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Biomedical subjects

Marc Ruel

Publications and source records attributed to Marc Ruel.

At least 19 recordsLinked to original sources

The "hybrid flip-over" technique for anterior leaflet prolapse repair.

Repair of the anterior mitral leaflet or bi-leaflet prolapse is technically more demanding than repair of the posterior mitral leaflet. Although several techniques have been proposed for the repair of anterior mitral leaflet prolapse during bi-leaflet repair, practical challenges remain, including the determination of the appropriate length for artificial chords. Herein we describe a novel and reproducible technique for bi-leaflet mitral valve repair, including those with extensive anterior mitral leaflet prolapse.

Adult↗

Skeletonized internal thoracic artery harvest reduces pain and dysesthesia and improves sternal perfusion after coronary artery bypass surgery: a randomized, double-blind, within-patient comparison.

BACKGROUND: Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery. METHODS AND RESULTS: Patients (n = 48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n = 7). Skeletonization required longer ITA harvest times (27 +/- 1 versus 24 +/- 1 minutes; P = 0.04). There was a trend toward increased ITA length in the skeletonized group (18.2 +/- 0.3 versus 17.7 +/- 0.3 cm; P = 0.09). In situ ITA flow was lower in skeletonized arteries (7.4 +/- 0.9 versus 10.1 +/- 1.0 mL/min; P = 0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P = 0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17 +/- 6% (P = 0.03) on the skeletonized side. CONCLUSIONS: Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.

Coronary Artery Bypass↗

Mechanical versus bioprosthetic valve replacement in middle-aged patients.

OBJECTIVE: The current trend towards decreasing the age for selection of a tissue over a mechanical prosthesis has led to a dilemma for patients aged 50-65 years. This cohort study examines the long-term outcomes of mechanical versus bioprosthetic valves in middle-aged patients. METHODS: Patients (N = 659) aged between 50 and 65 years who had first-time aortic valve replacement (AVR) and/or mitral valve replacement (MVR) with contemporary prostheses were followed prospectively after surgery. The total follow-up was 3,402 patient-years (mean 5.1 +/- 4.1 years; maximum 18.3 years). Outcomes were examined with multivariate actuarial methods. A composite outcome of major adverse prosthesis-related events (MAPE) was defined as the occurrence of reoperation, endocarditis, major bleeding, or thromboembolism. RESULTS: Ten-year survival was 73.2 +/- 4.2% after mechanical AVR, 75.1 +/- 12.6% after bioprosthetic AVR, 74.1 +/- 4.6% after mechanical MVR, and 77.9 +/- 7.4% after bioprosthetic MVR (P=NS). Ten-year reoperation rates were 35.4% and 21.3% with aortic and mitral bioprostheses, respectively. Major bleeding occurred more often following mechanical MVR (hazard ratio [HR]: 3.3; 95% confidence interval [CI] 1.2, 9.0; P = 0.022), and the incidence of any thromboembolic event was more common after mechanical MVR (HR: 4.7; CI 1.4, 13.3; P = 0.01). Overall freedom from MAPE at 10 years was 70.2 +/- 4.1% for mechanical AVR patients, 41.0+/-30.3% for bioprosthetic AVR patients, 53.3 +/- 8.8% for mechanical MVR patients, and 61.2 +/- 9.2% for bioprosthetic MVR patients. Although a trend existed towards more MAPE amongst middle-age patients with tissue valves, multivariate analysis did not identify the presence of a bioprosthesis as an independent risk factor for MAPE (HR: 1.3; CI 0.9, 2.0; P = 0.22). CONCLUSIONS: In middle-aged patients, MAPE may occur more often in patients with bioprosthetic valves, but definitive conclusions necessitate the accumulation of additional follow-up. At present, these data do not support lowering the usual cutoff for implantation of a tissue valve below the age of 65.

Aged↗

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.

Aged↗

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↗

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.

Aged↗

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↗

Prosthesis-patient mismatch after aortic valve replacement predominantly affects patients with preexisting left ventricular dysfunction: effect on survival, freedom from heart failure, and left ventricular mass regression.

OBJECTIVE: The effect of prosthesis-patient mismatch on clinical outcome and left ventricular mass regression after aortic valve replacement remains controversial. Data on whether the clinical effect of prosthesis-patient mismatch depends on left ventricular function at the time of aortic valve replacement are lacking. This study examined the long-term clinical and echocardiographic effects of prosthesis-patient mismatch in patients with and without left ventricular systolic dysfunction at the time of aortic valve replacement. METHODS: Preoperative and serial postoperative echocardiograms were performed in 805 adults who underwent aortic valve replacement between 1990 and 2003 and who were subsequently followed up in a dedicated valve clinic (follow-up, mean +/- SD, 5.5 +/- 3.5 years; maximum, 14.2 years). Preoperative left ventricular function was defined as normal (ejection fraction > or =50%) in 548 patients and impaired (ejection fraction <50%) in 257 patients. RESULTS: Patients with impaired preoperative left ventricular function and prosthesis-patient mismatch (indexed effective orifice area < or =0.85 cm2/m2) had a decreased overall late survival (hazard ratio, 2.8; P = .03), decreased freedom from heart failure symptoms or heart failure death (odds ratio of 5.1 at 3 years after aortic valve replacement; P = .009), and diminished left ventricular mass regression compared with patients with impaired preoperative left ventricular function and no prosthesis-patient mismatch. These effects of prosthesis-patient mismatch were not observed in patients with normal preoperative left ventricular function. CONCLUSIONS: Prosthesis-patient mismatch at an indexed effective orifice area of 0.85 cm2/m2 or less after aortic valve replacement primarily affects patients with impaired preoperative left ventricular function and results in decreased survival, lower freedom from heart failure, and incomplete left ventricular mass regression. Patients with impaired left ventricular function represent a critical population in whom prosthesis-patient mismatch should be avoided at the time of aortic valve replacement.

Aged↗

Off-pump coronary surgery through mini-incisions: is it reasonable?

PURPOSE OF REVIEW: Coronary artery bypass grafting as currently performed is considered the gold standard of coronary revascularization. It also, however, is a potential source of complications, especially in patients with multiple co-morbid risk factors. To alleviate some of these downsides, cardiac surgeons designed minimally invasive procedures performed off-pump, without sternotomy, and through small incisions. The efficacy of these techniques is emerging in the literature. Our aim is to describe the new technique that we are using, and provide an objective review of the recent literature with regards to safety and related surgical outcomes. RECENT FINDINGS: Although no long-term follow-up data exist yet with respect to the specific technique described herein, current evidence suggests that both on-pump and off-pump coronary bypass grafting techniques, when done in experienced centers, provide similar rates of completeness of revascularization, long-term patency, and freedom from surgical reintervention. When applied to patients at high surgical risk, observational studies suggest a decrease in the incidence of stroke, bleeding, renal complications, and mortality with off-pump bypass grafting. SUMMARY: Cardiac surgery performed off-pump without sternotomy is a procedural extension of off-pump bypass grafting which has the potential to be as safe as conventional coronary bypass grafting. The technique could offer an advantage to the high-risk patient population, or to patients for whom return to physically demanding work must be expedient after surgery.

Coronary Artery Bypass, Off-Pump↗

Angiogenesis for the treatment of inoperable coronary disease: the future.

Improved treatment options and better management of cardiovascular risk factors have resulted in improved outcomes for patients suffering from severe coronary artery disease. However, coronary artery disease may be of such a diffuse and severe manner that repeated attempts at catheter-based interventions and coronary artery bypass grafting may be unsuccessful at restoring normal myocardial blood flow. It is the goal of therapeutic angiogenesis to restore perfusion to chronically ischemic myocardium using protein growth factors, gene therapy, or, more recently, cell-based therapy, without intervening on the epicardial coronary arteries. However, angiogenesis has not yet provided significant clinical benefit and is still reserved as an experimental treatment for patients who have failed conventional therapies. Once potential endogenous inhibitors of vascular development can be modified, angiogenesis may become more useful for therapeutic purposes. It is hoped that angiogenesis for therapeutic purposes will one day effectively re-create the potent natural processes of vascularization that every human being undergoes during growth and development and become a major modality for the treatment of coronary artery disease.

Angiogenic Proteins↗

Combined atrial fibrillation ablation with mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the efficacy and outcome of radiofrequency (RF) atrial fibrillation (AF) ablation in patients undergoing mitral valve (MV) surgery. METHODS: Between March 2002 and December 2004, 61 patients (mean age 65.4 +/- 10 years) underwent isolated endo-left atrial AF ablation using a unipolar RF device (Cardioblate; Medtronic, USA) in conjunction with 34 MV repairs and 27 MV replacements. AF was paroxysmal in 13 patients (21%), and permanent in 48 (79%), with a mean duration of 3.6 +/- 3.5 years. The etiology was degenerative in 35 patients (57%), rheumatic in 17 (28%), and ischemic in nine (17%). All patients received amiodarone postoperatively. RESULTS: No patients died during the study, and there were no thromboembolic complications. All patients had intraoperative conversion. Forty-one patients (67%) presented with postoperative relapse; definitive conversion was achieved in 34 (83%) cases within three months. The overall success rate was 75.4% at 14 +/- 8.8 months; success was greater in the MV repair group (85%) than in the MV replacement group (66.7%), though not significantly so (p = 0.09). Factors associated with definitive conversion included smaller left atrial size (p = 0.007), decreased left ventricular end-diastolic diameter (p = 0.04), and NYHA class I (p = 0.05). Age, AF duration and etiology were not associated with conversion, but associated coronary artery bypass grafting showed a strong trend towards significance (p = 0.07). In these patients, AF duration did not predict conversion to sinus rhythm. CONCLUSION: Combined AF ablation with MV surgery is safe and effective. Although AF ablation seems more beneficial with MV repair, the success rate may vary significantly according to patient characteristics.

Aged↗

Mortality and myocardial infarction following surgical versus percutaneous revascularization of isolated left anterior descending artery disease: a meta-analysis.

OBJECTIVE: Despite numerous studies comparing surgical versus percutaneous revascularization, the optimal treatment of patients with isolated left anterior descending (LAD) artery disease remains debated. We conducted a meta-analysis to study the early and mid-term outcomes following percutaneous and surgical treatment of isolated LAD disease. METHODS: Medline, EMBASE, and the Cochrane databases were searched and a hand search of bibliographies was conducted. Clinical data was extracted independently by two individuals. Random effects models were used to calculate pooled risk ratios (RR) and meta-regression was employed to explain study heterogeneity. Stratified analyses were conducted and a Funnel plot was used to assess publication bias. RESULTS: Eight randomized trials (1110 patients; median follow-up: 2.1 years, range: 0.5-5 years) and nine observational studies (12,209 patients; median follow-up: 3 years, range: 0.5-5.5 years) were identified and analyzed separately. Both randomized and observational studies demonstrated a beneficial effect of surgery compared to percutaneous therapy on mid-term major adverse cardiac events (MACE) (RR [95% CI]: 0.33 [0.24-0.46] for randomized and 0.32 [0.24-0.41] for observational studies). Studies with >1 year of follow-up demonstrated a beneficial effect of surgery compared to percutaneous therapy on combined mortality and MI rates for randomized (RR [95% CI]: 0.59 [0.35-0.98]) and observational studies (RR [95% CI]: 0.81 [0.65-0.99]). The start year was identified as a source of study heterogeneity. CONCLUSIONS: Surgical treatment of isolated LAD disease is associated with reduced MACE, reduced mortality, and MI rates at mid-term follow-up, as well as lower recurrence of angina. Evolution of treatment strategies may explain some of the variability between studies.

Angioplasty, Balloon, Coronary↗

The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423].

BACKGROUND: Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery. METHODS: Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery. DISCUSSION: This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.

Journal Article↗

Effects of L-arginine on fibroblast growth factor 2-induced angiogenesis in a model of endothelial dysfunction.

BACKGROUND: Nitric oxide availability, which is decreased in advanced coronary artery disease associated with endothelial dysfunction, is an important mediator of fibroblast growth factor-2 (FGF-2)-induced angiogenesis. This could explain the disappointing results of FGF-2 therapy in clinical trials despite promising preclinical studies. We examined the influence of L-arginine supplementation to FGF-2 therapy on myocardial microvascular reactivity and perfusion in a porcine model of endothelial dysfunction. METHODS AND RESULTS: Eighteen pigs were fed either a normal (NORM, n=6) or high cholesterol diet, with (HICHOL-ARG, n=6) or without (HICHOL, n=6) L-arginine. All pigs underwent ameroid placement on the circumflex artery and 3 weeks later received surgical FGF-2 treatment. Four weeks after treatment, endothelial-dependent coronary microvascular responses and lateral myocardial perfusion were assessed. Endothelial cell density was determined by immunohistochemistry. FGF-2, fibroblast growth receptor-1, endothelial-derived nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and syndecan-4 levels were determined by immunoblotting. Pigs from the HICHOL group showed endothelial dysfunction in the circumflex territory, which was normalized by L-arginine supplementation. FGF-2 treatment was ineffective in the HICHOL group (circumflex/left anterior descending blood flow ratios: 1.01 (rest) and 1.01 (pace), after and before treatment). Addition of L-arginine improved myocardial perfusion in response to FGF-2 at rest (ratio 1.13, P=0.02 versus HICHOL) but not during pacing (ratio 0.94, P=NS), and was associated with increased protein levels of iNOS and eNOS. CONCLUSIONS: L-arginine supplementation can partially restore the normal response to endothelium-dependent vasorelaxants and myocardial perfusion in response to FGF-2 treatment in a swine model of hypercholesterolemia-induced endothelial dysfunction. These findings suggest a role for L-arginine in combination with FGF-2 therapy for end-stage coronary artery disease.

Angiogenesis Inducing Agents↗

Percutaneous mitral valve repair for chronic ischemic mitral regurgitation: a real-time three-dimensional echocardiographic study in an ovine model.

BACKGROUND: Although surgical annuloplasty is the standard repair for ischemic mitral regurgitation (IMR), its application is limited by high morbidity and mortality. Using 2D and real-time 3D echocardiography in an ovine model of chronic IMR, we evaluated the geometric impact and short-term efficacy of a percutaneous transvenous catheter-based approach for mitral valve (MV) repair using a novel annuloplasty device placed in the coronary sinus. METHODS AND RESULTS: Six sheep developed IMR 8 weeks after induced posterior myocardial infarction. An annuloplasty device optimized to reduce anterior-posterior (A-P) mitral annular dimension and MR was placed percutaneously in the coronary sinus. Mitral annular A-P and commissure-commissure dimensions and MV tenting area (MVTa) in 3 parallel A-P planes (medial, central, and lateral) were assessed by real-time 3D echocardiography with 3D software. The annuloplasty device reduced MR jet area from 5.4+/-2.6 to 1.3+/-0.9 cm2 (P<0.01), mitral annular A-P dimension in both systole and diastole (24.3+/-2.5 to 19.7+/-2.4 mm; P<0.03; 31.0+/-3.9 to 24.7+/-2.1 mm; P<0.001), and MVTa at mid systole in all 3 planes (153+/-46 to 93+/-24 mm2, P<0.01; 140+/-47 to 88+/-23 mm2, P<0.03; and 103+/-23 to 87+/-26 mm2, P<0.03). CONCLUSIONS: Percutaneous coronary sinus-based mitral annuloplasty reduces chronic IMR by reducing mitral annular A-P diameter and MVTa. This suggests the potential clinical application of a new nonsurgical therapeutic approach in patients with IMR.

Animals↗

Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) induces derangements in physiology characterized by activation of blood pathways that may contribute to multiorgan dysfunction. This trial addresses the efficacy of a biocompatible surface alone and in combination with steroids in inhibiting these changes. METHODS: In a factorial design, patients undergoing coronary artery bypass grafting were randomized (four groups; n = 17 per group) to CPB utilizing control circuits or a circuit prepared with a surface modifying active copolymer (SMA-CPB), with or without methylprednisolone (MPSS, 1 g intravenous). Leukocyte and complement activation, cytokine release, and bradykinin generation were measured. Clinical outcomes (blood loss, transfusion, arterial pressure response, and postoperative cardiac and pulmonary functions) were also examined. RESULTS: The SMA-CPB was associated with a significant inhibition of elastase release (p = 0.026) and bradykinin generation (p = 0.027) during CPB. Terminal complement complex (TCC) generation was inhibited as an effect of SMA-CPB (p = 0.047). There was an interaction of SMA-CPB and MPSS to decrease both TCC (p = 0.042) and bradykinin generation (p = 0.028). There were strong effects of MPSS in inhibiting release of interleukin 6 (IL-6) (p = 0.007) and IL-8 (p < 0.001) and tissue plasminogen activator over time (p = 0.009) as well as decreasing peak day 1 creatine kinase (CK, p = 0.015) levels. Clinical effects of MPSS included decreased atrial fibrillation (p = 0.02), improved cardiac index over time, increased pulmonary compliance, and increased insulin need. CONCLUSIONS: This trial suggests a potential beneficial effect for combined strategies to minimize inflammation after CPB. The specific effect of MPSS in decreasing postoperative atrial fibrillation and CK warrants further investigation of its role as a potential myocardial protective agent.

Biomarkers↗