Water-suppression cycling 3-T cardiac 1 H-MRS detects altered creatine and choline in patients with aortic or mitral stenosis.

Cardiac proton spectroscopy (1 H-MRS) is widely used to quantify lipids. Other metabolites (e.g. creatine and choline) are clinically relevant but more challenging to quantify because of their low concentrations (approximately 10 mmol/L) and because of cardiac motion. To quantify cardiac creatine and choline, we added water-suppression cycling (WSC) to two single-voxel spectroscopy sequences (STEAM and PRESS). WSC introduces controlled residual water signals that alternate between positive and negative phases from transient to transient, enabling robust phase and frequency correction. Moreover, a particular weighted sum of transients eliminates residual water signals without baseline distortion. We compared WSC and the vendor's standard 'WET' water suppression in phantoms. Next, we tested repeatability in 10 volunteers (seven males, three females; age 29.3 ± 4.0 years; body mass index [BMI] 23.7 ± 4.1 kg/m2 ). Fat fraction, creatine concentration and choline concentration when quantified by STEAM-WET were 0.30% ± 0.11%, 29.6 ± 7.0 µmol/g and 7.9 ± 6.7 µmol/g, respectively; and when quantified by PRESS-WSC they were 0.30% ± 0.15%, 31.5 ± 3.1 µmol/g and 8.3 ± 4.4 µmol/g, respectively. Compared with STEAM-WET, PRESS-WSC gave spectra whose fitting quality expressed by Cramér-Rao lower bounds improved by 26% for creatine and 32% for choline. Repeatability of metabolite concentration measurements improved by 72% for creatine and 40% for choline. We also compared STEAM-WET and PRESS-WSC in 13 patients with severe symptomatic aortic or mitral stenosis indicated for valve replacement surgery (10 males, three females; age 75.9 ± 6.3 years; BMI 27.4 ± 4.3 kg/m2 ). Spectra were of analysable quality in eight patients for STEAM-WET, and in nine for PRESS-WSC. We observed comparable lipid concentrations with those in healthy volunteers, significantly reduced creatine concentrations, and a trend towards decreased choline concentrations. We conclude that PRESS-WSC offers improved performance and reproducibility for the quantification of cardiac lipids, creatine and choline concentrations in healthy volunteers at 3 T. It also offers improved performance compared with STEAM-WET for detecting altered creatine and choline concentrations in patients with valve disease.

Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling.

INTRODUCTION: Mitral valve disease (MVD), including mitral valve regurgitation (MR) and mitral valve stenosis (MS), is a chronic and progressive cardiac malady. However, the metabolic alterations in MVD is not well-understood till now. The current gold standard diagnostic test, transthoracic echocardiography, has limitations on high-throughput measurement and lacks molecular information for early diagnosis of the disease. OBJECTIVE: The present study aimed to investigate the biochemical alterations and to explore their diagnostic potential for MVD. METHODS: Plasma metabolic profile derangements and their diagnostic potential were non-invasively explored in 34 MR and 20 MS patients against their corresponding controls, using high-throughput NMR-based untargeted metabolomics. RESULTS: Eighteen differential metabolites were identified for MR and MS patients respectively, on the basis of multivariate and univariate data analysis, which were mainly involved in energy metabolism, amino acid metabolism, calcium metabolism and inflammation. These differential metabolites, notably the significantly down-regulated formate and lactate, showed high diagnostic potential for MVD by using Spearman's rank-order correlation analysis and ROC analysis. CONCLUSIONS: To the best of our knowledge, the present study is the first one that explores the metabolic derangements and their diagnostic values in MVD patients using metabolomics. The findings indicated that metabolic disturbance occurred in MVD patients, with plasma formate and lactate emerged as important candidate biomarkers for MVD.

Association of matrix metalloproteinase 3 and endogenous inhibitors with inflammatory markers in mitral valve disease and calcification.

Calcific mitral valve stenosis (MVS) is a common disease characterized by extensive remodeling of the extracellular matrix via matrix metalloproteinases (MMPs). The mechanism of calcification due to extensive matrix remodeling remains unclear. In this study, we investigated the relationship between MMP-3, tissue inhibitors of metalloproteinases (TIMPs) as well as pro-inflammatory cytokines and the phenomenon of calcification in MVS. 212 patients having rheumatic mitral stenosis (RMS) and 155 healthy control subjects were recruited in the Cardiology Department of La Rabta Hospital University. Levels of MMP-3, TIMPs, IL-6 and TNF-α were measured by ELISA sandwich assay, hs-CRP was measured by immunoturbidimetry. Plasma levels of MMP-3, TIMP-1 and MMP-3/TIMP-2 ratio were lower only in RMS women in comparison to the control group. Calcification degree correlated positively with MMP-3 in women and men. In addition, calcification was correlated positively with MMP-3/TIMPs ratio in women patients. The inflammatory parameters were positively associated with extracellular matrix turnover biomarkers in men patients. In patients, the level of MMP-3 was increased in men and women with a calcification score ≥ 5. In addition, MMP-3 level predicted the occurrence of calcification. At ROC curves analysis, the cut-off MMP-3 level was in women was 9.21 ng/ml (sensitivity 51.1%, specificity 89.3%) and in men was 12.84 ng/ml (sensitivity 78.6%, specificity 77.8%). The high levels of MMP-3 and the biomarkers of inflammation contribute to valvular remodeling and calcification of the mitral valve.

DNA methylation dysregulations in rheumatic heart valve disease.

BACKGROUND: The epigenetic changes underlying the development of rheumatic heart valve disease (RHVD) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of RHVD. In the present study, we evaluated the DNA methylation dysregulations from myocardial tissue in RHVD patients systematically. METHODS: Right atrial myocardial tissue obtained from rheumatic valvular patients who had undergone valve replacements surgery (n = 73) and were compared to healthy controls (n = 4). the promoter methylation level of Intercellular adhesion molecule-1 (ICAM-1) gene and its correlation with ICAM-1 mRNA expression level, the global DNA methylation level and its correlation with age and mRNA expression level of DNA methyltransferase (DNMT) genes were detected. RESULTS: The ICAM-1 mRNA expression was increased (healthy control vs. NHYA III, 0.70 ± 0.19 vs. 4.38 ± 3.19, p = 0.011; NYHA IIvs. NHYA III, 2.60 ± 1.99 vs. 4.38 ± 3.19, p = 0.008) and the ICAM-1 gene was hypomethylated in RHVD patients (healthy controls vs. NYHA II, 0.120 ± 0.011 vs. 0.076 ± 0.057, p = 0.039; healthy control vs. NHYA III, 0.120 ± 0.011 vs. 0.041 ± 0.022, p < 0.001; NYHA IIvs. NHYA III, 0.076 ± 0.057 vs. 0.041 ± 0.022, p < 0.001). Meanwhile, The ICAM-1 mRNA expression level has negative correlation with the mean methylation level in the promoter region of ICAM-1 gene (r = -0.459, p < 0.001). The global DNA methylation levels was significantly increased in RHVD patients than in healthy controls (healthy control vs. NHYA III, 0.77 ± 0.28 vs. 2.09 ± 1.20, p = 0.017; NYHA IIvs. NHYA III, 1.57 ± 0.78 vs. 2.09 ± 1.20, p = 0.040) and had positive correlation with age (r = 0.326, p = 0.005), especially for older age group (≥ 60 years). DNMT1 likely plays an essential role in the DNA dysregulations in RHVD patients. CONCLUSIONS: Our analysis revealed that DNA methylation dysregulations may be relevant in the pathogenesis of RHVD.

New integrated approach to percutaneous mitral valvuloplasty combining Wilkins score with commissural calcium score and commissural area ratio.

BACKGROUND: Present echocardiographic scoring systems for percutaneous mitral valvuloplasty (PMV) have limitations, and no scoring system is significant determinant of procedural outcome. In this study, we assess the relationship between various echocardiographic parameters and scoring systems with immediate outcomes and test an integrated approach by combining Wilkins score with other parameters. METHODS: One hundred two patients who had undergone PMV were included in this prospective observational study. Preprocedural mitral valve morphology was assessed and categorized using Wilkins score, Sutaria scoring system, and Nunes quantitative scoring system. RESULTS: Optimal PMV results were obtained in 84 patients (82.35%), and suboptimal PMV results were obtained in 18 patients (17.65%). Using Nunes scoring system, suboptimal PMV results were obtained in 9 (37.5%) patients of high-risk group (n=24), 8 (13.8%) of intermediate-risk group (n=58), and one (5%) patient of low-risk group (n=20). Using Wilkins scoring system, in patients having score>8 (n=16) suboptimal results were obtained in 5 (31.7%) and in patients having score<8 (n=86) suboptimal results were obtained in 13 (15.1%). Using Sutaria scoring system, in patients having score 3 to 4 (low risk, n=68) suboptimal results were obtained in 6 (8.8%), and in patients having score 0-2 (high risk, n=34) suboptimal results were obtained in 12 (35.3%) patients. CONCLUSION: All echocardiographic scores have significant limitations, and an integrative approach is mandatory. Combining traditional Wilkins score with Sutaria score and commissural area ratio better predicts procedural outcomes.

Histopathological Study of Left and Right Atria in Isolated Rheumatic Mitral Stenosis With and Without Atrial Fibrillation.

BACKGROUND: Mitral stenosis (MS) has the highest incidence of atrial fibrillation (AF) in chronic rheumatic valvular disease. There are very few studies in isolated MS comparing histopathological changes in patients with sinus rhythm (SR) and AF. OBJECTIVES: To analyze the histological changes associated with isolated MS and compare between changes in AF and SR. METHODS: This was a prospective study in patients undergoing valve replacement surgery for symptomatic isolated MS who were divided into 2 groups, Group I AF (n = 13) and Group II SR (n = 10). Intra-operative biopsies performed from 5 different sites from both atria were analyzed for 10 histopathologic changes commonly associated with AF. RESULTS: On multivariate analysis, myocytolysis (odds ratio [OR]: 1.48, P = 0.05) was found to be associated with AF, whereas myocyte hypertrophy (OR: 0.21, P = 0.003), and glycogen deposition (OR: 0.43, P = 0.002) was associated with SR. Interstitial fibrosis the commonest change was uniformly distributed across both atria irrespective of the rhythm. CONCLUSION: In rheumatic MS, SR is associated with myocyte hypertrophy whereas AF is associated with myocytolysis. Endocardial inflammation is more common in left atrial appendage irrespective of rhythm. Interstitial fibrosis is seen in >90% of patients distributed in both the atria and is independent of the rhythm. Amyloid and Aschoff bodies are uncommon and the rest of the changes are uniformly distributed across both the atria.

Contractile properties of the right atrial myofilaments in patients with myxomatous mitral valve degeneration.

BACKGROUND: Myxomatous degeneration of the mitral valve is a common pathological finding in mitral valve surgery and the most common reason for severe mitral valve regurgitation. Considering the importance of right ventricular remodeling and global function after mitral valve surgery we tried to elucidate a possible association of myxomatous mitral valve and impairment of right atrial and ventricular function, which might have an impact on global ventricular performance after mitral valve surgery. METHODS: Right atrial tissue was harvested from 47 patients undergoing mitral valve surgery. We took the trabeculae from the right auricle, which was resected at the right auricle for implementation of extracorporal circulation. The tissue was skinned and prepared in a 24 h-lasting procedure to create small fibers for hinging them in the "muscle machine", an experimental set-up, created for pCa-force measurements. RESULTS: Patients without myxomatous mitral valve developed significantly more force (4.0 mN ± 0.8 mN) at the highest step of calcium concentration compared to 2.7 mN ± 0.4 mN in group of patients with myxomatous valve degeneration (p 0.03). Calcium sensitivity in the myxomatous valve group was at pCa 6.0 and in the non-myxomatous group at pCa 5. Furthermore we observed a significant difference in ejection fraction (EF) among the groups: 49% in the non-myxomatous group versus 57% in the myxomatous group (p 0.03). In the non-myxomatous group 5 patients had diastolic dysfunction grade I-II (22,7%), in group I 10 patients (40%). This was also significant (p 0.04). CONCLUSIONS: Patients with myxomatous mitral valve degeneration seem to have reduced force capacities. Calcium sensitivity is higher compared to the non-myxomatous group, which might be a compensatory mechanism to cover the physiological demand. Furthermore we suggest a higher incidence of diastolic dysfunction in patients with myxomatous mitral valve degeneration, which might have an impact on ventricular remodeling after mitral valve surgery.

Systemic and local levels of fetuin-a in calcified mitral valves of rheumatic heart disease.

BACKGROUND AND AIM OF THE STUDY: Fetuin-A is a circulating glycoprotein that inhibits ectopic calcification. The study aim was first, to assess serum fetuin-A level in patients with calcified rheumatic mitral valve disease (RMVD), and second, to demonstrate the presence of fetuin-A by immunohistochemistry (IHC) in calcified RMVD which, to date, has not been verified in other studies. METHODS: The study group comprised 68 adult patients with isolated RMVD and normal renal function. Of these patients, 34 (27 males, seven females; mean age 33.44 +/- 9.0 years) had severe calcification (Wilkins calcium score 3 or 4) and 34 (25 males, nine females; mean age 30.8 +/- 8.5 years) had mild calcification (Wilkins calcium score 1 or 2). A group of 32 age- and gender-matched healthy subjects (25 males, seven females; mean age 29.5 +/- 4.6 years) served as controls. Baseline serum fetuin-A levels were measured using an enzyme-linked immunosorbent assay (ELISA), while Wilkins calcium scores were assessed using either transthoracic or transesophageal echocardiography. Serum levels of calcium, phosphorus and alkaline phosphatase were assessed in all subjects. Histopathological examinations of ten severely calcific rheumatic mitral valves were made and compared with 10 non-calcified rheumatic mitral valves, all of which had undergone mitral valve replacement. RESULTS: Serum fetuin-A levels were significantly lower in RMVD patients than in controls (108.83 +/- 7.1 versus 114.46 +/- 3.32 ng/ml; p = 0.014). However, there was no significant difference in fetuin-A level between patients with severe (C3/C4) versus mild calcification (C1/C2) (108.84 +/- 7.82 versus 108.82 +/- 6.36 ng/ml; p = NS). No correlation of fetuin-A was seen with serum high-sensitivity C-reactive protein, calcium, phosphorus and alkaline phosphatase, or with Wilkins' calcium score. IHC analyses revealed the presence of fetuin-A in the mesenchymal matrix and calcified area of calcific valves, while minimal to absent fetuin-A deposition was detected in the mesenchymal matrix of non-calcified mitral valves. CONCLUSION: Serum fetuin-A levels were significantly decreased in patients with calcific RMVD. The present study was the first to demonstrate fetuin-A in the calcified mitral valve of rheumatic etiology, and suggests its possible role in the pathophysiology of calcific mitral valve disease. Further studies are required, however, to determine therapeutic implications.

Comparative study of human aortic and mitral valve interstitial cell gene expression and cellular function.

Valve interstitial cells (VICs) are essential for valvular pathogenesis. However, the transcriptional profiles and cellular functions of human aortic VICs (hAVICs) and mitral VICs (hMVICs) have not been directly compared. We performed NimbleGen gene expression profiling analyses of hAVICs and hMVICs. Seventy-eight known genes were differentially expressed between hAVICs and hMVICs. Higher expression of NKX2-5, TBX15, OGN, OMD, and CDKN1C and lower expression of TBX5, MMP1, and PCDH10 were found in hAVICs compared to hMVICs. The differences in these genes, excepting OGN and OMD, remained in rheumatic VICs. We also compared cell proliferation, migration, and response to mineralization medium. hMVICs proliferated more quickly but showed more calcium deposition and alkaline phosphatase activity than hAVICs after culture in mineralization medium, indicating that hMVICs were more susceptible to in vitro calcification. Our findings reveal differences in the transcription profiles and cellular functions of hAVICs and hMVICs.

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function.

Mitral valve endothelial cells are important for maintaining lifelong mitral valve integrity and function. Plasma endothelial microparticles (EMPs) increased in various pathological conditions related to activation of endothelial cells. However, whether EMPs will increase in mitral valve disease and their relationship remains unclear. Here, 81 patients with mitral valve disease and 45 healthy subjects were analyzed for the generation of EMPs by flow cytometry. Human mitral valve endothelial cells (HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O(2)(∙-)) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O(2)(∙-) generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease.

MicroRNA expression signature in atrial fibrillation with mitral stenosis.

The aim of this study was to investigate the microRNA (miRNA) signature in atrial fibrillation (AF) with mitral stenosis (MS). miRNA arrays were used to evaluate the expression signature of the right atrial appendages of healthy individuals (n=9), patients with MS and AF (n=9) and patients with MS without AF (n=4). The results were validated with qRT-PCR analysis. GOmir was used to predict the potential miRNA targets and to analyze their functions. DIANA-mirPath was used to incorporate the miRNAs into pathways. miRNA arrays revealed that 136 and 96 miRNAs were expressed at different levels in MS patients with AF and in MS patients without AF, respectively, compared with healthy controls. More importantly, 28 miRNAs were expressed differently in the MS patients with AF compared with the MS patients without AF; of these miRNAs, miR-1202 was the most dysregulated. The unsupervised hierarchical clustering analysis based on the 28 differently expressed miRNAs showed that the heat map of miRNA expression categorized two well-defined clusters that corresponded to MS with AF and MS without AF. The qRT-PCR results correlated well with the microarray data. Bioinformatic analysis indicated the potential miRNA targets and molecular pathways. This study shows that there is a distinct miRNA expression signature in AF with MS. The findings may be useful for the development of therapeutic interventions that are based on rational target selection in these patients.

Copeptin level and copeptin response to percutaneous balloon mitral valvuloplasty in mitral stenosis.

We aimed to investigate copeptin levels in mitral stenosis (MS) patients and the behavior of copeptin after hemodynamic improvement achieved by percutaneous balloon mitral valvuloplasty (PBMV). The study involved 29 consecutive symptomatic patients with moderate to severe rheumatic MS who underwent PBMV. Twenty-eight age- and gender-matched healthy volunteers composed the control group. Blood samples for copeptin were obtained immediately before and 24 h after PBMV, centrifuged, then stored at -70°C until assayed. The copeptin level of the patient group was statistically different from that of the control group (61.8 ± 34.4 and 36.8 ± 15.2 pg/ml, respectively; p = 0.001). PBMV resulted in a significant increase in mitral valve area and a significant decrease in transmitral gradient as well as systolic pulmonary artery pressure. While hemodynamic relief was obtained, we detected a statistically significant decline in copeptin levels 24 h after PBMV compared to the baseline levels (from 61.8 ± 34.4 to 44.1 ± 18.2 pg/ml; p = 0.004).

Alterations in calcium regulatory protein expression in patients with preserved left ventricle systolic function and mitral valve stenosis.

BACKGROUND: In heart failure, alterations in the expression of proteins relevant to calcium homeostasis are involved in depressed contractility and diminished relaxation. However the regulation of genes expression is only partially known. The aim was to assess expression of calcium regulatory proteins in left ventricle (LV) myocardium characterised by a preserved global function in mitral valve stenosis (MVS) model but increased neurohumoral/cytokine (N/C) activation. METHODS AND RESULTS: Plasma N/C activation was evaluated in MVS-patients (n = 27), where expression of calcium regulatory proteins (L-type channel, sarcoplasmic reticulum Ca2+-ATPase type2 - SERCA2, Na+/Ca2+ exchanger -NCX, calsequestrin, phospholamban) in LV myocardium was assessed (Western Blot) in comparison with non-failing hearts (NFH). Out of all proteins assessed in MVS, only SERCA2 and NCX expression revealed highly variable changes between subjects, with significant reduction of SERCA2 (15%) level compared to NFH. Moreover, SERCA2 was negatively correlated with BNP (univariate/regression analysis r = -0.63, P = 0.005/r2 = 0.74, P <0.001, respectively), whereas NCX was positively correlated only with noradrenaline (univariate/stepwise analysis r = 0.59 P = 0.002/r2 = 0.59; P = 0.003). CONCLUSIONS: In MVS-patients LV becomes remodelled, although its global function is preserved. It seems that apart from alterations in LV load and wall stress, also such neurohumoral factors as BNP/noradrenaline may influence the Ca2+ handling proteins expression.

Late mitral restenosis after percutaneous commissurotomy: Predictive value of inflammation and extracellular matrix remodeling biomarkers.

BACKGROUND: The role of chronic inflammation in mitral restenosis after percutaneous mitral commissurotomy (PMC) is still controversial. AIMS: We sought to assess the predictive value of inflammation and extracellular matrix (ECM) remodeling biomarkers in late mitral restenosis after PMC. METHODS: We prospectively enrolled 155 patients (mean age 46.2±11 years) with at least 5 year follow up after primary PMC. Serum levels of high sensitive C-Reactive Protein (hs-CRP), matrix metalloproteinases MMPs, tissue-specific inhibitors of matrix metalloproteinases TIMPs, and tumor necrosis factor α (TNFα)] were measured. RESULTS: Late mitral restenosis occurred in 55 patients (35.5%). The independent predictors of late mitral stenosis were: age> 55 years [HR10.51 (95%CI 1.12-95.9); p=0.037]; no long acting penicillin therapy [HR 18.1 (95% CI 2.6-122.9); p=0.003]; TNFα > 80 ng/ml [HR 5.85 (95% CI 1.1-31.42); p=0.039]; and TIMP-2 > 289 ng/ml [HR 0.52 (95% CI 0.22-0.95); p=0.045]. CONCLUSION: Chronic inflammation and ECM remodeling are involved in late mitral restenosis after PMC.

Oncostatin M was associated with thrombosis in patients with atrial fibrillation.

The mechanism underlying thrombosis in atrial fibrillation (AF) is not yet clearly understood. Oncostatin M (OSM), as a member of IL-6 family, is involved in atherosclerosis-mediated thrombosis. The present study hypothesizes that OSM and its downstream factors play a role in thrombogenesis in AF.The specimens of left atrial appendages collected from patients with rheumatic mitral stenosis who underwent valve replacement were divided into 3 groups: sinus rhythm, AF(+)/thrombus(-), and AF(+)/thrombus(+) group. The macrophage infiltration in atrial tissue was assessed by immunohistochemistry, and the amount of OSM, tissue factor (TF), and tissue factor pathway inhibitors (TFPIs) was detected by Western blot.The infiltration of the M1 macrophages was significantly increased in the AF with thrombus group compared with the sinus rhythm group (P = .03). Moreover, the expression of OSM and TF was much higher in the AF with thrombus group compared with the sinus rhythm group (P = .02, .009, respectively) while the TFPI was decreased in the AF with thrombus group (P = .04).OSM might be correlated with thrombosis in patients with AF mediated by TF and TFPI.

Correlation of tissue selectin expression and hemodynamic parameters in rheumatic mitral valve disease.

BACKGROUND AND AIM OF THE STUDY: The study aim was to examine tissue expression of the adhesion molecules E-selectin and P-selectin on atrial, valvular and atrial myocardial blood vessel endothelium in patients with rheumatic mitral stenosis, and to investigate whether such expression was correlated with hemodynamics. METHODS: Thirteen patients (eight women, five men; mean age 51 +/- 10 years) with severe rheumatic mitral stenosis who underwent mitral valve replacement surgery were examined on preoperative day 1, using cardiac catheterization and echocardiography. Specimens from the mitral valve and left atrium of each patient were evaluated for CD 62E and CD 62P expression using indirect immunoperoxidase and immunofluorescence techniques RESULTS: A great majority of patients presented E and/or P selectin expression of variable intensity on atrial, valvular and atrial myocardial blood vessel endothelium. A more diffuse and stronger reaction for CD 62P was noted compared to that for CD 62E. The left ventricular end-diastolic diameter and left atrial diameter were positively correlated with endocardial CD 62P and CD 62E expression. Right atrial pressure was also strongly and positively correlated with endocardial expression of CD 62E (r = 0.80, p 0.03) and CD 62P (r = 0.8, p = 0.02). CONCLUSION: Marked tissue expression of CD 62E and CD 62P was identified on atrial, valvular and atrial myocardial blood vessel endothelium. Moreover, the degree of expression of adhesion molecules was significantly correlated with the left atrial and left ventricular chamber diameters, as well as right atrial pressure.

[Vascular reactivity response to mental stress in pregnant women with mitral stenosis]. / Estudo da reatividade vascular induzida pelo estresse mental na gravidez de mulheres portadoras de estenose mitral.

OBJECTIVE: To study vascular reactivity according to the analysis of blood flow and peripheral vascular resistance at rest and during mental stress in pregnant women with mitral stenosis. METHODS: Twenty two women with mitral stenosis, 13 of whom were pregnant (PS) and 9 were non-pregnant (MIS), and 9 healthy pregnant women (NP) were studied. During gestation, 9 out of the 13 patients of the PS group required a beta-blocker (PSB) and the remaining 4 progressed without medication (PSWB). Plethysmography at rest and during mental stress analyzed muscle blood flow, peripheral vascular resistance (PVR), mean arterial pressure (MAP) and heart rate (HR) during gestation and puerperium. RESULTS: During gestation of PSWB, muscle blood flow and HR were higher in 1.6% and 20.5% (p = 0.05), and PVR and MAP were lower in 19.3% and 4.4%, respectively, in comparison to the puerperium; during mental stress, the muscle blood flow increased by 55.9%, HR decreased by 30.2% and PVR and MAP were similar. In PSB, muscle blood muscle blood flow and HR were greater in 5.9% and 14.9% (p= 0.001) and MAP and PVR were lower in 10.3% and 9.1%, respectively, when compared to the puerperium. During mental stress, muscle blood flow and MAP increased by 69.8% and 174.1%, respectively. HR was similar and PVR decreased by 53.7%. The comparative study showed that in the NP group the muscle blood flow was higher, PVR was lower, and MAP and HR were similar in relation to the PS group, and that the PS, NP, MIS groups had a similar response to mental stress. CONCLUSIONS: Vascular reactivity in pregnant women with mitral stenosis was preserved and the analysis of measurements showed lower values of muscle blood flow and higher values of PVR when compared to those of healthy pregnant women.

Effect of balloon mitral valvuloplasty on exercise capacity, ventilation and skeletal muscle oxygenation.

OBJECTIVES: The short- and long-term effects of valvuloplasty on exercise capacity, ventilation and skeletal muscle oxygenation were investigated to determine whether a dissociation between hemodynamic improvement and exercise capacity occurs in patients with mitral stenosis. BACKGROUND: Percutaneous balloon mitral valvuloplasty in patients with mitral stenosis results in immediate hemodynamic improvement at rest and with exercise. Improved exercise capacity has been described at 3 months after valvuloplasty. In patients with left ventricular dysfunction, acute therapeutic interventions that produce hemodynamic benefit do not immediately improve exercise capacity. METHODS: Maximal bicycle exercise with measurement of respiratory gases was performed in 11 patients with mitral stenosis before and at 48 h and 3 months after successful percutaneous balloon mitral valvuloplasty. Respiratory and leg skeletal muscle oxygenation were assessed by monitoring changes in light absorption of the serratus anterior and vastus lateralis muscles using near-infrared spectroscopy and were expressed as percent deoxygenation. RESULTS: Mitral valvuloplasty significantly increased mean mitral valve area from 1.0 +/- 0.2 to 1.7 +/- 0.3 cm2 (p < 0.05). Immediately after valvuloplasty, peak exercise oxygen consumption (VO2), VO2 at the anaerobic threshold, ventilation, peak respiratory and leg muscle deoxygenation all remained unchanged. At submaximal work loads, respiratory muscle deoxygenation was attenuated (25 W: before 12 +/- 4%; 48 h 4 +/- 3%; 50 W: before 10 +/- 5%; 48 h 5 +/- 4%; both p < 0.05). At 3 months, significant improvement in peak VO2 (before 10.9 +/- 5%; 3 months 14.6 +/- 6.2 ml/kg per min; p < 0.05) and VO2 at the anaerobic threshold (before 7.1 +/- 2.4; 3 months 8.4 +/- 2.3; p < 0.05) were observed, whereas ventilation remained unchanged. No further improvement was seen in respiratory muscle deoxygenation. Vastus lateralis deoxygenation at submaximal work loads tended to be decreased. CONCLUSIONS: Long-term changes in skeletal muscle and the lungs preclude immediate enhancement of exercise performance after balloon mitral valvuloplasty. Immediate symptomatic improvement probably results from an immediate decrease in the work of breathing. Long-term symptomatic improvement results from changes that occur in the peripheral skeletal musculature as well as from the reduced work of breathing.

Myocardial enzyme activities in patients with mitral regurgitation or mitral stenosis.

To determine the adaption of myocardial metabolism in mitral regurgitation and mitral stenosis, human papillary muscles obtained during open heart surgery were analysed to measure selective enzyme activities in energy metabolism. All enzyme activities were expressed per unit dry weight muscle, per unit alkali soluble protein, and per unit total creatine and the different results compared. The activities of enzymes concerned with mitochondrial energy production and energy transfer (namely, citrate synthase and mitochondrial creatine kinase) tended to be higher in papillary muscles from hearts with mitral regurgitation than in those with mitral stenosis. The activities of enzymes concerned with cytoplasmic energy production (creatine kinase MM, lactate dehydrogenase, and phosphofructokinase) did not show statistically significant differences between mitral regurgitation and mitral stenosis. The ratio of creatine kinase MB activity to total creatine content showed the greatest difference when papillary muscles from patients with mitral regurgitation and mitral stenosis were compared (31% higher in mitral regurgitation; p less than 0.001). The specific function of creatine kinase MB, which is located in cytoplasm, is not well defined. Creatine kinase MB activity increases with extreme endurance training of human skeletal muscle. Thus the higher creatine kinase MB activity in papillary muscle of mitral regurgitation may represent an adaptation to increased physical demand.