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Biomedical subjects

J Butany

Publications and source records attributed to J Butany.

At least 37 records · Page 2Linked to original sources

Velocity and wall shear stress patterns in the human right coronary artery.

Blood flow dynamics in the human right coronary artery have not been adequately quantified despite the clinical significance of coronary atherosclerosis. In this study, a technique was developed to construct a rigid flow model from a cast of a human right coronary artery. A laser photochromic method was used to characterize the velocity and wall shear stress patterns. The flow conditions include steady flow at Reynolds numbers of 500 and 1000 as well as unsteady flow with Womersley parameter and peak Reynolds number of 1.82 and 750, respectively. Characterization of the three-dimensional geometry of the artery revealed that the largest spatial variation in curvature occurred within the almost branch-free proximal region, with the greatest curvature existing along the acute margin of the heart. In the proximal segment, high shear stresses were observed on the outer wall and lower, but not negative, stresses along the inner wall. Low shear stress on the inner wall may be related to the preferential localization of atherosclerosis in the proximal segment of the right coronary artery. However, it is possible that the large difference between the outer and inner wall shear stresses may also be involved.

Blood Flow Velocity↗

Morphologic findings in explanted Hancock II porcine bioprostheses.

BACKGROUND AND AIM OF THE STUDY: Heart valve substitutes have been in use for over 30 years. Bioprosthetic heart valves have many advantages, but unfortunately suffer tissue degeneration and calcification. Many approaches, such as antimineralization treatment to prevent or delay these changes, have been tried. We present the morphologic findings from a series of Hancock II (antimineralization-treated) porcine bioprostheses. METHODS: Forty-five Hancock II porcine valve bioprostheses (16 mitral, 29 aortic) surgically explanted between March 1991 and December 1995 at the Toronto Hospital were analyzed for morphologic findings and causes of failure. The prostheses were implanted in 36 adults (mean age 55+/-14.7 years, range: 27 to 75 years) and had been in place between one month and 11 years (mean 5.1+/-3.3 years). RESULTS: Structural valve deterioration (SVD) characterized by tissue degeneration, calcification, cusp tears and increased stiffness, was the single most significant finding and cause of failure, affecting 56% of valves. Some degree of calcification was seen in 55% of prostheses, with severe calcification (grade 3 or 4) in 18%. Aortic bioprostheses showed more severe and earlier calcification than mitral ones (p = 0.03). Compared with the standard Hancock valve, the low incidence of significant calcification suggests a beneficial protective effect of antimineralization treatment. Severe pannus (grade 3 or 4) was seen in 60% of these prostheses. The pattern of pannus growth differs between mitral and aortic sites; mitral prostheses showed pannus on the flow and non-flow surfaces, often associated with cusp tears, mitral regurgitation and mitral leaflet preservation. A similar degree of pannus on aortic prostheses was invariably present on the flow surface and extended onto the valve cusps, leading to changes in the orifice which may cause clinical aortic stenosis. Infective endocarditis was seen in 15 prostheses (five mitral, 10 aortic) from 11 patients, and comprised the second most important cause of prosthesis failure. The risk of recurrent endocarditis was particularly high in patients who had infective endocarditis before valve replacement, even at five and six years post implantation. CONCLUSIONS: SVD is the major finding in explanted Hancock II bioprostheses and is associated with cusp tears and calcification. The incidence of tissue calcification appears lower at the mitral site. These findings suggest that the antimineralization treatment had some beneficial effect. Pannus associated with prosthesis dysfunction at the mitral sites is a prominent finding and on the non-flow surface may be related to the native mitral valve-conserving procedure.

Adult↗

Effect of a single bolus of intracoronary basic fibroblast growth factor on perfusion in an ischemic porcine model.

Basic fibroblast growth factor (bFGF) has been shown to induce angiogenesis in various animal models, but the methods of administration used experimentally are not clinically feasible. The objective of this study was to determine whether a single intracoronary bolus injection of bFGF would improve coronary perfusion in a porcine ischemic model that mimics clinical chronic ischemia. A copper coil studded with gold was delivered into the proximal right coronary artery of juvenile Yorkshire pigs and deployed by interventional techniques. After a four-week interval for stenosis maturation, bFGF (100 micrograms) was administered by bolus injection into the left coronary artery in five animals, and vehicle alone was administered in four animals. Angiogenesis and change in right coronary perfusion area were assessed two weeks later by angiography, myocardial contrast echocardiography and immunohistochemistry. The right coronary perfusion area increased significantly after treatment in all but one of the animals that received bFGF but not in any of the controls. Intimal hyperplasia was not induced by bFGF. Capillary density determined histochemically was not different in the two groups. In conclusion, in a porcine ischemic model, bFGF administered by a single bolus intracoronary injection into the contralateral artery improved antegrade perfusion into the ischemic territory although without histological evidence of angiogenesis. This preliminary work merits further investigation.

Animals↗

Left ventricular involvement in right ventricular dysplasia/cardiomyopathy.

OBJECTIVE: To characterize pathological features of left ventricular (LV) involvement in right ventricular dysplasia/cardiomyopathy (RVD/C). DESIGN: Retrospective morphological case study. SETTING: Two referral-based university medical centres. MATERIALS: Seventeen hearts were studied: 15 from sudden cardiac deaths outside hospital and two explanted hearts, one removed for intractable arrhythmias and the other for right-sided heart failure. The subjects (three female) were aged 16 to 60 years. MAIN RESULTS: All had typical right ventricular features of RVD/C and morphological evidence of LV wall involvement, seven with microscopic changes only. Of 10 hearts with gross and microscopic lesions, nine had large or laminar segments involved. The LV free wall was affected in all cases and the ventricular septum (VS) in 15. Sixteen hearts were hypertrophied. In involved areas, the LV or VS walls were of 'normal' thickness or slightly thinned. Five histological patterns of involvement were recognized, of which four were found in the LV. More severe LV involvement was seen in the hearts of older patients. Complete transmural fatty replacement of the myocardium was not observed, nor were the LVs aneurysmal. Minimal or mild focal aggregates of inflammatory cells were seen in nine hearts and moderate inflammatory changes in two. Inflammation was usually associated with myocyte atrophy and only rarely with myonecrosis. CONCLUSIONS: This study suggests that patients with RVD/C who live long enough will likely have LV free wall involvement with frequent VS involvement. Pathologists may miss LV involvement on gross examination. It should be sought diligently in patients dying of the condition or receiving transplants for heart failure. Appropriate histological sections from both free wall and septum must be examined.

Adolescent↗

Primary pericardial mesothelioma presenting as constrictive pericarditis.

Primary pericardial mesothelioma is a rare tumour, often discovered late in a patient's clinical course or at autopsy. Antemortem diagnosis is usually made at the time of surgery. A patient who presented with what appeared to be viral pericarditis in October 1997 is reported. Recurrent symptoms prompted re-evaluation with echocardiography, chest computed tomography, magnetic resonance imaging, cardiac catheterization and a diagnosis of constrictive pericarditis. Associated hepatic dysfunction was found to be secondary to congestion. After operative pericardiotomy and histological examination, primary pericardial mesothelioma was diagnosed. The lesion was surgically debulked.

Diagnosis, Differential↗

The Toronto SPV bioprosthesis: review of morphological findings in eight valves.

The morphological findings in eight explanted Toronto SPV bioprostheses were described. Clinical records were reviewed for patient information and data regarding the explanted bioprosthesis, all of which were analyzed in detail by gross and histological examination. All valves were also examined radiologically and detailed specimen photographs obtained. When warranted, tissue cultures were taken and special stains for microorganisms obtained. The Toronto SPV bioprosthesis has been used for aortic valve replacement in 270 patients since its introduction in 1991. The follow-up evaluation was 99.5% complete. Eight valves have been explanted: three at surgery and five at autopsy. Patient age ranged from 35 to 69 years, with five male and three female patients. Indications for aortic valve replacement were aortic stenosis in all cases. Implant duration ranged from 5 weeks to just over 6 years (mean 38 months). Early failures (2) were due to infective endocarditis. Two patients died of acute myocardial infarction, related to pre-existing coronary artery disease, and two died from lung cancer. All late explants showed host tissue growth (grade 2-3), with variable extension onto both the proximal and distal suture lines, as well as extension onto the cusps and commissures on the flow and nonflow surfaces. Extension of pannus onto native aortic tissues was seen but did not encroach on the coronary ostia. Tissue degenerative changes were present, as were small tears (type 1) in two valves. Mild calcification was seen in two valves. The Toronto SPV has excellent clinical performance at up to 8 years of follow-up evaluation. In this series, early failures are related to infective endocarditis, and later explants (6 of 8) are associated with mild tissue degeneration and an occasional cusp tear. At up to 5 years, only minimal/mild calcification was seen in two of the eight valves.

Adult↗

Autopsies in acute type A aortic dissection. Surgical implications.

BACKGROUND: This study was undertaken to review autopsy findings in operative and nonoperative settings to define anatomic pathology, cause of death, and theoretical implications of operative and perfusion management strategies for acute Stanford type A dissection. METHODS AND RESULTS: Fifty autopsies for acute type A dissection performed between 1977 and 1995 were reviewed. Twenty-nine patients had no operative therapy (group A). Twenty-one patients received an operation (group B). Cause of death in the nonoperated group was tamponade or rupture in 23 patients (23 of 29, 79%). In the operated group, 1 patient died of rupture (1 of 21, 5%). The 2 most common causes of death in the operated group were major brain injury (7 of 21, 33%) and cardiac failure (7 of 21, 33%). Intimal disruption was present in 92% of patients (45 of 49). Twenty-four percent of these (12 of 49) had a secondary intimal injury site. Theoretic femoral arterial perfusion and application of an ascending aortic cross clamp would have left 42% of patients (21 of 50) at risk of false lumen perfusion against the aortic cross clamp. Replacement of the ascending aorta alone would have left residual arch intimal disruption in 32% of patients (16 of 50). Open arch inspection and repair when appropriate would have left a minimum number of patients with distal intimal disruption (8 of 50, 16%). CONCLUSIONS: Operative therapy successfully manages the primary cause of death in acute type A dissection. A theoretical repair that uses the open arch technique followed by antegrade perfusion eliminates or minimizes the risk of false lumen perfusion in the greatest number of patients. This technique may diminish neurological injury and distal anastomosis bleeding, thereby improving outcomes.

Acute Disease↗

Compliance mismatch may promote graft-artery intimal hyperplasia by altering suture-line stresses.

The role of graft-artery compliance mismatch in the development of distal anastomotic intimal hyperplasia (DAIH) is not yet resolved. Although DAIH develops at all surgically created anastomoses, increased compliance mismatch does not lead to greater hyperplasia formation in end-to-end anastomoses, but in end-to-side anastomoses, it leads to a profound increase in hyperplasia. The current study was undertaken to determine whether suture-induced anastomotic stresses could explain these findings. A large strain finite element analysis of vascular wall mechanics was performed to compare the influence of compliance mismatch on intramural stresses in end-to-end versus end-to-side anastomoses. A novel modelling approach was implemented which includes suture-induced stress concentrations. End-to-end and end-to-side graft-artery simulations were executed using (1) artery (compliance = C = 0.44% kPa(-1)), (2) vein (C = 0.33% kPa(-1)), and (3) Dacron (C = 0.14% kPa(-1)) grafts. Residual stresses due to axial tension were included and the anastomoses were statically inflated to 13.3 kPa (100 mmHg). Elevated intramural stresses were found to exist at both the end-to-end and end-to-side graft-artery junctions; however, in the end-to-end anastomosis, the maximum anastomotic stress was not a function of the graft compliance, whereas in the end-to-side anastomosis, the maximum stress was a strong function of graft compliance. For the 45 degree end-to-side geometry considered in this study, the maximum anastomotic stress concentration obtained using a stiff Dacron graft was more than 40% greater than that obtained using a compliant artery graft. In the end-to-end anastomosis, the Dacron graft led to a less than 5% increase in maximum stress over the artery graft. Therefore, increased compliance mismatch increases stresses and promotes DAIH in end-to-side junctions, but, it has little influence on either stresses or DAIH in end-to-end junctions. Thus, the proliferative influence of increased compliance mismatch on suture-line hyperplasia in end-to-side anastomoses can be explained by the resulting increase in intramural stresses. In addition, since high stresses were found in both geometries, elevated suture-line intramural stresses may be an important proliferative stimulus for intimal hyperplasia formation in all vascular reconstructions.

Arteries↗

Cardiac transplantation for Fabry's disease.

Fabry's disease is a rare cause of cardiomyopathy. There are no previous reported cases of cardiac transplantation for end-stage cardiomyopathy secondary to Fabry's disease. Recurrence of disease in allografts following renal transplantation has been documented, but the course following heart transplantation is not known. A 53-year-old female presented with congestive heart failure and was found to have end-stage restrictive cardiomyopathy secondary to Fabry's disease, as diagnosed by endomyocardial biopsy. She underwent cardiac transplantation. Eight weeks post-transplantation, electron microscopy of an endomyocardial biopsy specimen showed concentric lamellar inclusions within myocytes similar to inclusions seen in the preoperative biopsy and the explanted heart. However, subsequent biopsies up to one year after heart transplantation did not show any such inclusions. There has been no clinical evidence of Fabry's cardiomyopathy. Heart transplantation is a viable option for end-stage Fabry's cardiomyopathy. However, long term follow-up is required to determine clinical outcome.

Fabry Disease↗

Antiphospholipid antibody syndrome with involvement of a bioprosthetic heart valve.

The antiphospholipid antibody syndrome (APS) is defined broadly by the presence of antiphospholipid antibodies, venous and arterial thrombosis, thrombocytopenia and fetal wastage. APS can be primary or secondary, in which APS occurs in the context of another defined disease such as autoimmune disease, malignancy, drug-induced disease, etc. APS is primary in one-half of patients and secondary in the rest, mainly to systemic lupus erythematosus. Several cardiac manifestations of APS have been reported. These include valvular heart disease, coronary artery disease, intracardiac thrombosis and cardiomyopathy. The literature has shown a prevalence of approximately 35% of valvular abnormalities detected by echocardiography in patients with APS. A patient with primary APS who developed aortic stenosis with vegetations on a bioprosthetic porcine valve is presented.

Adult↗

Cardiac metastasis from primary cervical squamous cell carcinoma: three case reports and a review of the literature.

Clinically evident cardiac metastases from malignant neoplasms are uncommon, occurring most commonly in association with lung and breast carcinoma, lymphoma, leukemia and melanoma. The vast majority, over 90%, present with pericardial involvement. Squamous cell carcinomas of the cervix rarely produce cardiac metastases, with endomyocardia metastases being particularly rare. Three patients are reported who presented with primary squamous cell carcinoma of the cervix and developed this pattern of metastasis, one of whom was diagnosed at endomyocardial biopsy and the other two at autopsy. The paucity of such cases in the literature emphasizes the uniqueness of this phenomenon.

Adult↗

Incidental detection of an aortic valve papillary fibroelastoma by echocardiography in an asymptomatic patient presenting with hypertension.

Papillary fibroelastomas are rare, frond-like tumours of uncertain etiology seen on cardiac valves, uncommonly found antemortem. They carry a significant risk of embolization, making their detection and excision during life an important issue. A case of an aortic valve papillary fibroelastoma is described, which was found at echocardiography in a patient being assessed for previously unrecognized, severe hypertension.

Aortic Valve↗

Quantification of cardiac and tissue iron by nuclear magnetic resonance relaxometry in a novel murine thalassemia-cardiac iron overload model.

OBJECTIVE: To determine whether nuclear magnetic resonance (NMR) relaxation parameters can be used to quantify iron in tissues, the relationship between NMR spectrometric T2 relaxation measurements and tissue iron concentration were verified in a novel murine cardiac iron overload model. METHODS: Congenital heterozygous thalassemic mice and controls were injected with intraperitoneal iron or saline and were sacrificed at three weeks. Samples of liver, heart and peripheral muscle were subjected to NMR relaxation measurements and continuous distribution analysis. Tissue ferritin levels were determined with immunoadsorbance techniques, and elemental iron was assayed by flame atomic absorption. Tissues were analyzed pathologically with hematoxylin and eosin and Prussian blue staining to confirm the localization of iron. RESULTS: This murine iron loading model was uniquely successful in loading iron into the major organs, especially the heart, and produced significant reductions in T1 and T2 NMR relaxation values. There was a good correlation between soluble ferritin and total iron levels (r=0.92), indicating that there is a constant and significant fraction of total iron present in ferritin irrespective of absolute iron concentrations. Regression analysis between total iron content and T2 relaxivity showed a linear relationship (r=0.96), suggesting that the T2 relaxation parameter is related to tissue iron concentration. The regression relationship suggested that NMR can detect iron levels as low as 0.1 mg/g of tissue. CONCLUSIONS: Parenteral iron loading in mice produces unique iron overload in major organs, including the heart. Local iron deposition is detectable by NMR relaxometry at 0.1 mg/g or higher. There is a linear relationship between iron concentration and T2 relaxivity. Thus, NMR may be an important and useful clinical tool to quantify iron excess in various pathobiological states of human disease due to iron overload, including heart disease.

Animals↗

Abnormalities in intramyocardial arteries detected in cardiac transplant biopsy specimens and lack of correlation with abnormal intracoronary ultrasound or endothelial dysfunction in large epicardial coronary arteries.

OBJECTIVES: We sought to determine whether abnormalities in small intramyocardial vessels could be detected on routine cardiac transplant biopsy specimens and whether these features correlate with intimal thickening by intracoronary ultrasound and endothelial dysfunction in large epicardial vessels. BACKGROUND: Variability in clinical presentation of allograft vasculopathy suggests differential involvement of large and small vessels. Intracoronary ultrasound and endothelial function studies detect large-vessel abnormalities but may not reflect changes in small intramyocardial arteries. The latter could be detected in routine cardiac biopsy specimens by histologic and immunohistochemical studies. METHODS: Thirty-nine cardiac transplant recipients underwent intracoronary ultrasound and acetylcholine studies 5 to 7 days after endomyocardial biopsy. Biopsy tissue was evaluated for coronary artery endothelial plumping and intimal thickening and increased immunostaining for fibronectin, tumor necrosis factor-alpha and receptor for hyaluronan-mediated motility. Large-vessel disease was assessed by calculating an average intimal index from intracoronary ultrasound of the left anterior descending coronary artery. Endothelial function was determined by quantitative coronary analysis after acetylcholine challenge. RESULTS: Coronary arteries were found in the biopsy tissue of 30 (76%) of the 39 patients who formed the study group. Fourteen of 30 patients had abnormal histologic findings. Immunohistochemical analysis for fibronectin, possible in 20 of 30 patients, was positive in 14 (70%) of 20 and correlated with abnormal histologic findings (p = 0.01). Immunostaining was positive for tumor necrosis factor-alpha and receptor for hyaluronan-mediated motility in 12 (40%) and 13 (43%) of 30 patients, respectively. All patients had intimal thickening by intracoronary ultrasound, but intimal index did not correlate significantly with small-artery disease by histologic or immunohistochemical analysis. Large-vessel endothelial dysfunction in 13 patients (43%) did not correlate with either abnormal ultrasound findings or small-vessel disease. CONCLUSIONS: Intramyocardial arteries are readily observed in biopsy specimens from cardiac transplant recipients and provide useful information about allograft vasculopathy. Lack of correlation between intramyocardial and epicardial vessel disease suggests discordant progression of allograft vasculopathy.

Adult↗

Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis).

The pathogenesis of congestive cirrhosis is generally thought to be a reaction of the hepatic stroma to hypoxia, pressure, or necrosis. This does not explain the poor correlation between symptoms and severity of fibrosis and the irregular distribution of fibrosis within the liver. We have observed healed hepatic vein (HV) thrombosis in patients with congestive heart failure (CHF). The purposes of this study were to document hepatic vascular lesions in autopsy livers of patients with chronic CHF, to determine the role of these lesions in the pathogenesis of congestive cirrhosis, and to refine the definition of congestive cirrhosis. Twenty-five livers were studied, 13 with multiple large blocks 4 x 5 cm. Sections were graded for parenchymal fibrous septa, sinusoidal fibrosis, and intimal fibrosis of portal veins (PVs) and HVs. Fibrous septa were found in livers of 7 of 13 patients with CHF and in none of 12 controls without CHF (P = .007). Parenchymal fibrosis was highly variable in distribution, often with severe septation in some areas and nearly normal morphology in others. Intimal fibrosis and obstruction of small- and medium-HVs were found only in livers of patients with CHF. The vascular lesions were confined to regions with fibrous septation and had morphology suggestive of organized thrombosis. Acute thrombi in sinusoids were noted in livers of 4 patients with CHF and in livers of 2 patients without CHF. These findings support the hypothesis that congestive cirrhosis is a response to intrahepatic thrombosis. The pattern of disease suggests that thrombus begins in sinusoids, occasionally propagates to HVs, and causes secondary local PV thrombosis, ischemia, parenchymal extinction, and fibrosis.

Aged↗

Are patients receiving amiodarone at increased risk for cardiac operations?

Amiodarone therapy has been implicated as a risk factor for cardiothoracic surgical procedures. In patients undergoing map-guided surgical procedures for the treatment of ventricular tachycardia, we compared the perioperative course of those receiving long-term amiodarone therapy (n = 36) versus that in those not receiving the drug (n = 31). The two groups were similar with respect to age, sex, presenting symptoms, functional class, extent of coronary artery disease, presence of a ventricular aneurysm, technique of ventricular tachycardia ablation, cross-clamp or pump time, the number of vessels grafted, the operative fluid balance, and a need for intraaortic balloon pump or inotropic agent support. In 5 patients receiving amiodarone, epinephrine was required to maintain a normal systemic vascular resistance and adequate arterial pressure. Postoperatively, 6 patients (17%) on amiodarone therapy suffered acute respiratory failure. In spite of aggressive therapy, 3 of these patients died. Only 1 patient not receiving amiodarone died of a stroke. We conclude that amiodarone therapy in patients undergoing open heart operations is associated with an increased risk of severe pulmonary complications (p = 0.03 by Fisher's exact test). Amiodarone therapy should be withheld in patients with ventricular tachycardia until they have been assessed as candidates for possible surgical intervention.

Aged↗