume of food based on the median number of cups of food fed per kg of body weight per meal. Dogs fed a larger volume of food per meal were at a significantly (P<0.05) increased risk of GDV, regardless of the number of meals fed daily. For both large- and giant-breed dogs, the risk of GDV was highest for dogs fed a larger volume of food once daily.

SURFACE MODIFICATION WITH PEO-CONTAINING TRIBLOCK COPOLYMER FOR IMPROVED BIOCOMPATIBILITY : IN VITRO AND EX VIVO STUDIES

Poly(ethylene oxide) (PEO) has been frequently used to modify biomaterial surfaces for improved biocompatibility. We have used PEO-polybutadiene-PEO triblock copolymer to graft PEO to biomaterials by gamma-irradiation for a total radiation dose of 1 Mrad. The molecular weight of PEO in the block copolymer was 5000. In vitro study showed that fibrinogen adsorption to Silastic, polyethylene, and glass was reduced by 70 to approximately 95% by PEO grafting. On the other hand, the reduction of fibrinogen adsorption was only 30% on expanded polytetrafluoroethylene (e-PTFE). In vitro platelet adhesion study showed that almost no platelets could adhere to PEO-coated Silastic, polyethylene, and glass, while numerous platelet aggregates were found on the ePTFE. The platelet adhesion in vitro corresponded to the fibrinogen adsorption. When the PEO-grafted surfaces were tested ex vivo using a series shunt in a canine model, the effect of the grafted PEO was not noticeable. Platelet deposition on ePTFE was reduced by PEO grafting from 8170 +/- 1030 to 5100 +/- 460 platelets 10(-3) microm2, but numerous thrombi were still present on the PEO-grafted surface. The numbers of platelets cumulated on Silastic, polyethylene, and glass were 100 +/- 80, 169 +/- 35, and 24 +/- 22 platelets 10(-3) microm2, respectively. This is about 35% reduction in platelet deposition by PEO grafting. While the numbers of deposited platelets were small, the decreases were not as large as those expected from the in vitro study. This may be due to a number of reasons which have to be clarified in future studies, but it appears that in vitro platelet adhesion and fibrinogen adsorption studies may not be a valuable predictor for the in vivo or ex vivo behavior of the PEO-grafted surfaces.

A model of left ventricular dysfunction caused by intracoronary adriamycin

Experimental evaluation of new therapy for congestive heart failure has been hampered by the lack of a simple and reliable animal model of heart failure. This study was undertaken to develop a canine model of chronic left ventricular dysfunction. A left thoracotomy was performed in 9 adult mongrel dogs. A 1.5-mm Silastic (Dow Corning) catheter with an attached subcutaneous access port was positioned in the left main coronary artery. Six animals received five weekly infusions of Adriamycin (doxorubicin hydrochloride) (10 mg/wk), and 3 received saline solution. Hemodynamic studies were performed before insertion of the catheter and 2 weeks after completion of the infusions. In animals that received Adriamycin, rest ejection fraction declined from 0.54 +/- 0.03 to 0.35 +/- 0.03, cardiac output fell from 5.6 +/- 0.6 to 3.9 +/- 0.5 L/min, and left ventricular end-diastolic volume increased from 76 +/- 9 to 99 +/- 12 mL (p less than 0.05). There was a small increase in right atrial pressure (2.7 +/- 1 versus 5.7 +/- 1 mm Hg) but no change in right ventricular ejection fraction (0.31 +/- 0.04 versus 0.30 +/- 0.03). In no animal did alopecia, weight loss, neutropenia, or anemia develop. Histological changes consistent with Adriamycin-induced cardiac toxicity were found in each dog. No significant hemodynamic or histological changes occurred in the control animals. Administration of Adriamycin into the left main coronary artery causes left ventricular dysfunction without resulting in systemic side effects or compromising right ventricular function. This animal model could be used to evaluate the effects of new possible therapy, such as cardiomyoplasty, on left ventricular failure.