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At least 595 records · Page 33Linked to original sources

PubMed2003

Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors.

Often described as incomplete or absent, the basement membrane of blood vessels in tumors has attracted renewed attention as a source of angiogenic and anti-angiogenic molecules, site of growth factor binding, participant in angiogenesis, and potential target in cancer therapy. This study evaluated the composition, extent, and structural integrity of the basement membrane on blood vessels in three mouse tumor models: spontaneous RIP-Tag2 pancreatic islet tumors, MCa-IV mammary carcinomas, and Lewis lung carcinomas. Tumor vessels were identified by immunohistochemical staining for the endothelial cell markers CD31, endoglin (CD105), vascular endothelial growth factor receptor-2, and integrin alpha5 (CD49e). Confocal microscopic studies revealed that basement membrane identified by type IV collagen immunoreactivity covered >99.9% of the surface of blood vessels in the three tumors, just as in normal pancreatic islets. Laminin, entactin/nidogen, and fibronectin immunoreactivities were similarly ubiquitous on tumor vessels. Holes in the basement membrane, found by analyzing 1- micro m confocal optical sections, were <2.5 micro m in diameter and involved only 0.03% of the vessel surface. Despite the extensive vessel coverage, the basement membrane had conspicuous structural abnormalities, including a loose association with endothelial cells and pericytes, broad extensions away from the vessel wall, and multiple layers visible by electron microscopy. Type IV collagen-immunoreactive sleeves were also present on endothelial sprouts, supporting the idea that basement membrane is present where sprouts grow and regress. These findings indicate that basement membrane covers most tumor vessels but has profound structural abnormalities, consistent with the dynamic nature of endothelial cells and pericytes in tumors.

Animals↗

PubMed2001

Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications.

The formation of coronary collateral vessels is a compensatory mechanism secondary to repetitive or chronic myocardial ischemia. During the past three decades the functional and prognostic benefit of such collateral vessels has been established. There are large interindividual differences in the number and extent of collateral vessels that may be explained by differences in the anatomic situation or by differences in the individual capacity to develop functional collateral vessels. Diabetes mellitus has recently been identified as one of the first negative predictors of collateral vessel formation. Novel molecular approaches have helped to improve our understanding of the process of collateral vessel formation in recent years. Besides the process of true angiogenesis, i.e. the formation of new capillaries out of preexisting ones, the formation of a collateral circulation is largely based on the growth of preexisting arterioles (collateral vessels or anastomoses) named arteriogenesis. One important feature of arteriogenesis is the infiltration of monocytes into the growing collateral vessel. Our group shows that the ability of monocytes to migrate towards a gradient of VEGF-A is severely impaired in diabetic individuals, and this impaired response seems to be secondary to a signal transduction defect within the monocyte. In this review the pathophysiology of diabetes-related monocyte dysfunction and the potential role of VEGF-A in collateral vessel formation are discussed.

Aged↗

PubMed1997

Actions of diaspirin cross-linked hemoglobin on isolated rat and dog vessels.

The objectives of these studies were to investigate the responses of isolated blood vessels from rats and dogs to the administration of diaspirin cross-linked hemoglobin (DCLHb) and to determine the mechanisms of these responses. Isolated vascular rings (3 to 5 mm) were suspended at optimal passive tension in Krebs-filled (37 degrees C) tissue baths and bubbled with 95% O2-5% CO2, and isometric tension was recorded. With the vessels under basal conditions increasing concentrations of DCLHb (10(-8)-3 x 10(-6) mol/L) were added. DCLHb addition was repeated during a submaximal contraction with norepinephrine and again during acetylcholine relaxation. The effects of the nitric oxide synthase inhibitor L-nitro arginine (10(-5) mol/L) on the responses to DCLHb were also determined. Dog vessels developed very little tension (1% to 5% of norepinephrine maximum), whereas rat arteries contracted between 9% and 15% when exposed to DCLHb under basal conditions. However, both the dog and rat vessels developed significant tension to DCLHb when they were precontracted (5% to 54%) and also when they were relaxed with acetylcholine (21% to 93%). L-nitro arginine eliminated the contractile responses to DCLHb but did not cause contraction of any of the vessels under basal conditions. We conclude that in this model the mechanism of DCLHb-induced contractions of in vitro dog and rat vessels is dependent on interference with nitric oxide. This is similar to the mechanism of DCLHb action in isolated pig vessels reported previously. Differences in responses of dog, rat, and pig vessels under basal conditions in vitro are the result of active generation of nitric oxide by pig but not by dog or rat vessels.

Acetylcholine↗

PubMed2003

Application of electric field stimulation for investigations of human placental blood vessels.

OBJECTIVE: To test electric field stimulation on human placental vessels. METHODS: The effects of electric field stimulation on placental vessels were examined in an isometric myograph. RESULTS: Electric field stimulation induced contractions in human placental blood vessels in vitro under isometric conditions when bubbling carbogen through the organ bath. After reaching half-maximal contractions, the vessel rings showed spontaneous relaxation. Pretreatment with verapamil (10(-6) mol/L) or nickel (Ni(2+)) (2 mmol/L) inhibited the contractions to a magnitude of 63.81% +/- 7.69% and 88.36% +/- 12.17% (mean +/- standard error of the mean), respectively. In calcium (Ca(2+))-free medium after combined cyclopiazonic acid (10(-5) mol/L) and Ni(2+) treatment, it was not possible to elicit contractions with electric field stimulation. Bubbling through physiologic in utero hypoxic gases enhanced the contractile responses of the human placental vessel rings to electric field stimulation. The spontaneous relaxation of the veins was not altered, but those of the arteries were reduced to zero. Testing the same gases on mesenteric arteries of rats had an opposite effect concerning contractility. Sodium nitrite decreased the contractions of the placental vessel rings, but the efficacy was decreased by the in utero gases. CONCLUSION: Electric field stimulation has a direct, non-neurogenic contractile effect on isolated placental vessels, which mainly depends on the influx of extracellular Ca(2+) and on a mechanism independent of intracellular Ca(2+) concentration elevation. Physiologic hypoxia has a stimulatory effect on the contractility of human placental vessels, therefore in utero gases should be used instead of carbogen gas; and electric field stimulation is a suitable method for the investigation of the direct effects of pharmacologic agents on human placental vessels.

Adult↗

PubMed1995

Flow patterns and preferred sites of intimal thickening in end-to-end anastomosed vessels.

BACKGROUND: Fluid mechanical factors are suspected to be involved in the pathogenesis and localization of intimal hyperplasia in anastomosed vessels. However, no direct correlation has been established between the flow and the exact sites of intimal hyperplasia. Hence we have studied the relationship between the flow and preferred sites of wall thickening in 90-degree- and 45-degree-cut and end-to-end anastomosed vessels. METHODS: Twenty-five 90-degree and twenty-five 45-degree end-to-end anastomoses were performed on the femoral arteries of 17 adult mongrel dogs. The vessels were harvested at 3 months after operation, fixed at 100 mm Hg, dehydrated with ethanol, and rendered transparent by immersing them in methyl salicylate. Exact locations and sizes of intimal thickening and characteristics of the flow prevailing at sites of anastomoses were studied in detail by means of flow visualization and cinemicrographic techniques. RESULTS: It was found that a perfect correlation exists between the preferred sites of intimal thickening and the regions of slow recirculation flows with low wall shear stresses. In both 90-degree and 45-degree anastomosed vessels, intimal thickening developed only in those vessels in which formation of slow recirculation flows was observed. It was also found that although a pronounced and localized intimal thickening developed in 45-degree anastomosed vessels, the degree of circumferential constriction caused by both surgical procedures and development of intimal thickening was much milder in 45-degree than 90-degree anastomosed vessels. CONCLUSIONS: The results suggest that key hemodynamic factors involved in the localization of intimal thickening in end-to-end anastomosed vessels are low velocity of flowing blood and the resultant low shear stresses acting on the vessel wall.

Anastomosis, Surgical↗

PubMed2003

Helical computed tomography for identification of crossing vessels in ureteropelvic junction obstruction-comparison with operative findings.

OBJECTIVES: To evaluate the use of contrast-enhanced helical computed tomography (HCT) scanning with three-dimensional reconstructions as a possible identifier of crossing vessels in ureteropelvic junction (UPJ) obstruction. Endoscopic treatment of UPJ obstruction has a success rate that approaches 90%. These results drop to 40% in the presence of crossing vessels. Unrecognized crossing vessels can also result in significant hemorrhage during endopyelotomy. The presence of crossing vessels is, for many, an indication for open or laparoscopic UPJ repair. Therefore, accurate preoperative imaging is crucial for appropriate treatment planning. METHODS: Our study population consisted of 18 patients evaluated and treated for UPJ obstruction at the University of Michigan Health System. These patients underwent routine contrast-enhanced preoperative HCT scanning before UPJ repair. A prior history of failed endoscopic treatment, patient preference, and HCT findings of crossing vessels were indications for open or laparoscopic repair. The imaging findings were compared with open findings during laparoscopic or open pyeloplasty. RESULTS: An HCT finding of the presence of crossing vessels was a significant positive predictor, with a value of 100%. The sensitivity in this population was 91% and the specificity was 100%. No difference was noted between the detection of arterial or venous crossing vessels. The positive predictive value was 100%, and the negative predictive value was 88%. CONCLUSIONS: HCT is an accurate predictor of the presence of crossing vessels in UPJ obstruction. Because crossing vessels may have a profound impact on treatment outcome, HCT can serve as an effective, noninvasive, preoperative screening tool.

Adult↗

PubMed2000

The effects of beam shape on the ability to predict changes in vessel size from Doppler signal power.

Theory suggests that, under certain ideal circumstances, the power of a Doppler signal is proportional to the size of the vessel from which it is recorded and can, therefore, be used to assess the scale of any changes in vessel size that occur during clinical recordings of cerebral blood flow. However, the relationship between signal power and vessel size depends on the intensity of the incident beam being uniform across the vessel. This is unlikely to be the case for cerebral vessels insonated by commercial transducers. A model was used to estimate the signal power received from vessels insonated by a beam passing through a homogeneous medium, and also by beams passing through each of five samples of temporal bone. In each case, the effects of initial vessel size and various changes in cross-sectional area were investigated for different vessel positions in the beam. The results for the beam paths through bone predict that the power change arising from a change in vessel cross-sectional area is between 5% and 75% smaller than that occurring in a uniform beam. If these results are representative of those arising for an in vivo change in middle cerebral artery size, then the potential magnitude of the error illustrates the caution that may need to be applied when interpreting changes in Doppler signal power.

Adult↗

PubMed1998

Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma.

Angiogenesis is essential for growth and metastasis of solid malignancies. In several tumours, tumour vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. To determine if vessel count and VEGF expression are prognostic factors in pancreatic cancer, we examined these parameters in resected tumour specimens from 22 patients who did not receive pre-operative therapy. Paraffin-embedded tumour specimens were immunohistochemically stained for factor VIII (surrogate for vessels) and VEGF. Vessel counts and VEGF expression were evaluated without knowledge of patient outcome. The median follow-up for the entire group had not been reached as of 23.1 months (range 10-69 months). The mean vessel count and VEGF expression were no different between those patients who had recurrences and those who did not. By linear regression analysis, the correlation of VEGF expression with vessel count did not reach statistical significance (P = 0.0685). Survival and time to recurrence were similar in patients with high and low vessel counts and VEGF expression of 1, 2 or 3. Tumour differentiation or lymph node positivity had no effect on either VEGF expression or vessel count. Our data suggest that, in contrast to findings in other solid malignancies, vessel count and VEGF expression are not predictors of survival or recurrence in patients with resectable adenocarcinoma of the pancreas.

Adenocarcinoma↗

PubMedDate not supplied

Accuracy of DSA in the evaluation of patency of infrapopliteal vessels.

PURPOSE: To evaluate the accuracy of intraarterial digital subtraction angiography (DSA) in the demonstration of patent infrapopliteal vessels. PATIENTS AND METHODS: One-hundred sixty-five arteriograms were obtained in 153 consecutive patients prospectively enrolled to evaluate lower extremity ischemia. In 86 cases a follow-up angiogram of the infrapopliteal vessels was obtained during surgery or after endovascular intervention (n = 57). Twenty-nine arteriograms were followed by surgical exploration of the infrapopliteal vessels. Standard angiographic technique was performed with intraarterial DSA of the most symptomatic foot. Visualization of distal vessels was compared with intraoperative or postintervention imaging or with the results of surgical exploration. RESULTS: Of the 57 procedures after which either intraoperative or post-endovascular intervention angiography was performed, DSA results were equivalent in 47 (82%) and worse in five (9%). When individual vessels were evaluated, the sensitivity of DSA in the identification of patent named vessels was 95%, and the specificity was 92%. Among 29 cases with a surgical standard of reference, 28 patients underwent bypass to a vessel correctly identified as patent at DSA; one patient was incorrectly identified as having no patent named vessels. CONCLUSION: Intraarterial DSA is accurate and reliable in the assessment of patency in infrapopliteal vessels before surgery or endovascular intervention in patients with infrainguinal atherosclerotic disease.

Adult↗

PubMed1999

Sustained vessel dilation induced by increased pulsatile perfusion of porcine carotid arteries in vitro.

Arterial pulse pressure (PP) increases with exertional stress and ageing, and can modify vessel diameter in smaller vessels. To test if PP must exceed a certain range to influence vessel diameter, and determine if such effects are endothelium-dependent or intrinsic to vascular viscoelasticity, eight fresh excised porcine carotid artery segments were perfused with modified Krebs-Henseleit by a servo-controlled system generating physiological arterial pressure waveforms. In a separate group of vessels (n = 10), the endothelium was mechanically removed. Vessel external diameter was measured by video edge-detection. Vessels partially preconstricted with noradrenaline were perfused at 9 mL min(-1) mean flow, at mean pressure of 90 or 120 mmHg, and zero PP. PP alone was then increased to 40, 70, or 120 mmHg at 1 Hz cycling rate for 5 min, then returned to zero and vessel diameter measured immediately thereafter. The protocol was repeated after 10-20 min stabilization. Mean vessel diameter rose proportionally with PP only once PP exceeded 40 mmHg, with maximal increases of 6-9% at a PP of 120 mmHg. Similar responses were obtained in vessels with and without a functional endothelium, at both mean pressures. Thus, when exposed to higher than normal resting PP, conduit arteries dilate owing to the stress-relaxation response of their viscoelastic wall. This mechanism of PP-mediated vascular dilatation may contribute to enhanced organ perfusion when small resistance arteries are already dilated.

Animals↗

PubMed2000

Use of helical CT in assessment of crossing vessels in pelviureteric junction obstruction.

AIM: The purpose of this study is to confirm the accuracy of non-invasive helical computed tomography (CT) with multiplanar reformatting in the diagnosis of crossing vessels in patients with pelviureteric junction (PUJ) obstruction. MATERIALS AND METHODS: Nineteen patients with confirmed PUJ obstruction underwent CT of the renal area with intravenous contrast medium. Patients shown to have crossing vessels had to undergo a pyeloplasty by open surgery or laparoscopy. Patients with no vessels could have their PUJ obstruction safely treated with less invasive techniques such as balloon dilatation. RESULTS: Fourteen patients were shown to have crossing vessels. Of these, 10 had their relationship to the PUJ confirmed at a subsequent laparotomy. Of the remaining four patients, one was lost to follow-up and two were unwell due to unrelated disease. The other patient had already had a vessel moved at a previous laparotomy. Of the five patients without obstructing vessels, two were confirmed not to have a related vessel at laparotomy, one has undergone balloon dilatation and the other two were lost to follow-up. CONCLUSION: Helical CT is an accurate and non-invasive method of demonstrating crossing vessels in PUJ obstruction. Diagnosis of these vessels has a major role in the choice of therapeutic treatment.

Adolescent↗

PubMed1991

[Differences in blood flow in maternal blood vessels in normal pregnancies and gestosis].

Clinical studies showed a lower blood flow in renal und uterine vessels in gestotic pregnancies. A comparison was therefore made between three maternal vessels (uterine, renal und thyroideal vessels) in normal and gestotic pregnant and non-pregnant women to show if the higher vessel resistance in gestotic pregnancies is a local or systemic event. There was a significant difference between the collectives in the blood flow of renal and uterine vessels, but no difference between the resistance in thyroideal vessels. The difference in the blood flow of renal vessels was higher than the difference in uterine vessels in the pregnant women. The increasing resistance, therefore, seems to be a local event at the beginning of the gestotic pattern of signs and symptoms. The higher resistance in the renal vessels allows, the conclusion that the kidney might be the important organ in the origin of the gestotic pattern of signs and symptoms.

Adult↗

PubMed2002

Role of target vessel size and body surface area on outcomes after percutaneous coronary interventions in women.

BACKGROUND: Women have higher mortality rates than men after coronary angioplasty. Differences in target vessel size may partially account for these differences. We set out to explore the effects of sex, body surface area (BSA), and target coronary vessel size on clinical outcomes after angioplasty. METHODS: Data from 5 interventional trials and 1 registry were pooled for analysis (n = 3982). RESULTS: Compared with men, women undergoing angioplasty were older, had lower weights and BSA, more coronary risk factors, and slightly smaller target coronary vessel size (as assessed by reference vessel diameter). The correlation between target vessel size and BSA was poor (r = 0.13). At 6 months, women had higher mortality rates (1.7% vs 0.8%, P =.03) but similar rates of myocardial infarction and repeat revascularization. On univariate analysis, advanced age, smaller BSA, and female sex were associated with increased mortality, but target vessel size was not. Advanced age was the only significant multivariate predictor of mortality. Target vessel size and diabetes were independent predictors of repeat revascularization. CONCLUSIONS: Women have higher unadjusted 6-month mortality rates after angioplasty, owing largely to their more advanced age at the time of intervention. Smaller target vessel size is associated with increased risk of restenosis and repeat revascularization; however, it does not appear to be a predictor for downstream mortality. As such, the fact that women have smaller vessels does not account for their higher 6-month mortality after coronary angioplasty.

Aged↗

PubMed2001

Inducible change in the behavior of resistance arteries from circulating factor in preeclampsia: an effect specific to myometrial vessels from pregnant women.

OBJECTIVE: It has previously been observed that a circulating factor or factors may be responsible for the changes in vessel behavior that are postulated to underlie the pathogenesis of preeclampsia. We wished to ascertain whether such changes in endothelial function are dependent on the vascular bed under investigation. STUDY DESIGN: Myometrial and infracolic omental vessels resistance vessels were obtained at cesarean delivery or hysterectomy. After incubation with either plasma from women with preeclampsia or plasma from normotensive pregnant women, myographic techniques were used to assess the endothelium-dependent relaxations of these vessels. RESULTS: Incubation of myometrial vessels from normotensive pregnant women with plasma from women with preeclampsia resulted in a significant reduction in endothelium-dependent relaxation, an effect that was independent of the parity of the patients from whom the vessels had been taken. Incubation of omental vessels from normotensive pregnant women and myometrial vessels from nonpregnant women with plasma from women with preeclampsia had no effect on the endothelium-dependent relaxation observed. CONCLUSIONS: This study demonstrates that the inducible changes in resistance vessel behavior are dependent on the tissue bed under investigation and on the pregnancy status of the patient.

Adult↗

PubMed1999

Failed endopyelotomy: low expression of TGF beta regardless of the presence or absence of crossing vessels.

BACKGROUND AND OBJECTIVE: Endopyelotomy relies on Davis' intubated ureterotomy principle of healing by secondary intention and smooth-muscle regeneration. Approximately 15% of endopyelotomies fail, and the restrictured segment almost always shows evidence of reactive fibrosis with little smooth-muscle regeneration. Previous data suggests that an elevation of TGF beta in obstructed ureteropelvic junctures may be necessary for successful tissue repair following endopyelotomy. The role of crossing vessels in endopyelotomy failure is very controversial. To better understand the pathophysiology of endopyelotomy failure, the expression of transforming growth factor-beta (TBG beta) in patients with a failed endopyelotomy and crossing vessels was compared with that in patients without crossing vessels, as well as those having primary pyeloplasty or a normal ureteropelvic junction (UPJ). MATERIALS AND METHODS: The expression of TGF beta was detected immunohistochemically in slide-mounted thin sections (4 microns) cut from paraffin-blocked adult UPJ segments obtained during primary pyeloplasty (N = 11), secondary pyeloplasty after failed endopyelotomy with documented crossing vessels (N = 10), secondary pyeloplasty after failed endopyelotomy without crossing vessels (N = 11), and normal UPJs removed during nephrectomy for purposes unrelated to obstruction (N = 11). Expression was graded on a scale of 0 to 4. RESULTS: The combined failed endopyelotomy group had a significantly (P < 0.05) lower level of TGF beta (1.9 +/- 0.7) than did primary obstructed UPJs (2.6 +/- 0.7). The TGF beta level in the crossing vessels group (1.9 +/- 0.7) did not differ from that in the group without crossing vessels (1.8 +/- 0.7), nor did it differ from that in the group with normal UPJs (1.6 +/- 0.7). As expected, primary obstructed UPJs had a significantly higher level of TGF beta than normal ones (P < 0.02). CONCLUSIONS: Obstructed UPJs that had failed endopyelotomy had a similarly reduced level of TGF beta whether or not crossing vessels were present. These data suggest that an elevation of TGF beta in obstructed UPJs may be necessary for successful tissue repair after endopyelotomy and that the presence of crossing vessels is probably not relevant.

Adult↗

PubMed1985

Effect of felodipine on resistance vessels from spontaneously hypertensive and normotensive rats.

We have investigated the effect of felodipine [4-(2,3,-dichlorophenyl)-1,4-dihydro-2, 6-dimethyl-3-ethoxycarbonyl-5-ethoxycarbonylpyridine] on the calcium concentration response relations of noradrenaline-activated mesenteric resistance vessels from 3-mo-old spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats. SHR vessels were more sensitive to calcium (ED50 approximately equal to 5.49 X 10(-5) M) than WKY vessels (ED50 approximately equal to 1.01 X 10(-4) M) in control condition. Also, maximal active tension development in SHR vessels was greater (3.14 N/m) than in WKY vessels (2.22 N/m). Felodipine (10(-12) M) decreased calcium sensitivity in vessels from both strains and also decreased maximal active tension development of SHR vessels. In a higher concentration (5 X 10(-10) M), the calcium sensitivity of both SHR and WKY vessels became similar. The active tension development was equally reduced in both rat strains. The results indicate that at least part of the antihypertensive effect of felodipine is due to a direct vasodilation, and also that vessels from SHRs may be more sensitive to felodipine than those from WKY rats.

Animals↗

PubMed1999

Algorithm for recipient vessel selection in free tissue transfer to the lower extremity.

The proper selection of a recipient vessel is essential for the success of free tissue transfer, especially when the transfer is to the lower extremity. However, a general agreement on which vessel to use has not been reached yet. Conflicting data have been reported on the survival and outcome of the transferred flaps, depending on the vessel used or the location of anastomosis. The aim of this study was to identify the patterns and problems in the selection of recipient vessels for free tissue transfer to the lower extremity and to establish a general guideline for proper selection. From September of 1990 to December of 1997, 50 consecutive, microvascular, free tissue transfers were performed on the lower extremity. The causes requiring soft-tissue coverage included trauma (25), unstable scar (11), chronic osteomyelitis (7), and tumors (7). The mean follow-up period was 22.4 months (range, 2 to 41 months). In 25 cases, the posterior tibial vessel was used as the recipient vessel. The microvascular anastomosis was done proximal to the zone of injury in 45 cases. The two most important factors in the selection of a recipient vessel are the site of injury and the vascular status of the lower extremity. Less important factors include the flap to be used, method, and site of microvascular anastomosis. All the currently feasible options for recipient vessels are included, and the opinions of other surgeons are reviewed. A general guideline is established, and an algorithm for the proper selection of a recipient vessel is proposed. This algorithm is a fast and convenient guide for evaluating the wound and planning the free flap to the lower extremity.

Adolescent↗

PubMed2002

Increased nerve and blood vessel ingrowth associated with proteoglycan depletion in an ovine anular lesion model of experimental disc degeneration.

STUDY DESIGN: Nerves and blood vessel distribution in discs were localized immunohistochemically and correlated with the proteoglycan contents of normal and degenerate disc tissues. OBJECTIVE: The aim of the present study was to systematically evaluate whether nerve and blood vessel ingrowth was associated with depletion of disc proteoglycans and degenerative changes in an established experimental model of disc degeneration. SUMMARY OF BACKGROUND DATA: Animal models of disc degeneration, allowing longitudinal study of pathogenic mechanisms, are limited. The ovine model enables systematic monitoring of blood vessel and nerve ingrowth during the development of disc degeneration after injury to the anulus fibrosus. METHODS: Merino sheep received a controlled left anterolateral surgical defect in the outer anulus fibrosus of the L1-L2 and L3-L4 discs (lesion group); sham-operated controls received the retroperitoneal anterolateral approach only. Animals were killed 3, 6, 12, and 26 months postoperation, and the discs were collected for histology and compositional and morphologic analyses. Sagittal tissue sections were stained with toluidine blue and hematoxylin and eosin; Type IV collagen immunolocalization visualized blood vessel ingrowth, and nerves were immunolocalized using monoclonal antibodies to growth-associated protein (GAP-43), protein gene product 9.5, and glial fibrillary acidic protein. RESULTS: Compositional and histologic results demonstrated early focal depletion 3-12 months postoperation of glycosaminoglycan associated with lesion development, increased blood vessel and nerve ingrowth, and infiltration of cells from the outer anulus fibrosus along the plane of the original defect. Blood vessel numbers in the outer to mid third of the anulus fibrosus were elevated in the lesion discs 3-6 months postoperation reaching a maximum at 12 months postoperation; nerves immunoreactive with protein gene product 9.5 (also maximal at 12 months postoperation) were often found associated (but not exclusively) with blood vessels, and some nerves were also reactive with GAP-43 and glial fibrillary acidic protein, but only at 12 months postoperation. CONCLUSIONS: Nerve and blood vessel ingrowth into the anulus fibrosis were strongly associated with proteoglycan depletion. The ovine anular lesion model of disc degeneration is a useful experimental model for the systematic evaluation of nerve and blood vessel development after anular injury.

Animals↗