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Biomedical subjects

Dusan Pavcnik

Publications and source records attributed to Dusan Pavcnik.

At least 19 recordsLinked to original sources

Comparison of the endothelialization of small intestinal submucosa, dacron, and expanded polytetrafluoroethylene suspended in the thoracoabdominal aorta in sheep.

PURPOSE: This study was undertaken to evaluate and compare endothelialization of small intestinal submucosa (SIS), Dacron, and expanded polytetrafluoroethylene (ePTFE) in high-pressure flow without aortic wall contact and to evaluate the suitability of SIS as a vascular graft material. MATERIALS AND METHODS: In 12 adult sheep, three types of membrane leaflets of similar thickness (approximately 200 mum) were suspended within large square stents without contact with the thoracoabdominal aortic wall: SIS (n = 12), Dacron (n = 12), and ePTFE (n = 12). Each animal received one leaflet of each material. Aortograms were obtained before and after percutaneous implantation and when the animal was killed at 8 weeks (n = 6) or 18 weeks (n = 6). Cell coverage and remodeling of SIS, Dacron, and ePTFE membranes were assessed by gross and histologic microscopic examinations. RESULTS: Thirty-five successfully implanted leaflets were evaluated. SIS showed progressive remodeling. Thirty-three leaflets exhibited thickening as a result of neointimal formation and endothelialization, most likely from circulating endothelial cells. Dacron exhibited the greatest and most progressing degree of neointimal formation and endothelialization, followed by SIS and then ePTFE. With SIS and ePTFE, neointimal formation decreased with time, but endothelialization was stable. Uneven neointimal formation and endothelialization on the outer surfaces and distal leaflet positions were seen. CONCLUSIONS: SIS showed progressive remodeling with moderate and regressive neointimal formation and moderate stable endothelialization. Further study of its durability and incorporation into the aortic wall needs to be performed to evaluate its suitability as a cover for aortic endografts.

Animals↗

Persistent left superior vena cava in sheep.

Persistent left superior vena cava (PLSVC) is a rare finding. To the best of our knowledge, this is the first report of PLSVC in sheep. In this case, PLSVC was confirmed using angiography.

Animals↗

Transcatheter placement of a low-profile biodegradable pulmonary valve made of small intestinal submucosa: a long-term study in a swine model.

OBJECTIVE: We sought to investigate a placement of a percutaneous low-profile prosthetic valve constructed of small intestinal submucosa in the pulmonary position in a swine model. METHODS: Twelve female farm pigs were stented at the native pulmonary valve to induce pulmonary insufficiency. Once right ventricular dilation occurred, the small intestinal submucosa valve was implanted. The pigs were followed up with transthoracic echocardiographic Doppler scanning. One animal died of heart failure before valve replacement. Animals were euthanized at 1 day, 1 month, 3 months, 6 months, and 12 months after valve implantation. RESULTS: The small intestinal submucosa pulmonary valve showed effective reversal of pulmonary regurgitation. There were no misplacements during deployment. There were no embolizations. One-year echocardiographic follow-up showed minimal regurgitation and no stenosis for a valve/vessel ratio of 0.78 or greater. Histologic examination demonstrated intensive remodeling of the small intestinal submucosal valve. Within 1 month, the surface was covered by endothelium, and fibroblasts invaded the interior. Over the following months, the small intestinal submucosal valve remodeled without apparent graft rejection. CONCLUSION: The small intestinal submucosa valve has the potential for graft longevity without the need for anticoagulation or immunosuppression. Histologic remodeling of the valve tissue provides a replacement capable of resembling a native valve that can be placed percutaneously with low-profile delivery systems.

Absorbable Implants↗

Significance of spatial orientation of percutaneously placed bioprosthetic venous valves in an ovine model.

PURPOSE: To investigate two spatial orientations of a percutaneously placed bicuspid second-generation bioprosthetic venous valve (SG-BVV) in the jugular vein (JV). MATERIALS AND METHODS: Twelve SG-BVVs, consisting of small intestinal submucosa attached to a nitinol frame were placed across a natural valve (NV) in the distal JV in six sheep. Six SG-BVVs were oriented as NV leaflets (group A) and the other six SG-BVVs were rotated 90 degrees to NV leaflets (group B). SG-BVV function was studied by venography performed immediately after placement and at 5 weeks after placement. Animals were killed at 5 weeks, and gross examinations were performed. RESULTS: Desired valve orientation after deployment was seen in all SG-BVVs. In group A, all valves exhibited good valve function on immediate and 5-week venography. At gross examination, leaflets were attached mostly at the valve base and free cusp areas were similar in both cusps with a mean of 154.8 mm2 +/- 45.6 for one cusp and 142 mm2 +/- 53.4 for the other cusp (P = .188). In group B, all valves showed good function on immediate venography and in five valves prior to killing. Valve attachment to the vein wall in this group involved a longer segment of leaflets and their free areas were smaller with a wide variety of cusp sizes. Mean free leaflet areas of opposing cusps measured 106.3 mm2 +/- 36.5 and 66.1 mm2 +/- 34.6, respectively (P = .025). Difference in leaflet areas between group A and group B was significant (P = .019). CONCLUSION: Proper spatial orientation of the SG-BVV at deployment is important for valve function and should have the same orientation as the NV.

Animals↗

Long-term optional retrievability of a new inferior vena cava filter in an ovine model.

Long-term retrievability of a new optional retrieval inferior vena cava (IVC) filter composed of a modified square stent and a modified Günther Tulip filter was tested in eight sheep. Eleven filters were placed into the IVC and eight were successfully retrieved 3-5 months after implantation. Incorporation of the filter struts into the IVC wall prevented its retrieval in three sheep at 3, 4, and 5 months after placement.

Animals↗

Prevention of coronary hyperreactivity in preatherogenic menopausal rhesus monkeys by transdermal progesterone.

OBJECTIVE: To test if transdermal progesterone (P) confers coronary vascular protection in surgically menopausal preatherosclerotic rhesus monkeys. METHODS AND RESULTS: Ovariectomized rhesus monkeys fed an atherogenic diet (AD) for 19 months were treated with an investigational transdermal P cream (n=7) or identical placebo cream (n=5) for 4 weeks. Aorta and carotids showed fatty streaks and Oil Red O staining demonstrated lipid deposition. Serum P levels in P-treated rhesus monkeys (0.6 ng/mL) were significantly greater than placebo (0.2 ng/mL). Significant elevation of cholesterol, LDL cholesterol, and HDL cholesterol, was noted in all animals. Lp(a) was significantly attenuated in the AD-fed P-treated monkeys. Coronary angiographic experiments stimulating vasoconstriction by intracoronary injections of serotonin plus U46619 showed exaggerated prolonged actions amplified by AD, but significant protection against severe prolonged vasoconstriction in P-treated monkeys. Immunocytochemistry confirmed co-expression of P and thromboxane prostanoid (TP) receptors in coronaries and aorta. Western blotting demonstrated TP receptor attenuation in vascular muscle after P treatment. CONCLUSIONS: Coronary hyperreactivity, a putative component of coronary artery disease mediated via increased vascular muscle thromboxane prostanoid receptors, can be prevented by subphysiological levels of P, not only in nonatherosclerotic (previously shown) but also in preatherosclerotic primates.

Administration, Cutaneous↗

Second-generation percutaneous bioprosthetic valve: a short-term study in sheep.

OBJECTIVES: To eliminate occasional tilting of the original bioprosthetic venous valve (BVV) a second-generation BVV has been developed. This study was performed to evaluate deployment, stability, and short-term function of the second-generation BVV in an animal model. METHODS: A second-generation percutaneously placed BVV consisting of a square stent and lyophilized small intestinal submucosa attached to a second square stent (DS BVV) or Z-stent (ZS BVV) were tested. DS BVVs (n = 32) were constructed with a nitinol (n = 28) or stainless steel double stent (n = 4), and ZS BVVs (n = 16) were made of nitinol (n = 8) or stainless steel (n = 4). BVVs were implanted percutaneously through a femoral vein approach into the jugular vein in 24 female sheep with an over-the-wire 13F or 10F delivery system. All BVVs were placed across the natural valve of the proximal jugular vein. Deployment, stability, and function of BVVs were studied at immediate venography with contrast medium injections peripheral and central to the BVVs. Animals underwent follow-up venography and were sacrificed at 6 weeks (n = 24). Gross pathologic examination was performed. RESULTS: Jugular vein diameter ranged from 9.8 to 14.4 mm (mean, 12.1 +/- 1.2 mm) in 24 sheep. The 10-mm to 12-mm valve was deployed in 27 jugular veins, and the 12-mm to 14-mm valve was deployed in 21 jugular veins. No tilting was seen at placement of 48 BVVs into the jugular veins, and all valves exhibited good function on immediate venograms. Angiographic competency for the nitinol and stainless steel ZS BVV (100%) was similar to that for the nitinol DS BVV (92.3%; P = .488) but was significantly better than for the stainless steel DS BVV at 6 weeks (50%; P = .03). Dysfunction of 4 valves was caused by either nitinol DS BVV oversizing (n = 2) or intimal hyperplasia with the stainless steel DS BVV (n = 2). CONCLUSION: Placement without tilting appears essential for proper valve function. The second-generation BVV enables placement without tilting. Exact matching of valve size with vein diameter is necessary for good valve function. CLINICAL RELEVANCE: At present there are no widely accepted surgical or percutaneous treatment options for deep chronic venous insufficiency. A manufactured, percutaneously implantable, nonimmunogenic and nonthrombogenic bioprosthetic venous valve that remains patent and competent over time is an attractive alternative to direct venous valve reconstruction or transplantation. our results and the potential for effective treatment with bioprosthetic venous valves warrants clinical research in carefully selected patients and may lead to an effective, minimally invasive treatment for deep chronic venous invasive treatment for deep chronic venous insufficiency.

Animals↗

Small intestinal submucosa aneurysm sac embolization for endoleak prevention after abdominal aortic aneurysm endografting: a pilot study in sheep.

PURPOSE: To percutaneously create an improved abdominal aortic aneurysm model of endoleak after endograft placement and to explore efficacy of small intestinal submucosal embolization of the residual aneurysmal sac for prevention of endoleaks. MATERIALS AND METHODS: Abdominal aortic aneurysm was created transluminally by over-dilation of a Palmaz stent in 12 sheep. Approximately 20% undersized endografts suspended between two stent-graft adapters were used to bridge the aneurysm in a manner that two lumbar pairs remained patent within the residual aneurysm sac. Size of the residual aneurysm sac was increased by placement of an undersized stent-graft consisting of damaged lyophilized small intestinal submucosal sheets sandwiched between two Zilver stents. In six sheep, residual aneurysm sacs were embolized by combining small intestinal submucosal sponge and small intestinal submucosal sheet pieces. The other six sheep served as the control group. Angiography performed immediately after the procedure was compared with follow-up angiography before the animals were killed at 1, 3, and 7 months. Gross and histologic examinations were also obtained. RESULTS: Aortic ruptures (n = 3) and dissections (n = 2) during aneurysm creation responded well to endograft placement. Eleven endografts were placed successfully, one was misplaced. The mean diameter of aneurysmal sac was 16 mm in the study and 15.2 mm in the control group. In the study group, in four sheep, the sac and seven pairs of lumbar arteries were occluded by embolization and remained obstructed by organized thrombus during the entire study. There were no type II endoleaks. Four type III new endoleaks developed without antegrade filling of lumbar arteries. In the control group, five animals had type I and II endoleaks at the initial studies. Only one sheep exhibited completely organized thrombosis of the aneurysmal sac and without endoleaks. In the other four sheep with partially organized sac thrombosis, endoleaks were unchanged. One type III endoleak occurred in this group. CONCLUSION: The combination of small intestinal submucosal sponge and small intestinal submucosal sheet pieces is a promising embolic material for occlusion of the residual sac after endovascular abdominal aortic aneurysm repair and for prevention of type II endoleaks.

Animals↗

Percutaneous transgastric technique for creating gastroenteric anastomoses in swine.

PURPOSE: To develop a percutaneous transgastric procedure for creating a stent-containing gastroenteric anastomosis (GEA). MATERIALS AND METHODS: Acute experiments were performed on eight pigs. A 10-F gastroduodenostomy sheath was used to insert guide wires and targeting devices in the retrogastric jejunal loop; a 6.5-F sheathed trocar needle was then introduced through a second gastric sheath to puncture and catheterize the jejunum through the back of the stomach. Two special sliding anchor pairs were introduced through the catheter to "sandwich" the gastric sheath to the jejunal wall. The jejunum was catheterized a third time between the anchor sets to create a GEA tract for insertion of a stent. The animals were killed at various periods as long as 1 month after the experiments. RESULTS: Snares were the most useful targeting devices for jejunal puncture. Single (n = 1) and double (n = 7) anchor-pair staples effectively prevented intraperitoneal leakage during and after insertion of 12-mm or 14-mm stents. Necropsy of six healthy animals at 5 days, 7 days, 14 days, and 4 weeks (n = 3) showed well-developed patent GEA anastomoses. There was one anesthetic death; one animal was killed at 4 days for obstructive ileus after a difficult transgastric jejunal catheterization. CONCLUSIONS: A GEA can be fashioned through a percutaneous gastrostomy with stapling anchors. This technique may have clinical applications for managing gastric outlet obstruction.

Anastomosis, Surgical↗

Fallopian tube occlusion with use of a small intestine submucosa device: evaluation in a rabbit model.

PURPOSE: The present study evaluates the short- and midterm efficacy of a small intestinal submucosa (SIS) device for fallopian tube occlusion in rabbits. MATERIALS AND METHODS: In a pilot study, several SIS device designs were tested for positional stability (absence of migration). The design selected for further testing consisted of a center of spongy SIS surrounded by an SIS sheet and held together by a 0.006-inch wire helix with two barbs. It was delivered on the tip of a short coaxial 3-F/5-F catheter set. Using this design, bilateral transuterine fallopian tube occlusion was performed in eight New Zealand White rabbits. Follow-up consisted of plain radiography at 2 weeks and hysterosalpingography at 6 weeks (n = 4 animals; eight tubes), 12 weeks (n = 2 animals; four tubes), or 24 weeks (n = 2 animals; four tubes). Thereafter, the animals were killed and the fallopian tubes were harvested for histologic evaluation. RESULTS: A single device was placed successfully in each fallopian tube. Fifteen of 16 devices (94%) remained in place throughout follow-up. One device migrated into the vagina at 2-week follow-up. Hysterosalpingography of the 15 tubes with occluders in place showed occlusion in seven of seven (100%) at 6 weeks, three of four (75%) at 12 weeks, and two of four (50%) at 24 weeks. Histologic evaluation revealed luminal occlusion by reorganized SIS containing macrophages, fibrocytes, and scant foreign-body giant cells. Only a mild inflammatory reaction was observed around the tube. In the animals with recanalization at 12 and 24 weeks, new channels were found alongside the original still-occluded fallopian tube lumen. CONCLUSIONS: The original lumen of the fallopian tube was effectively occluded by the SIS occluder, which was remodeled within the fallopian tubes of rabbits. Partial peripheral recanalization was observed over time.

Animals↗

Percutaneous prosthetic venous valves: current state and possible applications.

The small-intestinal submucosa square-stent bicuspid venous valve has shown the most promising results of all of the artificial venous valves developed. In long-term experimental studies in sheep, 25 valves were placed into the jugular veins and 88% exhibited good function, whereas 12% had decreased function because of valve tilting. Only 4% had partial thrombosis in the tilted valve. Valves also were placed in 3 patients. The bicuspid venous valves remained patent without thrombosis or other complications. Proper sizing and proper placement of the valves was critical to their function. The valve construction needs to be improved to prevent occasional tilting during their deployment.

Adult↗

Remodeling of suspended small intestinal submucosa venous valve: an experimental study in sheep to assess the host cells' origin.

PURPOSE: To investigate the origin of host cells during remodeling of small intestinal submucosa (SIS) square stent-based bicuspid venous valves (VVs). MATERIALS AND METHODS: Suspended VVs (SVVs) were developed by suspending VVs within bare square stents so the valve elements would not contact the vein wall after deployment. Eight SVVs were placed within the intrahepatic and infrahepatic inferior venae cavae (IVCs) of four adult female sheep. Eight standard VVs were implanted in the external jugular veins of these animals for comparison. At 5 weeks after placement, the devices were examined for stability and patency and the animals were killed. Gross, histologic, and scanning electron microscopic (SEM) examinations were performed. RESULTS: Follow-up spot radiographs and venography showed no migration of the devices, venous occlusion, or thrombus formation. All SVVs were intact without contact with the IVC wall. Six VVs were competent and two were slightly tilted with some reflux. Histologic study showed remodeling of SVVs and VVs with newly formed collagen fibers; fibroblasts and inflammatory cells were found penetrating the SIS leaflets and endothelial cells on the surface. SIS neovascularization was also present. There was no difference regarding SIS remodeling between SVVs and the free part of VV leaflets. The VV leaflets' bases were thicker compared to their free parts (P <.01). SEM examination showed endothelial cells on both sides of the SVVs and VVs. Endothelialization of the SVV central leaflet surfaces and both surfaces of the VV leaflets was more complete than that of the peripheral surfaces of the SVV leaflets. CONCLUSION: SIS-based valve remodeling occurs independently of vessel wall contact by recruitment of cells directly from the circulation.

Animals↗

A canine model for studying endoleak after endovascular aneurysm repair.

PURPOSE: The aim of this study was to create an animal model of endoleak after stent-graft placement for abdominal aortic aneurysm (AAA) in which a large aneurysmal sac would be preserved for the testing of techniques for its percutaneous occlusion. MATERIALS AND METHODS: Infrarenal AAAs were created in nine dogs by anastomosis of an isolated segment of the inferior vena cava to the right side of the abdominal aorta in combination with a large anterior patch from the external jugular vein. One hour later, animals underwent percutaneous implantation of polytetrafluoroethylene-covered Z stent endografts with three 3-mm-diameter holes through the fabric. Aortograms were obtained before and after surgery, after endograft placement, and at the time of animal sacrifice at 1 week or 1, 2, 3, or 6 months. Pressures within the aorta and the aneurysm sac were recorded before animal sacrifice. Gross and histologic evaluations of the specimens were then carried out. RESULTS: Immediately after endograft placement, all nine animals had artificial type III endoleaks with angiographic filling of lumbar arteries and veins. One animal died of surgical complications within 2 days of surgery and is not included in our data analysis. One aneurysm ruptured at 1 week. At completion of the study, six endografts were patent and two were occluded. The aneurysm sac had enlarged by approximately 50% in seven animals. At follow-up, type I endoleak was present in three animals, type II endoleak was present in three, and the artificial type III endoleak was present in all six animals with patent endografts. The pressure differential between aorta and aneurysm sac was 36 mm Hg, with a mean aortic pressure of 87 mm Hg +/- 13.3 and a mean aneurysmal sac pressure of 51 mm Hg +/- 28.1. The aneurysmal sac exhibited early thrombus formation at 1 week, which progressed to complete thrombosis in 1-6 months. CONCLUSIONS: The model is technically feasible but would be useful in testing occlusive techniques for residual aneurysm sacs only in the acute phase after endograft placement. It would be not reliable for chronic evaluation because of rapidly progressive thrombosis in most aneurysm sacs and occasional complete thrombosis of the AAA and endograft.

Animals↗

Comparison of small intestinal submucosa-covered and noncovered nitinol stents in sheep iliac arteries: a pilot study.

PURPOSE: To compare the biocompatibility and performance of nitinol endografts covered externally or internally with small intestinal submucosa (SIS) with bare nitinol stents in medium-sized arteries. MATERIALS AND METHODS: Eighteen nitinol Zilver stents were used: six externally SIS-covered endografts (ECEs), six internally SIS-covered endografts (ICEs), and six bare stents (BSs). Devices were implanted in the balloon-injured external iliac arteries (EIAs) of nine female sheep via carotid approach. Arteriograms were obtained before and after implantation and before animal sacrifice at 1, 3, and 6 months. Histologic studies of explanted specimens were performed. RESULTS: Implantation of all BSs, ECEs, and ICEs was successful, but slight luminal narrowing of 19% +/- 5.3% (range, 12%-28%) was seen in ICEs on postimplantation angiograms. At sacrifice, all six BSs and ECEs were patent, with BSs showing a mean angiographic luminal narrowing of 8.4% +/- 7.2% (range, 0%-18%) and ECEs showing a mean angiographic luminal narrowing of 16% +/- 7.5% (range, 6.5%-26%) as a result of neointimal hyperplasia. Four ICEs showed luminal narrowing of 21% +/- 17% (range, 0%-35%) as a result of marked neointimal hyperplasia and two were occluded, one at 3 months and the other at 6 months. ECEs and BSs showed approximately 80% lumen endothelialization at 1 month, which increased to 100% at 3 and 6 months. ICEs did not show complete endothelialization. CONCLUSION: The BS had the least vessel wall reaction. ECEs exhibited early endothelialization with early mild to moderate wall reaction decreasing at the late study stages. ICEs showed extensive wall reaction, possibly as a result of technical problems with SIS attachment.

Alloys↗

Lack of suitability of the rabbit model for particulate uterine artery embolization.

PURPOSE: The goal of this study was to evaluate the rabbit model for studies of particulate uterine artery embolization (UAE). Rabbits were chosen because it was believed that their year-round breeding time and short duration of pregnancy would be useful in studies of fertility and pregnancy after UAE. MATERIALS AND METHODS: Bilateral UAE was performed in 12 adult female New Zealand White rabbits weighing 4-5.2 kg. All animals were proven to be breeders before treatment. Each uterine artery was embolized to stasis with use of 180-300- microm polyvinyl alcohol (PVA) particles (n = 9 animals), 500-710- microm PVA particles (n = 1), or tris-acryl 500-700- microm gelatin microspheres (n = 2). RESULTS: Two rabbits died 7 days after embolization and the other 10 rabbits had to be killed because of malaise and weight loss 4-8 d after embolization. In all animals, necropsy demonstrated extensive uterine necrosis sparing only the tip of the uterine horn. CONCLUSION: Rabbits are an unsuitable model for studies of UAE with the embolic agents in clinical use.

Angiography↗

Percutaneous bioprosthetic venous valve: a long-term study in sheep.

A long-term evaluation of a new percutaneously placed bioprosthetic, bicuspid venous valve (BVV) consisting of a square stent and small intestinal submucosa (SIS) covering was performed in 12 sheep. Of 26 BVVs placed into the jugular veins, 25 exhibited good valve function on immediate venography and 22 on venograms obtained before the sheep were killed. Gross and histologic examination results demonstrated incorporation of remodeled and endothelialized SIS BVVs into the vein wall. Slight to moderate leaflet thickening was found mostly at their bases. Percutaneously placed SIS BVV is a promising one-way, competent valve that resists venous back-pressure while allowing forward flow.

Animals↗

Nongenomic vasodilator action of progesterone on primate coronary arteries.

In the present investigation, we test the hypothesis that progesterone can rapidly relax, via a nongenomic mechanism, persistent flow occluding, agonist-activated coronary artery (CA) vasospasm, and hyperreactive vascular muscle cell (VMC) Ca(2+) responses in ovariectomized rhesus monkeys. CA vasospasm, induced by injection of 100 microM serotonin and 1 microM U-46619 (5-HT+U; 1 ml/30 s), resulted in a decrease in CA diameter (phi) from 1.8 +/- 0.2 to 0.3 +/- 0.1 mm at the site of focal constriction. Injection of 100 ng progesterone into the CA significantly relieved the severe vasoconstriction (1.3 +/- 0.2 mm) and reestablished distal flow in 3 min; the preconstriction phi was completely restored in 8.2 +/- 2.6 min (n = 6). Similarly, cell impermeant albumin-conjugated progesterone, but not albumin-conjugated 17 beta-estradiol, decreased 5-HT+U stimulated VMC Ca(2+) responses (250 +/- 34% of basal 30 min after stimulation) back to the prestimulation level (113 +/- 17% of basal) in 25 min (half time = 7 min). The presence of a rapid vasodilator action of progesterone in the primate CA and isolated VMC suggests its benefits in hormone replacement therapy may also include nongenomic vascular relaxant actions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗