A comprehensive histopathological evaluation of vascular medial fibrosis: Insights into the pathophysiology of arterial stiffening

Selvin, Elizabeth; Najjar, Samer S.; Cornish, Toby C.; Halushka, Marc K.

doi:10.1016/j.atherosclerosis.2009.06.025

Cited by 58 publications

(61 citation statements)

References 27 publications

(22 reference statements)

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“…Digital images of the entire anal canal cross section (muscle and mucosa) were captured. The image analysis was performed to quantify connective tissue/collagen and skeletal muscle components (Nikon NIS Elements, Melville, NY) (24). Briefly, the amount of fibrosis formation on the injured and contralateral side was measured by selecting two representative and nonadjacent sections and photographing up to three microscopic fields.…”

Section: Methodsmentioning

confidence: 99%

Myoarchitectural and functional alterations in rabbit external anal sphincter muscle following experimental surgical trauma

Rajasekaran

Sinha

Seo

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Rajasekaran MR, Sinha S, Seo Y, Salehi M, Bhargava V, Mittal RK. Myoarchitectural and functional alterations in rabbit external anal sphincter muscle following experimental surgical trauma. Am J Physiol Gastrointest Liver Physiol 307: G445-G451, 2014. First published July 3, 2014; doi:10.1152/ajpgi.00450.2013.-Obstetrical trauma to external anal sphincter (EAS) is extremely common; however, its role in the development of anal incontinence is not clear. We examined the regenerative process and functional impact of experimental surgical trauma to EAS muscle in an animal model. Surgical myotomy, a craniocaudal incision extending along the entire length and thickness of the EAS, was performed in rabbits. Animals were allowed to recover, and anal pressures were recorded at weekly intervals for 12 wk using a custom-designed probe system to determine the length-tension property of EAS muscle. Animals were killed at predetermined time intervals, and the anal canal was harvested for histochemical studies (for determination of muscle/connective tissue/ collagen) and sarcomere length measurement. In addition, magnetic resonance diffusion tensor imaging (MR-DTI) and fiber tracking was performed to determine myoarchitectural changes in the EAS. Myotomy of the EAS muscle resulted in significant impairment of its length-tension property that showed only partial recovery during the 12-wk study period. Histology revealed marked increase in the fibrosis (connective tissue ϭ 69% following myotomy vs. 28% in controls) at 3 wk, which persisted at 12 wk. Immunostaining studies confirmed deposition of collagen in the fibrotic tissue. There was no change in the sarcomere length following myotomy. MR-DTI studies revealed disorganized muscle fiber orientation in the regenerating muscle. We conclude that, following experimental injury, the EAS muscle heals with an increase in the collagen content and loss of normal myoarchitecture, which we suspect is the cause of impaired EAS function. length-tension; fibrosis; magnetic resonance diffusion tensor imaging FECAL INCONTINENCE (FI) is extremely common and reported by 7-10% of women over 60 years of age (1, 3, 4). Childbirthrelated injury to the muscles of the anal sphincter complex is a possible cause of FI in women (11,26). The injury to these muscles occurs through several mechanisms. First is the stretch of the muscles caused by the fetus during its passage through the birth canal. Second is the trauma related to instrumentation, and third is surgical episiotomy. Women who sustain thirddegree obstetrical tear develop FI soon after delivery if muscles are not properly repaired (13). However, in the significant majority of women, injury to the anal sphincter and other pelvic floor muscle is occult. Symptoms develop in the fifth to sixth decade of life, the reasons for which are not clear.Of the three components of the anal sphincter complex [the internal anal sphincter, external anal sphincter (EAS), and puborectalis muscle (PRM)], it is generally believed that EAS muscle plays a significan...

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Section: Methodsmentioning

confidence: 99%

Myoarchitectural and functional alterations in rabbit external anal sphincter muscle following experimental surgical trauma

Rajasekaran

Sinha

Seo

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…A multivariate regression analysis showed an association between renal dysfunction and the magnitude of medial fibrosis in postmortem vascular fragments from 100 patients (32). Arterial medial fibrosis was associated with older age and diabetes in a pilot study of 50 patients with CKD undergoing AVF creation.…”

Section: Medial Fibrosis and Avf Outcomesmentioning

confidence: 99%

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

Vázquez-Padrón

Allon

2016

CJASN

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Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.

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“…The tissue images were analyzed (C.T.S., M.K.H.) by using automated open-source image analysis software (FrIDA; Johns Hopkins Medical Institutions, Baltimore, Md) (14) to measure the total area of fibrotic tissue and myocardium in each sample. Endocardial and perivascular regions were excluded from analysis as nonrepresentative to maintain consistency with prior reports (13).…”

Section: Endomyocardial Biopsymentioning

confidence: 99%

T1 Mapping in Cardiomyopathy at Cardiac MR: Comparison with Endomyocardial Biopsy

Sibley¹,

et al. 2012

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Purpose:To determine the utility of cardiac magnetic resonance (MR) T1 mapping for quantification of diffuse myocardial fibrosis compared with the standard of endomyocardial biopsy. Materials and Methods:This HIPAA-compliant study was approved by the institutional review board. Cardiomyopathy patients were retrospectively identified who had undergone endomyocardial biopsy and cardiac MR at one institution during a 5-year period. Forty-seven patients (53% male; mean age, 46.8 years) had undergone diagnostic cardiac MR and endomyocardial biopsy. Thirteen healthy volunteers (54% male; mean age, 38.1 years) underwent cardiac MR as a reference. Myocardial T1 mapping was performed 10.7 minutes 6 2.7 (standard deviation) after bolus injection of 0.2 mmol/kg gadolinium chelate by using an inversion-recovery Look-Locker sequence on a 1.5-T MR imager. Late gadolinium enhancement was assessed by using gradientecho inversion-recovery sequences. Cardiac MR results were the consensus of two radiologists who were blinded to histopathologic findings. Endomyocardial biopsy fibrosis was quantitatively measured by using automated image analysis software with digital images of specimens stained with Masson trichrome. Histopathologic findings were reported by two pathologists blinded to cardiac MR findings. Statistical analyses included Mann-Whitney U test, analysis of variance, and linear regression. Results:Median myocardial fibrosis was 8.5% (interquartile range, 5.7-14.4). T1 times were greater in control subjects than in patients without and in patients with evident late gadolinium enhancement (466 msec 6 14, 406 msec 6 59, and 303 msec 6 53, respectively; P , .001). T1 time and histologic fibrosis were inversely correlated (r = 20.57; 95% confidence interval: 20.74, 20.34; P , .0001). The area under the curve for myocardial T1 time to detect fibrosis of greater than 5% was 0.84 at a cutoff of 383 msec. Conclusion:Cardiac MR with T1 mapping can provide noninvasive evidence of diffuse myocardial fibrosis in patients referred for evaluation of cardiomyopathy.q RSNA, 2012

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A comprehensive histopathological evaluation of vascular medial fibrosis: Insights into the pathophysiology of arterial stiffening

Cited by 58 publications

References 27 publications

Myoarchitectural and functional alterations in rabbit external anal sphincter muscle following experimental surgical trauma

Myoarchitectural and functional alterations in rabbit external anal sphincter muscle following experimental surgical trauma

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

T1 Mapping in Cardiomyopathy at Cardiac MR: Comparison with Endomyocardial Biopsy

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