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Biomedical subjects

G E Sandusky

Publications and source records attributed to G E Sandusky.

At least 19 recordsLinked to original sources
PubMed2002

Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays.

AIMS: Using tissue microarrays, this study analysed the expression of the multidrug resistance protein, MRP2, by immunohistochemistry with two different MRP2 antibodies. This is the first study to address the expression of MRP2 in various common human neoplasms. METHODS AND RESULTS: Immunohistochemistry was performed on zinc formalin-fixed tissue to evaluate normal tissues and carcinomas using two antibodies against MRP2 (EAG5, a polyclonal antibody, and M2-lll-6, a monoclonal antibody). Immunostaining was localized in neoplastic cells mainly on the cell membrane with M2-lll-6 and cell membrane and cytoplasm with EAG5. In normal tissues MRP2 was expressed in liver, gastrointestinal tract, and kidney tubular epithelial cells with both antibodies. MRP2 was seen in nine of 22 renal cell carcinomas, eight of 13 gastric carcinomas, 25 of 49 breast carcinomas, 14 of 32 lung carcinomas, 39 of 50 colon carcinomas, and 16 of 17 ovarian carcinomas. There was < 10% variability between the two antibodies. MRP2 expression was highest in moderate to poorly differentiated tumours from colon, lung, gastric, and ovarian carcinomas and in grade 2 and 3 breast and renal carcinomas. CONCLUSION: The expression of MRP2 in many solid human tumours indicates that inherent drug resistance may play an important role as a biomarker for predictive chemotherapy treatment.

Antibodies, Monoclonal↗
PubMed2001

Protein kinase C-alpha and -epsilon modulate connexin-43 phosphorylation in human heart.

We have previously demonstrated that protein kinase C (PKC)- alpha expression is significantly elevated in failing human left ventricle, with immunostaining showing increased PKC- alpha localization at the intercalated disks of cardiomyocytes. In the present study we sought to determine, in the failing heart, if PKC- alpha interacted with connexin-43 (Cx-43) both spatially and functionally, and to compare the association of PKC- alpha/Cx-43 with that of PKC- epsilon, a PKC isozyme that does not significantly increase in failing hearts. The possibility of a PKC- alpha or PKC- epsilon/Cx-43 association in non-failing hearts was also investigated. Co-immunoprecipitation of PKC- alpha or PKC- epsilon and Cx-43 in non-failing and failing left ventricle was achieved using antibodies to PKC- alpha or Cx-43. Confocal microscopy confirmed that PKC- alpha distribution within the cardiomyocyte included co-localization with connexin-43 in both failing and non-failing myocardium. In a similar manner, confocal imaging of PKC- epsilon showed cardiomyocyte distribution in both cytosol and membrane, and colocalization of PKC- epsilon with Cx-43. Recombinant PKC- alpha or - epsilon increased PKC activity significantly above endogenous levels in the co-immunoprecipitated Cx-43 complexes (P<0.05). However, phosphorylation of purified human Cx-43 (isolated from failing human left ventricle) by recombinant PKC- alpha or PKC- epsilon resulted in only PKC- epsilon mediated Cx-43 phosphorylation. Thus, in the human heart PKC- alpha, PKC- epsilon, and Cx-43 appear to form a closely associated complex. Whereas only PKC- epsilon directly phosphorylates Cx-43, both PKC isoforms result in increased phosphorylation within the Cx-43 co-immunoprecipitated complex.

Blotting, Western↗
PubMed2001

Human truncated Smad 6 (Smad 6s) inhibits the BMP pathway in Xenopus laevis.

A previously identified truncated form of the human Smad 6 gene containing a unique 12 amino acid motif at its N-terminus was studied. We have named this truncated form of the gene Smad 6s, for 'short-form', to distinguish it from the full-length form (Smad 6fl). Reverse transcription-polymerase chain reaction and immunohistochemistry revealed that Smad 6s has a unique pattern of expression in human coronary tissue and is upregulated in diseased heart tissue. We used the expression of human Smad 6s in Xenopus laevis as a model system to assess Smad 6s function. Injection of Smad 6fl RNA (4-cell embryos, 2 x ventral) produced tadpoles with partial secondary axes. In contrast, Smad 6s RNA injected in a similar manner produced tadpoles with a severe 'head-only' phenotype with no morphological appearance of a secondary axis. Mutant Smad 6s RNA lacking the unique 12 amino acids at the N-terminus of the Smad 6s isoform produced no embryonic phenotype, suggesting that this region is important in conferring biological activity. Ectodermal explant assays show that Smad 6s has activity consistent with being a BMP antagonist and can synergize with and enhance the activities of the activin and fibroblast growth factor pathways, all of which are novel findings in this study.

Animals↗
PubMed2000

Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression.

The PTEN tumor suppressor gene is frequently inactivated in human prostate cancers, particularly in more advanced cancers, suggesting that the AKT/protein kinase B (PKB) kinase, which is negatively regulated by PTEN, may be involved in human prostate cancer progression. We now show that AKT activation and activity are markedly increased in androgen-independent, prostate-specific antigen-positive prostate cancer cells (LNAI cells) established from xenograft tumors of the androgen-dependent LNCaP cell line. These LNAI cells show increased expression of integrin-linked kinase, which is putatively responsible for AKT activation/Ser-473 phosphorylation, as well as for increased phosphorylation of the AKT target protein, BAD. Furthermore, expression of the p27(Kip1) cell cycle regulator was diminished in LNAI cells, consistent with the notion that AKT directly inhibits AFX/Forkhead-mediated transcription of p27(Kip1). To assess directly the impact of increased AKT activity on prostate cancer progression, an activated hAKT1 mutant was overexpressed in LNCaP cells, resulting in a 6-fold increase in xenograft tumor growth. Like LNAI cells, these transfectants showed dramatically reduced p27(Kip1) expression. Together, these data implicate increased AKT activity in prostate tumor progression and androgen independence and suggest that diminished p27(Kip1) expression, which has been repeatedly associated with prostate cancer progression, may be a consequence of increased AKT activity.

Animals↗
PubMed1999

Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells.

Phosphorylation of eukaryotic translation initiation factor-2alpha (eIF-2alpha) is one of the key steps where protein synthesis is regulated in response to changes in environmental conditions. The phosphorylation is carried out in part by three distinct eIF-2alpha kinases including mammalian double-stranded RNA-dependent eIF-2alpha kinase (PKR) and heme-regulated inhibitor kinase (HRI), and yeast GCN2. We report the identification and characterization of a related kinase, PEK, which shares common features with other eIF-2alpha kinases including phosphorylation of eIF-2alpha in vitro. We show that human PEK is regulated by different mechanisms than PKR or HRI. In contrast to PKR or HRI, which are dependent on autophosphorylation for their kinase activity, a point mutation that replaced the conserved Lys-614 with an alanine completely abolished the eIF-2alpha kinase activity, whereas the mutant PEK was still autophosphorylated when expressed in Sf-9 cells. Northern blot analysis indicates that PEK mRNA was predominantly expressed in pancreas, though low expression was also present in several tissues. Consistent with the high levels of mRNA in pancreas, the PEK protein was only detected in human pancreatic islets, and the kinase co-localized with somatostatin, a pancreatic delta cell-specific hormone. Thus PEK is believed to play an important role in regulating protein synthesis in the pancreatic islet, especially in islet delta cells.

Amino Acid Sequence↗
PubMed1999

Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in the failing human heart.

BACKGROUND: Increased expression of Ca2+-sensitive protein kinase C (PKC) isoforms may be important markers of heart failure. Our aim was to determine the relative expression of PKC-beta1, -beta2, and -alpha in failed and nonfailed myocardium. METHODS AND RESULTS: Explanted hearts of patients in whom dilated cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC isoform content by Western blot, immunohistochemistry, enzymatic activity, and in situ hybridization and compared with nonfailed left ventricle. Quantitative immunoblotting revealed significant increases of >40% in PKC-beta1 (P<0.05) and -beta2 (P<0.04) membrane expression in failed hearts compared with nonfailed; PKC-alpha expression was significantly elevated by 70% in membrane fractions (P<0.03). PKC-epsilon expression was not significantly changed. In failed left ventricle, PKC-beta1 and -beta2 immunostaining was intense throughout myocytes, compared with slight, scattered staining in nonfailed myocytes. PKC-alpha immunostaining was also more evident in cardiomyocytes from failed hearts with staining primarily localized to intercalated disks. In situ hybridization revealed increased PKC-beta1 and -beta2 mRNA expression in cardiomyocytes of failed heart tissue. PKC activity was significantly increased in membrane fractions from failed hearts compared with nonfailed (1021+/-189 versus 261+/-89 pmol. mg-1. min-1, P<0.01). LY333531, a selective PKC-beta inhibitor, significantly decreased PKC activity in membrane fractions from failed hearts by 209 pmol. min-1. mg-1 (versus 42.5 pmol. min-1. mg-1 in nonfailed, P<0.04), indicating a greater contribution of PKC-beta to total PKC activity in failed hearts. CONCLUSIONS: In failed human heart, PKC-beta1 and -beta2 expression and contribution to total PKC activity are significantly increased. This may signal a role for Ca2+-sensitive PKC isoforms in cardiac mechanisms involved in heart failure.

Adolescent↗
PubMed1999

Immunohistochemical localization of selected early response genes expressed in trabecular bone of young rats given hPTH 1-34.

Intermittent administration of parathyroid hormone (PTH) increases trabecular bone mass in vivo by stimulating bone formation. To further characterize the cellular and molecular mediators of the anabolic response to PTH, we examined the effect of intermittent synthetic hPTH 1-34 on the expression and localization of selected early response genes, c-fos, c-jun, c-myc, and IL-6 protein, in bone tissue by immunohistochemistry. Young male Sprague-Dawley rats, 70-100 g, were injected s.c. with 8 microg/100 g PTH or vehicle control, once daily for 5 days. Femurs were harvested 1 and 24 hours after the fifth injection, then fixed, decalcified, processed for wax embedding, and sections were immunostained. Early response genes, c-fos, c-jun and IL-6, were strongly expressed in osteoblasts, osteocytes, and megakaryocytes in bones 1 hour after PTH, when compared with vehicle-treated controls or sections from rats, 24 hours after PTH injection. Osteoblasts, osteocytes, and megakaryocytes were also positive for c-myc but the differences in stain intensity between control and treated groups were marginal. Also, scattered islands of hematopoietic cells in the marrow stained intensely for IL-6 by 1 hour after PTH, but the stain intensity decreased to control level 24 hours after the last PTH injection. Scattered islands of hematopoietic cells in the bone marrow stained more strongly for c-fos than either c-jun or c-myc, but neither localization nor stain intensity were regulated by PTH at the time points examined. We conclude that during the immediate early phase of the anabolic response, PTH regulates c-fos, c-jun, and IL-6 expression in osteoblasts, osteocytes, megakaryocytes, and selected bone marrow hematopoietic cells in bone.

Administration, Cutaneous↗
PubMed1999

Heterogeneous loss of connexin43 protein in ischemic dog hearts.

INTRODUCTION: Ischemia causes cell decoupling in the myocardium. Prolonged ischemia activates proteases and causes degradation of structural proteins as well as gap junctions. There is little information about the degradation of gap junction protein during the early time period after acute ischemia. The purpose of the present study was to investigate connexin43 (Cx43) protein degradation and distribution patterns in the canine left ventricular wall during 1 to 6 hours of ischemia. METHODS AND RESULTS: Ischemia of canine left ventricular myocardium was induced by ligation of the left anterior descending coronary artery. Following a period of in situ ischemia of up to 6 hours, samples were harvested, and standard paraffin slides were prepared for Cx43 and wheat germ agglutinin double labeling. Cx43 distribution was visualized by confocal microscopy. In controls, homogeneous distribution of Cx43 staining was determined. Ischemia caused a loss of Cx43 with a heterogeneous pattern by mixing foci of infarcted cells among normal cardiac myocytes. To determine if the changes were induced by heterogeneous reduction in the blood supply, an in vitro ischemic model was studied to induce more homogeneous ischemia. Western blot analysis of these in vitro ischemic tissue samples revealed a reduction of Cx43 protein concentration with a 50% decay time of 4.8 hours. Cx43 dephosphorylation was detected after 1 hour of in vitro ischemia. Heterogeneous loss of Cx43 was found in the in vitro ischemic tissue. There were no significant changes in Cx43 staining density during the first hour of ischemia at a time when dephosphorylation of the protein was observed. After 1 hour of ischemia, Cx43 was reduced at intercalated disk areas, and, after 6 hours, most Cx43 disappeared at intercalated disk areas, while small amounts of Cx43 remained at side-to-side junctions. CONCLUSION: Cx43 undergoes both distribution and concentration changes following acute cardiac ischemia. The loss of Cx43 protein is heterogeneous. Cx43 dephosphorylation occurred within 1 hour following ischemia.

Acute Disease↗
PubMed1996

The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice.

The MRL lpr/lpr mouse strain is an animal model for the autoimmune disorder systemic lupus erythematosus (SLE). Pathologic changes in the mice include a severe proliferative glomerulonephritis, lymph node and spleen enlargement, increase in autoantibody titers, and shortened life spans. In the present investigation, female MRL lpr/lpr mice have been dosed po daily for 7 months with the selective estrogen receptor modulator (SERM) LY139478 (4 mg/kg) or 17alpha-ethinylestradiol (EE2, 1 mg/kg) and compared to vehicle control animals. The LY139478 group had an increase in survival (73% survival at 7 months, P = 0.02) but the EE2-treated animals did not (53% survival at 7 months, P = 0.4) when compared to the control group (32% survival at 7 months). Although there were no reductions in autoantibody levels as determined by anti-DNA antibody ELISA, histological analysis of kidney tissue indicated that both LY139478 and EE2 mitigated the progression of glomerular nephritis which was evident in the controls. In contrast, there were no significant differences in lymph node size although the LY139478 and EE2 groups retained a well-defined sinusoidal region. Finally, flow cytometric analysis documented that thymuses from animals treated for 7 months with LY139478 but not with EE2 contained predominantly CD4+/CD+ T cells consistent with a normal thymic phenotype observed in non-MRL lpr/lpr mouse strains. These studies demonstrate that SERMs may be potentially useful for the treatment of autoimmune disorders.

Animals↗
PubMed1996

A family of arginal thrombin inhibitors related to efegatran.

Three new tripeptide arginal thrombin inhibitors were shown to have potent anticoagulant and antithrombotic activity: D-MePhg-Pro-Arg-H (LY287045), D-1-Tiq-Pro-Arg-H (LY294291), and D-MePhe-Pro-Arg-H (Efegatran). Efegatran and the related arginals differ mechanistically from old and from new anticoagulant agents. As illustrated with x-ray diffraction analysis of crystals of the LY294291 complex with human thrombin, the family of arginals binds thrombin with the P3, P2, and P1 residues interacting with the putative S3, S2, and S1 fibrinogen-binding sites. A hemi-acetal bond at Ser 195 was shown to contribute to the tight-binding reversible competitive thrombin inhibition properties observed with the arginal family. Tight-binding Kass values from thrombin inhibition studies correlated with thrombin clottin inhibition potency. The thrombin time (TT) assay was prolonged twofold with 33 nM Efegatran, which demonstrated an apparent Kass value of 0.8 x 10(8) L/mol (for comparison, 17 nM hirudin was required to prolong the TT assay two-fold). There are empirical anticoagulant selectivity differences between Efegatran and hirudin, manifested by large activated partial thromboplastin time (aPTT)/TT effect ratios (30 to 55) found with the arginals, as compared to the small aPTT/TT effect ratio (2 to 3) found with hirudin. The underlying anticoagulant mechanism differences between the arginals and hirudin appear to be confined to the aPTT pathway and, therefore, might involve different effects toward thrombin feedback activation of factor VIII. The arginals did not substantially inhibit other coagulation factor serine proteases. Antithrombotic effects of Efegatran and the arginal family occur at low infusion doses in dogs and appear to correlate with effects on TT without requiring perturbation of the aPTT. Selectivity properties regarding the fibrinolytic enzymes were shown to be important for successful use of the arginals in vivo as adjunctive agents during tissue plasminogen activator (t-PA) thrombolysis. The data suggest that LY287045, LY294291, and Efegatran should be expected to be useful as antithrombotic adjuncts to thrombolytic therapy with t-PA, urokinase, or streptokinase and should be expected to spare endogenous fibrinolysis. Efegatran has been evaluated in phase I clinical studies and is currently under clinical investigation in phase II protocols as a new cardiovascular anticoagulant.

Animals↗
PubMed1996

Pulmonary and mediastinal metastases of a vaccination-site sarcoma in a cat.

Sarcomas at vaccination sites in cats were first reported in 1992. Recent retrospective studies have confirmed an association between these vaccination-site sarcomas (VSS) and feline leukemia virus (FeLV) and/ or rabies vaccines. In most cases, VSS are locally invasive fibrosarcomas that tend to recur but rarely metastasize. We report the mediastinal and pulmonary metastases of a VSS in a FeLV-and feline immunodeficiency virus-negative, 8-year-old, domestic short-haired cat. The primary sarcoma was removed from an interscapular vaccination site and diagnosed as a VSS 3 months prior to radiographic lesions suggestive of pulmonary and mediastinal metastases. At necropsy, there were multiple pulmonary and mediastinal nodules that histologically and ultrastructurally were fibrosarcomas, cytomorphologically similar to the VSS. In addition, immunohistochemical staining patterns of the VSS and metastatic sites were consistent with that described for VSS. Recent reports of pulmonary and mediastinal metastases of interscapular VSS emphasize the importance of early diagnosis and treatment of these tumors.

Animals↗
PubMed1995

Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: effects on restenosis and implications for catheter-based drug delivery.

OBJECTIVES: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. BACKGROUND: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. METHODS: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). RESULTS: Delivery of efficiency was 0.01% and intramural retention < 24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicine resulted in toxicity to the adjacent musculature. CONCLUSIONS: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

Animals↗
PubMed1995

Ependymoma of the neurohypophysis and hypernatremia in a horse.

A 2-year-old Standardbred gelding was examined because of prolapse of the third eyelid; myoclonus of the muscles of the head, neck, and forelimbs; and persistent tail swishing. The horse had a high plasma sodium concentration but was not drinking water. The hypernatremia could not be corrected by means of IV administration of fluids, and the horse became worse and, 6 days later, died. At necropsy, a tumor was found to be compressing the neurohypophysis and the area in the brain in which the thirst centers are believed to be located. It is believed that hypernatremia in this horse was a result of altered thirst.

Animals↗
PubMed1995

Healing comparison of small intestine submucosa and ePTFE grafts in the canine carotid artery.

Continuing investigation of small-diameter vascular graft materials suggests that unacceptable graft complications continue and that the ideal material has not yet been found. We compared healing of xenogeneic small diameter grafts (3.5 to 5.0 mm diameter) made from porcine small intestine submucosa (SIS) implanted in the carotid artery to expanded polytetrafluorethylene (ePTFE) in the contralateral carotid in 8 dogs. Two dogs were sacrificed for graft evaluation at 7, 28, 90, and 180 days after surgery. Only one SIS graft was occluded at 28 days and the other 7 were patent. Six of 8 ePTFE grafts were occluded with thrombi. One was patent at 7 and one at 90 days. At 7 days post-implant, the luminal surface of the SIS graft was covered by a thick (30 microns), compact fibrin meshwork. By 28 days endothelial cells were seen completely covering the fibrin meshwork which stained for FVIII-related antigen. Smooth muscle cells were observed in the neo-intima. Most ePTFE grafts had fibrin on the luminal surface which formed fibrin thrombi with platelets and numerous red blood cells. Complete endothelial coverage of the ePTFE grafts was not observed by 180 days. There was not a pronounced neointima seen on the luminal surface of the graft. The vasa vasorum was present in the fibrous capsule surrounding the ePTFE graft, but it did not penetrate into the graft as seen in the SIS graft. At 90 days the SIS vascular graft had the histological appearance similar to a normal artery. The SIS graft potency and healing characteristics were superior to the synthetic ePTFE graft and warrant further investigation.

Animals↗
PubMed1993

Coronary artery toxicity in beagle dogs given indolidan, a type III phosphodiesterase inhibitor.

The hemodynamic changes and cardiovascular lesions produced by a single iv dose of 2.0 mg/kg indolidan were evaluated in four beagle (two male, two female) dogs. Four additional dogs (two male, two female) served as vehicle controls. This was followed by a multidose study in which the same dose of indolidan or vehicle was given iv to dogs (4/group) on 4 consecutive days. Both studies were followed for 4 days postdose before termination. Clinical signs, mean arterial blood pressure, and heart rate were evaluated. Seven sections of the heart, approximately 25 sections of the coronary arteries, and 3 sections of the carotid, subclavian, spermatic or ovarian, renal, and femoral arteries were examined. Mean blood pressure was decreased 20 to 25% over a 24-hr period and heart rates were increased 40 to 50% after treatment and remained elevated for at least a 24-hr period in both single and multidose treated groups. The earliest lesions occurred in three of four treated dogs after a single intravenous dose of 2.0 mg/kg. The main lesion was sporadic in distribution and seen in the outer one-half of the smooth muscle media of the coronary arteries. Smooth muscle degeneration and necrosis were present, with little secondary inflammation. No lesions were observed in the peripheral arteries or the myocardium. The coronary arterial lesions observed after the multidose study were more extensive and severe. The lesions were seen in large extramural and large intramural coronary arteries. These were characterized by marked smooth muscle necrosis involving most of the media, destruction of the internal elastic membrane, and marked adventitial fibroplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

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.

Animals↗
PubMed1992

Histologic findings after in vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid artery in dogs.

A small caliber vascular graft from porcine small intestine submucosa (SIS) was implanted in a canine carotid artery (n = 24) and compared with an autogenous saphenous vein graft that was implanted in the contralateral carotid artery. In this study, four grafts were evaluated at the following times after surgery: 2, 7, 14, 28, 90, and 180 days. One SIS graft thrombosed at 2 days, two SIS and two saphenous vein grafts were thrombosed at 90 days, and one SIS and one saphenous vein graft were thrombosed at 180 days. At 2 days after implant, the luminal surface of the SIS graft was covered by a thin (30 mu) fibrin meshwork. By 14 days after surgery, endothelial cells on the fibrin meshwork were staining for FVIII-related antigen. Smooth muscle cells were observed in the new intima (fibrin meshwork) by 28 days. At 90 days, both types of graft had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis. Similar histology was observed at 180 days. These results indicate that this SIS graft was similar to saphenous vein graft in the dog.

Animals↗