Biomedical subjects

Varun Kapila

Publications and source records attributed to Varun Kapila.

6 recordsLinked to original sources

PubMed2006

Natural history and predictors of outcome in patients with concomitant functional mitral regurgitation at the time of aortic valve replacement.

BACKGROUND: Concomitant functional mitral regurgitation (FMR) in patients undergoing aortic valve replacement (AVR) is frequently not corrected because it may improve after AVR; however, data supporting this assumption are sparse. We ascertained the impact of clinical and echocardiographic parameters on the outcome of patients with or without concomitant FMR at the time of AVR. METHODS AND RESULTS: Clinical and echocardiographic follow-up was performed on 848 patients who underwent AVR after 1990. Risk factors for mortality and a composite outcome of heart failure (CHF) symptoms, CHF death, or subsequent mitral repair or replacement, were examined with bootstrapped Cox proportional hazard models. Follow-up was 4591 patient-years (mean 5.4+/-3.4 years; maximum 14.2 years). FMR > or = 2+ had no independent adverse effect on survival in patients with aortic stenosis (AS) or insufficiency (AI). However, AS patients with FMR > or = 2+ and 1 additional risk factor (left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation) were at increased risk for the composite outcome (hazard ratio [HR]: 2.7; P=0.004). AI patients with FMR > or = 2+ and a left ventricular end-systolic diameter <45 mm were also at risk (HR: 4.0; P=0.02). Clinical risk factors in the AS and AI subgroups were associated with an increased likelihood of mitral regurgitation > or = 2+ at 18 months postoperatively. CONCLUSIONS: AS patients with FMR > or = 2+ and a left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation have a significantly higher risk of CHF and persistent mitral regurgitation after AVR than other AS patients. AI patients with FMR > or = 2+ and a left ventricular end-systolic diameter <45 mm preoperatively are also at increased risk. Others fare well after AVR.

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PubMed2006

Tissue-engineered injectable collagen-based matrices for improved cell delivery and vascularization of ischemic tissue using CD133+ progenitors expanded from the peripheral blood.

BACKGROUND: The use of stem and/or progenitor cells to achieve potent vasculogenesis in humans has been hindered by low cell numbers, implant capacity, and survival. This study investigated the expansion of CD133+ cells and the use of an injectable collagen-based tissue engineered matrix to support cell delivery and implantation within target ischemic tissue. METHODS AND RESULTS: Adult human CD133+ progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133- cell fractions, and delivered within an injectable collagen-based matrix into the ischemic hindlimb of athymic rats. Controls received injections of phosphate-buffered saline, matrix, or CD133+ cells alone. Immunohistochemistry of hindlimb muscle 2 weeks after treatment revealed that the number of CD133+ cells retained within the target site was >2-fold greater when delivered by matrix than when delivered alone (P<0.01). The transplanted CD133+ cells incorporated into vascular structures, and the matrix itself also was vascularized. Rats that received matrix and CD133+ cells demonstrated greater intramuscular arteriole and capillary density than other treatment groups (P<0.05 and P<0.01, respectively). CONCLUSIONS: Compared with other experimental approaches, treatment of ischemic muscle tissue with generated CD133+ progenitor cells delivered in an injectable collagen-based matrix significantly improved the restoration of a vascular network. This work demonstrates a novel approach for the expansion and delivery of blood CD133+ cells with resultant improvement of their implantation and vasculogenic capacity.

AC133 Antigen↗

PubMed2006

Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch.

BACKGROUND: The long-term outcomes of patients with low-gradient aortic stenosis (LGAS) after aortic valve replacement (AVR) are poorly defined. The purpose of this study was to define the long-term outcomes of LGAS patients after AVR and to evaluate the potential impact of prosthesis-patient mismatch (PPM) in these patients. METHODS AND RESULTS: A cohort of 664 patients undergoing AVR for aortic stenosis after 1990 were followed-up prospectively with annual clinical assessment and echocardiography (total follow-up 3447 patient-years; mean follow-up 5.2+/-3.3 years). LGAS was defined as an aortic valve area <1.2 cm2, a mean transvalvular pressure gradient <40 mm Hg, and a left ventricular (LV) ejection fraction <50%, and was present in 79 patients. Rates and correlates of survival, freedom from congestive heart failure (CHF), and LV mass regression after AVR were determined using multivariate regression methods. Ten-year survival and freedom from CHF after AVR were 72.7+/-7.5% and 68.2+/-9.5%, respectively, for patients with LGAS, compared with 89.6+/-1.8% and 84.1+/-4.2% for patients without LGAS (hazard ratio [HR] for death and postoperative CHF, 3.1+/-1.1 and 2.7+/-0.9, respectively; P<0.01). In LGAS patients, PPM, defined as an indexed effective orifice area < or = 0.85 cm2/m2, was independently associated with increased rates of CHF (HR, 3.6+/-2.2; P=0.039), impaired LV mass regression (P=0.037), and a trend toward increased late mortality (HR, 3.0+/-1.9; P=0.084). CONCLUSIONS: Patients with LGAS have worse long-term outcomes after AVR compared with patients without LGAS. PPM adversely affects the long-term outcomes of LGAS patients and should be avoided in this population.

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PubMed2006

Generation of CD133+ cells from CD133- peripheral blood mononuclear cells and their properties.

OBJECTIVE: CD133 may be the most specific marker of endothelial progenitor cells (EPCs), which are thought to be largely confined to the bone marrow milieu. This study reports on the phenotypic characterization and functional analysis of human CD133+ cells and their generation from cells in the peripheral circulation. METHODS: Adult human CD133+ and CD133- cells were isolated from peripheral blood mononuclear cells, and the generation of CD133+ cells in culture was attempted using different culture combinations. The phenotypic, migratory, adhesive, and angiogenic properties of the native and generated populations were investigated. RESULTS: In adherent and in suspension culture systems, CD133+ cells also expressing CD34 and VEGFR-2 were successfully derived from a previously CD133- population. The migratory potential of CD133+ cells was enhanced by the presence of the CD133- cells. Also, the CD133+ cells derived from the CD133- cells demonstrated improved adhesion to extracellular matrix and endothelial monolayer substrates, and their contribution to in vitro angiogenesis was enhanced compared to freshly isolated CD133+ cells. CONCLUSIONS: These results demonstrate a source of blood CD133+ cells other than direct mobilization from the bone marrow. Cellular interaction was observed between fractions, with CD133+ cells showing better in vitro function in the presence of CD133- cells. These findings provide a novel source for CD133+ cells and a rationale for the investigation of angiogenic cell recruitment or delivery strategies involving more than one cell type at ischemic sites.

AC133 Antigen↗

PubMed2005

Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells.

OBJECTIVE: Off-pump coronary artery bypass grafting may result in fewer myocardial and vascular complications than on-pump. Although differences in aortic manipulations likely play a role, the systemic responses of endothelial progenitor cells to both types of operations have not been examined. We sought to examine endothelial progenitor cell characteristics after off-pump versus on-pump coronary artery bypass grafting. METHODS: Twenty patients undergoing off-pump or on-pump coronary artery bypass grafting were prospectively enrolled and had endothelial progenitor cells isolated and cultured from their peripheral blood before and 24 hours after surgery. Endothelial progenitor cells were identified by fluorescent dual lectin/low-density lipoprotein binding. Their number, phenotype characteristics, proliferation, migratory function, and viability were determined in a blinded fashion. RESULTS: Patient characteristics and numbers of grafts were equivalent. Endothelial progenitor cells had similar phenotypes between groups before and after surgery. Off-pump and on-pump coronary artery bypass grafting resulted in similar increases in endothelial progenitor cell numbers and showed equivalent proliferation activity. However, endothelial progenitor cell migratory function was higher in off-pump patients (25.3 +/- 5.0 vs 5.0 +/- 1.0 cells per high-powered field for off-pump vs on-pump coronary artery bypass grafting, respectively; P = .04). Postoperative endothelial progenitor cell viability adjusted for preoperative baseline was also higher after off-pump than on-pump coronary artery bypass grafting by 72.4% +/- 14.6% (P = .01). Endothelial progenitor cells of on-pump patients were less viable after surgery than before surgery, whereas the reverse was observed in off-pump patients. CONCLUSIONS: Both on-pump and off-pump coronary artery bypass grafting elicit mobilization of endothelial progenitor cells into the peripheral blood. On-pump coronary artery bypass grafting, however, impairs the migratory function and viability of these vascular repair cells, which are conversely preserved after off-pump surgery. Further work is necessary to determine whether the function and viability of endothelial progenitor cells correlate with vascular outcomes and whether their therapeutic modulation may one day benefit coronary artery bypass grafting patients.

Cell Count↗

PubMed2005

Nitric oxide and the angiogenic response: can we improve the results of therapeutic angiogenesis?

Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dysfunction may play a role in this bench-to-bedside discrepancy has led to further research on the role of endothelial-derived mediators in the angiogenic cascade. One of these mediators is nitric oxide (NO), which plays an integral role in the development and maintenance of a microvascular network and whose local availability is altered in endothelial dysfunction. This article outlines the role of NO in the angiogenic response and discusses possible therapeutic options to optimise endothelial dysfunction and NO availability in patients undergoing angiogenic therapy.

Angiogenesis Inducing Agents↗