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Biomedical subjects

Renu Virmani

Publications and source records attributed to Renu Virmani.

At least 55 records · Page 3Linked to original sources
PubMed2005

Miniature self-contained intravascular magnetic resonance (IVMI) probe for clinical applications.

A miniature (1.73 mm in diameter) NMR probe, which contains a magnet and a radiofrequency (RF) coil, is presented. This probe is integrated at the tip of a standard catheter and can be inserted into the human coronary arteries, creating local magnetic fields needed to obtain the NMR signal from the blood vessel walls, without the need for external magnet or RF coils. The basic theory governing the probe performance in terms of signal-to-noise-ratio and contrast parameters is presented, along with measured results from test samples. The NMR signal can be analyzed to obtain tissue contrast parameters such as T1, T2 and the diffusion coefficient, which may be used to detect lipid-rich vulnerable plaques in the coronary arteries.

Blood Vessel Prosthesis↗
PubMed2005

Left ventricular noncompaction: a pathological study of 14 cases.

Left ventricular noncompaction (LVNC) has been recently proposed as a specific form of cardiomyopathy. There have been few pathological series describing gross and microscopic findings of this entity, especially in children. We present findings of 14 hearts (13 autopsy and 1 explant) with LVNC (isolated and associated with congenital heart disease), defined by poorly developed left ventricular (LV) papillary muscles and a noncompact inner LV myocardial layer comprising more than 50% of the LV thickness. The mean age at death/explant was 3.6 years (median, 2.5 months); there were 6 boys and 8 girls. The symptoms were sudden unexpected death (10) and heart failure (4). The diagnosis was suspected before death in only 1 of 13 autopsy cases. Right ventricular involvement (> 75% ventricular thickness comprised of noncompacted area with recess adjacent to tricuspid valve) was seen in 6 of 14 hearts. One patient had a sibling with pulmonary stenosis, but there was no other known familial cardiomyopathy. Endocardial fibroelastosis was a characteristic histological feature, as well as anastomosing or polypoid endocardial trabeculations, which resulted in staghorn-shaped, endocardial-lined recesses. There was a high rate of other cardiac anomalies, which often coexisted and were not clearly related to the LVNC, present in 8 cases (nonisolated LVNC): ventricular septal defect (4/14), anomalous venous pulmonary veins (1/14), coronary ostial stenosis (1/14), histiocytoid cardiomyopathy (1/14), polyvalvar dysplasia (2/14), and pulmonary stenosis (2/14). In the 6 isolated LVNC, there were 2 malformed atrioventricular valves (1 mitral and 1 tricuspid), which appeared part of the ventricular maldevelopment. There were no differences in histological or gross patterns of the noncompacted regions between the isolated and nonisolated LVNC. LVNC is frequently associated with other cardiac defects, especially when causing sudden death in infants and children. A clear-cut morphological distinction between "isolated" and "secondary" LVNC was not apparent. The pathologist should be aware of the entity because the diagnosis is often first established at autopsy.

Autopsy↗
PubMed2005

Microvessels in chronic total occlusions: pathways for successful guidewire crossing?

Arterial chronic total occlusions (CTO) are a common and clinically relevant problem in patients with coronary artery disease. Percutaneous coronary intervention (PCI) success rates in a wide range of CTO are low, primarily due to inability of guidewire crossing. The pathophysiology of CTO is poorly understood and limits our ability to introduce innovative therapies. Recent studies from our laboratory have suggested that microvessel formation within arterial CTO is a complex process with temporal and regional differences. Moreover, there is evidence from pilot studies that the presence of either microvessels or the particular extracellular matrix environment in the adjacent perivascular tissue can facilitate guidewire crossing and successful PCI. Currently, studies are underway in our experimental CTO model to delineate the pathophysiology of microvessel formation in CTO and its potential role in PCI.

Animals↗
PubMed2005

Evaluation of a novel endoluminal vascular occlusion device in a porcine model: early and late follow-up.

PURPOSE: To evaluate the efficacy of a new vascular occlusion device (VOD) in a preclinical controlled study versus embolization coils. METHODS: The Biomerix VOD was made from a biodurable porous polyurethane matrix in the shape of a cylinder measuring 1.5 cm long by 6.0 mm wide. Thirty-three swine were selected to undergo embolization of a 3 to 5-mm-diameter iliac artery using either a single VOD (27 animals) or sufficient Cook fibered stainless steel coils to achieve angiographic occlusion (6 controls). Test animals were assigned to undergo angiography at 1 week (n=11), 1 month (n=6), 3 months (n=6), or 6 months (n=4). Two control animals were assigned to angiographic follow-up at 1 week, 1 month, and 3 months. Test and control animals were euthanized at each time point to explant occluded vessels for histological analysis. Study endpoints were device utilization, time to occlusion, postdeployment migration, and persistent angiographic occlusion at 7, 30, 90, and 180 days. RESULTS: One VOD was deployed in each test animal, whereas a mean 3.3+/-0.8 coils were needed to achieve angiographic occlusion in the 6 controls (p<0.001). The time to occlusion was significantly shorter with the VOD (1.46+/-0.73 versus 5.83+/-1.60 minutes for the coils; p<0.001). There was no evidence of recanalization or filling defects at the site of VOD deployment, while filling defects were seen in 3 of 6 coil-treated controls. The VOD arm showed superior angiographic occlusion versus coils at the 1-week, 1-month, and 3-month angiographic follow-up time points. Histological evaluation showed that the VOD was equivalent to the embolization coils at the 1-week (n=6) and 1-month (n=6) endpoint (100% luminal occlusion). In the 3-month group (n=6), the VOD showed 95% to 100% luminal occlusion versus 90% to 95% in the control animals. In the 6-month group, VOD showed 85% to 95% occlusion. CONCLUSIONS: The Biomerix VOD appears highly effective and reliable, resulting in significantly faster and longer lasting occlusion compared with fibered stainless steel embolization coils.

Angiography↗
PubMed2005

Resolution of apoptosis in atherosclerotic plaque by dietary modification and statin therapy.

UNLABELLED: Although apoptosis within atherosclerotic plaques is associated with plaque vulnerability and rupture, the role of inhibition of the apoptotic process is not clear. We evaluated the impact of dietary modification and statin therapy (measures known to favorably influence outcomes in coronary disease) on the incidence of apoptosis in experimental atherosclerotic lesions. METHODS: A total of 30 animals were studied; 1 group of 6 animals served as the controls (group 1), and the remaining 24 animals were subjected to balloon de-endothelialization of the abdominal aorta and a high-cholesterol diet. These atherosclerotic animals were randomized as follows: high-cholesterol diet for 4 mo (n=6; untreated atherosclerotic group [group 2]), high-cholesterol diet for 3 mo and normal chow diet for 1 mo (n=6; diet withdrawal group [group 3]), and high-cholesterol diet for 4 mo and simvastatin orally every day of the last month (n=6; statin therapy group [group 4]). 99mTc-Annexin A5 was used for noninvasive detection of apoptosis in groups 1-4. The remaining 6 rabbits on a high-cholesterol diet for 4 mo were studied with radiolabeled mutant annexin A5 (n=6; nonspecific control group [group 5]). Quantitative annexin A5 uptake in the abdominal aorta was determined and compared with the histologic and immunohistochemical characteristics of the atherosclerotic lesions. RESULTS: Maximum annexin A5 uptake (mean+/-SD, 0.051+/-0.009 percentage injected dose per gram [%ID/g] of tissue) was observed in the untreated atherosclerotic animals. The uptake was substantially reduced in the diet withdrawal (0.03+/-0.006%ID/g; P<0.0001) and statin therapy (0.03+/-0.006%ID/g; P<0.0001) groups. The plaques in the untreated high-cholesterol group demonstrated advanced atherosclerotic lesions. On the other hand, the diet withdrawal and statin therapy groups showed histologic characteristics of stabilization, including the resolution of macrophage infiltration and an increase in smooth muscle cell content. There was a marked reduction in the apoptosis of macrophages. No significant uptake of annexin A5 or mutant annexin A5 was seen in rabbits on the normal chow diet or atherosclerotic rabbits, respectively. CONCLUSION: Dietary modification and statin therapy in atherosclerosis lead to a reduction in apoptosis and contribute to plaque stabilization. It can be hypothesized that a reduction in apoptosis is a favorable process in atherosclerotic disease.

Animal Feed↗
PubMed2004

Sudden death in young adults: a 25-year review of autopsies in military recruits.

BACKGROUND: Sudden death among military recruits is a rare but devastating occurrence. Because extensive medical data are available on this cross-sectional and diverse population, identification of the underlying causes of sudden death may promote health care policy to reduce the incidence of sudden death. OBJECTIVE: To determine the causes of nontraumatic sudden death among a cohort of military recruits. DESIGN: Retrospective cohort study using demographic and autopsy data from the Department of Defense Recruit Mortality Registry. SETTING: Basic military training. PATIENTS: All nontraumatic sudden deaths from a monitored 6.3 million men and women age 18 to 35 years. MEASUREMENTS: Descriptive analysis, crude mortality rates of causes of sudden death, and frequency of events as a function of cause of death. RESULTS: Of 126 nontraumatic sudden deaths (rate, 13.0/100,000 recruit-years), 108 (86%) were related to exercise. The most common cause of sudden death was an identifiable cardiac abnormality (64 of 126 recruits [51%]); however, a substantial number of deaths remained unexplained (44 of 126 recruits [35%]). The predominant structural cardiac abnormalities were coronary artery abnormalities (39 of 64 recruits [61%]), myocarditis (13 of 64 recruits [20%]), and hypertrophic cardiomyopathy (8 of 64 recruits [13%]). An anomalous coronary artery accounted for one third (21 of 64 recruits) of the cases in this cohort, and, in each, the left coronary artery arose from the right (anterior) sinus of Valsalva, coursing between the pulmonary artery and aorta. LIMITATIONS: This cohort underwent a preenlistment screening program that included history and physical examination; this may have altered outcomes. CONCLUSIONS: Cardiac abnormalities are the leading identifiable cause of sudden death among military recruits; however, more than one third of sudden deaths remain unexplained after detailed medical investigation.

Adolescent↗
PubMed2004

Decorin promotes aortic smooth muscle cell calcification and colocalizes to calcified regions in human atherosclerotic lesions.

OBJECTIVE: Ectopic calcification localized to the intima of atherosclerotic plaque is a risk marker for cardiovascular events and increases the risk of aortic dissection during angioplasty. A variety of extracellular matrix molecules such as collagen type 1, bone sialoprotein, and osteopontin are known to regulate the biomineralization of bone and ectopic vascular calcification. In the present study, it was investigated whether decorin, a small leucine-rich proteoglycan expressed in bone and atherosclerotic plaque, is involved in arterial calcification. METHODS AND RESULTS: Calcification was induced in cultured bovine aortic smooth muscle cell (BASMC) by the addition of beta-glycerophosphate or inorganic phosphate. Northern and Western analysis revealed that decorin expression was strongly upregulated in mineralizing BASMC. Furthermore, overexpression of decorin using a retroviral expression vector resulted in a 3- to 4-fold elevation of calcium deposited on the BASMC monolayer. Increased calcification in response to decorin could also be mimicked by adding exogenous decorin to the cultures. In addition, human coronary atherosclerotic lesions taken from sudden-death patients showed marked colocalization of calcium deposits with decorin. CONCLUSIONS: Decorin induces calcification of arterial smooth muscle cell cultures and colocalizes to mineral deposition in human atherosclerotic plaque, suggesting that decorin functions as promoter of intimal calcification.

Animals↗
PubMed2004

Actinomycin-eluting stent for coronary revascularization: a randomized feasibility and safety study: the ACTION trial.

OBJECTIVES: We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novo native coronary lesions. BACKGROUND: Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation. METHODS: The multi-center, single-blind, three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30 days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory. RESULTS: The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction. CONCLUSIONS: The results of the ACTION trial indicate that all anti-proliferative drugs will not uniformly show a drug class effect in the prevention of restenosis.

Aged↗
PubMed2004

Preclinical restenosis models and drug-eluting stents: still important, still much to learn.

Percutaneous coronary intervention continues to revolutionize the treatment of coronary atherosclerosis. Restenosis remains a significant problem but may at last be yielding to technologic advances. The examination of neointimal hyperplasia in injured animal artery models has helped in our understanding of angioplasty and stenting mechanisms, and as drug-eluting stent (DES) technologies have arrived, they too have been advanced through the study of animal models. These models are useful for predicting adverse clinical outcomes in patients with DESs because suboptimal animal model studies typically lead to problematic human trials. Similarly, stent thrombosis in animal models suggests stent thrombogenicity in human patients. Equivocal animal model results at six or nine months occasionally have been mirrored by excellent clinical outcomes in patients. The causes of such disparities are unclear but may result from differing methods, including less injury severity than originally described in the models. Ongoing research into animal models will reconcile apparent differences with clinical trials and advance our understanding of how to apply animal models to clinical stenting in the era of DESs.

Animals↗
PubMed2004

Extracellular matrix changes in stented human coronary arteries.

BACKGROUND: Restenosis after stenting occurs secondary to the accumulation of smooth muscle cells (SMCs) and extracellular matrix (ECM), with the ECM accounting for >50% of the neointimal volume. The composition of the in-stent ECM has not been well characterized in humans. METHODS AND RESULTS: Postmortem human coronary arteries (n=45) containing stents underwent histological assessment of neointimal proteoglycans, hyaluronan, collagen (types I and III), SMCs, and CD44 (a cell surface receptor for hyaluronan). The mean duration of stent implantation was 18.7 months; stents in place > or =3 to <9 months (n=17) were assigned to group 1, stents > or =9 to <18 months old (n=19) to group 2, and stents > or =18 months old (n=9) to group 3. In groups 1 and 2, neointimal versican and hyaluronan staining was strongly positive, colocalized with alpha-actin-positive SMCs, and was greater in intensity compared with group 3. Conversely, decorin staining was greatest in group 3. The neointima of both group 1 and 2 stents was rich in type III collagen, with reduced staining in group 3. Type I collagen staining was weakest in group 1 stents, with progressively stronger staining in groups 2 and 3. SMC density and stent stenosis were significantly reduced in group 3 stents compared with groups 1 and 2. CD44 staining colocalized with macrophages and was associated with increased neointimal thickness. CONCLUSIONS: The ECM within human coronary stents resembles a wound that is not fully healed until 18 months after deployment, followed by neointimal retraction. ECM contraction may be a target for therapies aimed at stent restenosis prevention.

Aged↗
PubMed2004

Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study.

OBJECTIVE: Coronary atherosclerotic plaque composition of diabetic subjects and localization of receptor for advanced glycation end products (RAGE) and its ligands have not been extensively studied. METHODS AND RESULTS: Hearts from diabetic subjects and age, race, and sex-matched nondiabetic subjects dying suddenly were examined. Coronary arteries were dissected and lesions were evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death (apoptosis) were also determined. Lesions from type II diabetic subjects had larger mean necrotic cores (P=0.01) and greater total and distal plaque load (P<0.001) than nondiabetic subjects. Necrotic core size correlated positively with diabetic status, independent of other risk factors. Intimal staining for macrophages, T-cells, and HLA-DR was also significantly greater in diabetic subjects (P=0.03, P=0.003, and P<0.0001), respectively. The association of increased macrophage infiltrate was independent of cholesterol levels and patient age. Expression of RAGE and EN-RAGE was significantly greater in diabetic subjects (P=0.004) and was associated with apoptotic smooth muscle cells and macrophages. CONCLUSIONS: In sudden coronary death, inflammation and necrotic core size play a greater role in the progression of atherosclerosis in diabetic subjects. The expression of RAGE and EN-RAGE may further compromise cell survival and promote plaque destabilization.

Adult↗
PubMed2004

Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious?

BACKGROUND: The US Food and Drug Administration recently issued a warning of subacute thrombosis and hypersensitivity reactions to sirolimus-eluting stents (Cypher). The cause and incidence of these events have not been determined. METHODS AND RESULTS: We present findings of a 58-year-old man who died of late stent thrombosis 18 months after receiving 2 Cypher stents for unstable angina. Although angiographic and intravascular ultrasound results at 8 months demonstrated the absence of neointimal formation, vessel enlargement was present. An autopsy showed aneurysmal dilation of the stented arterial segments with a severe localized hypersensitivity reaction consisting predominantly of T lymphocytes and eosinophils. CONCLUSIONS: The known pharmacokinetic elution profile of Cypher stents and the presence of polymer fragments surrounded by giant cells and eosinophils suggest that a reaction to the polymer may have caused late stent thrombosis. Careful long-term follow-up of patients with vessel enlargement after Cypher stent placement is recommended.

Angina, Unstable↗
PubMed2004

Short-term intravenous eptifibatide infusion combined with reduced dose recombinant tissue plasminogen activator inhibits platelet recruitment at sites of coronary artery injury.

OBJECTIVES: This study was designed to determine in a dog model of coronary thrombosis whether short-term eptifibatide (Ep) combined with low-dose plasminogen activator (rt-PA) inhibits platelet recruitment at sites of endothelial damage after normalization of platelet function. BACKGROUND: Ep plus reduced-dose rt-PA has not previously been shown to render a recanalized coronary artery resistant to platelet recruitment after normalization of platelet function. METHOD: Inhibition of platelet recruitment was studied by scanning electron microscopy (SEM) in a canine model of left anterior descending (LAD) thrombosis. In phase I treatment groups were: 1) Ep (n = 6); 2) Ep + rt-PA (n = 6); 3) rt-PA (n = 6); and 4) placebo (n = 4). Coronary blood flow was monitored and LAD segments excised for SEM after 90-min infusion of study drug. In phase II, dogs were randomized to Ep alone (n = 5) or to Ep + rt-PA (n = 5). Coronary blood flow was monitored during and 120 min after cessation of drug when platelet function had returned to normal and LAD segments were excised. RESULTS: All animals except placebo showed reflow. In phase I, SEM showed an absence of platelet aggregates with Ep alone and with Ep + rt-PA, but not with rt-PA alone. In phase II, SEM showed an intimal surface devoid of mural thrombus and platelet aggregates only in Ep + rt-PA treated arteries. Ep-alone treated arteries showed new platelet aggregates at sites of residual mural thrombus. CONCLUSIONS: Short-term infusion Ep plus low-dose rt-PA acutely neutralizes the ability of damaged endothelial surfaces to recruit new platelets by inhibiting platelet aggregation and eliminating residual mural thrombus.

Animals↗
PubMed2004

Initial experience with the novel 6 Fr-compatible system for debulking de novo coronary arterial lesions.

The purpose of this study was to determine the efficacy of a novel system for debulking of de novo native coronary arterial lesions. The Helixciser De Novo system is a novel 6 Fr-compatible catheter with a cutter encased in a slotted-orifice housing to excise atheromatous plaque. The cutter rotates at 15,000 rpm, debulking the plaque as it tracks through the lesion over a straight wire or a self-expanding nitinol helical-shaped wire. The tissue is aspirated via an Archimedes screw pump to vacuum collection chamber. The device was evaluated in a porcine toxic coronary stent model of chronic occlusion and in five patients with focal de novo native coronary arterial lesions. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) and volumetric intravascular ultrasound (IVUS) analysis were performed. In a porcine model of chronic occlusion, QCA demonstrated pretreatment minimal lumen diameter (MLD) increased from 0.77 +/- 0.59 to 1.88 +/- 0.25 mm postdebulking. IVUS analysis demonstrated pretreatment lumen volume (LV) increased from 15.8 +/- 22.2 to 46.4 +/- 28.9 mm(3) postdebulking. In human clinical feasibility cases, QCA demonstrated pretreatment MLD increased from 0.96 +/- 0.40 to 2.04 +/- 0.19 mm postdebulking. IVUS analysis demonstrated pretreatment LV increased from 38.40 +/- 12.78 to 52.05 +/- 15.68 mm(3) postdebulking. Preliminary results document the feasibility of Helixcision De Novo for treatment of focal de novo native coronary arterial lesions. Quantitative angiographic and IVUS analysis indicate that this system can effectively debulk plaque from selected noncalcified atherosclerotic lesions and thus may represent an alternative treatment strategy for coronary artery disease.

Animals↗
PubMed2004

Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece.

A group of investigators met for two days in Santorini, Greece, to discuss progress in the field of identification and treatment of high risk/vulnerable atherosclerotic plaques and patients. Many differences in the manner in which terms are being utilized were noted. It was recognized that increased understanding of the pathophysiology of coronary thrombosis and onset of acute coronary syndromes has created the need for agreement on nomenclature. The participants spent considerable time discussing the topic and reached agreement on their own usage of the terms as described below. It is the hope that this usage might be of value to the larger community of scientists working in this field, and that widespread adoption of a common nomenclature would accelerate progress in the prevention of acute coronary events.

Calcinosis↗