Coronary Restenosis ; metabolism ; Heart Valve Diseases ; Humans ; Osteopontin ; metabolism

BACKGROUND AND OBJECTIVES: To compare the pattern of myocardial fibrosis in various valvular heart diseases (VHD), the morphometric data of the myocardial tissue and serum biochemical markers of myocardial fibrosis were analyzed in patients with aortic stenosis (AS), aortic regurgitation (AR) and mitral regurgitation (MR). SUBJECTS AND METHODS: Blood samples were obtained from 21 patients with AS, 23 with AR and 29 with MR. The serum levels of aminoterminal propeptide, of type I/III procollagen (PINP/PIIINP), and fibronectin were measured to estimate the synthesis of the extracelluar matrix. The carboxy-terminal telopeptide collagen type I (CITP), matrix metalloproteinase-1 (MMP-1, collagenase) and the tissue inhibitor, metalloproteinase-1 (TIMP-1), were also measured to estimate the collagen degradation and metabolism activities. The left ventricular mass (LVM) was calculated by echocardiography. Of the patients, myocardial tissue was obtained during surgery in 11 with AS, 8 with AR and 13 with MR;the collagen volume fraction (CVF) was calculated using picrosirius red staining. RESULTS: The LVM was significantly larger in the AS and AR groups compared to the MR group (p<0.001), and the CVF also showed significant differences (13+/-3% in AS, 10+/-3% in AR, and 6+/-3% in MR, p<0.001). The fibronectin level was significantly elevated in the AS and AR groups than the MR group (p<0.001), whereas the CITP and MMP-1 levels were significantly higher in the MR group (p<0.05). The PINP/PIIINP showed no significant difference between the groups (p>0.05), and the biochemical markers were no different between the AS and AR groups (p>0.05). Fibronectin was the only parameter showing a positive correlation with both the CVF (r=0.388, p=0.01) and the left ventricular mass (r=0.278, p=0.02). CONCLUSION: Different mechanisms for the matrix synthesis and degradation were present for the maintenance of myocardial fibrosis and hypertrophy according to the type of VHD, and fibronectin, a major non-collagenous extracelluar matrix, was proved to be an important factor associated with cardiac hypertrophy and myocardial fibrosis.
Aortic Valve Insufficiency ; Aortic Valve Stenosis ; Biomarkers ; Cardiomegaly ; Collagen ; Collagen Type I ; Echocardiography ; Fibronectins ; Fibrosis* ; Heart Valve Diseases* ; Humans ; Hypertrophy ; Matrix Metalloproteinase 1 ; Metabolism ; Mitral Valve Insufficiency ; Procollagen

BACKGROUND AND OBJECTIVES: Left ventricle burdened by longstanding volume-overload, undergoes various structural and functional alterations. Accordingly, the expressions of multiple classes of genes are likely to be altered. However, the profile of gene expressions, specifically in a volume-overloaded left ventricle in humans, has not been explored. SUBJECTS AND METHODS: The pattern of gene expression was studied, using a cDNA microarray, in myocardium from 4 normal subjects and 5 patients with chronic regurgitant valvular heart disease whose end-diastolic left ventricular dimension measures 65 mm or more, but whose systolic function remained preserved. RESULTS: We identified 58 differentially expressed genes that were functionally classifiable in the volume-overloaded myocardium. Those genes involved in cell cycle/growth (up/down-regulation: 9/1), signal transduction (4/1) were mostly overexpressed in the volume-overloaded myocardium. The distributions of the gene expressions were variable for those involved in transcription/translation (up/down-regulation: 6/7) and apoptosis (2/2). The genes related to the myocyte structure (troponin T3, tropomyosin, etc)(up/down-regulation: 1/10), as well as those related to metabolism (2/5), were underexpressed. The gene expression patterns from RT-PCR and Western blot, with randomly selected genes, were similar to those from the cDNA microarray. CONCLUSION: Altered expression was identified in multiple genes in the volume-overloaded human left ventricle prior to the development of heart failure. The genes related to cell growth and signal transduction were mostly overexpressed, while those related to cellular structure and metabolism appeared to be underexpressed. These results might help in the elucidation of cellular mechanisms for the remodeling process associated with chronic volume-overloading.
Apoptosis ; Blotting, Western ; Cellular Structures ; Gene Expression* ; Heart Failure* ; Heart Valve Diseases ; Heart Ventricles ; Heart* ; Humans* ; Metabolism ; Muscle Cells ; Myocardium* ; Oligonucleotide Array Sequence Analysis ; Signal Transduction ; Transcriptome* ; Tropomyosin

OBJECTIVETo investigate whether valvular expression of macrophage and its subsets and correlative cytokines of mitral valve are altered in patients with rheumatic valvular disease.

METHODSThe mitral valvular leaflets of 15 rheumatic valvular disease patients were included as the test group, and 7 patients of terminal stage cardiomyopathy as the control. The immunostain of CD68, inducible nitric oxide synthase (iNOS) and CD163 were applied to mark the total macrophages, M1 and M2, respectively. The expression of endothelial nitric oxide synthase (eNOS), IL-10, Arg-1, macrophage-colony stimulating factor (M-CSF) were compared respectively in two groups.

RESULTSThe angiogenesis was enormous in the test, whereas the cell proliferation was scanty. Compared with the control, CD68 positive macrophages were markly expressed in the test (4.2 ± 2.0 vs. 3.2 ± 2.3; Z = -3.981, P = 0.000), also the iNOS positive M1 subsets (3.4 ± 1.7 vs. 1.2 ± 1.0; Z = -4.015, P = 0.000). The expression level of CD163 positive macrophages was lower in the test (1.2 ± 1.0 vs. 2.3 ± 1.8; Z = -8.602, P = 0.000). The expression of eNOS was higher in the rheumatic valve disease (4.9 ± 1.1 vs. 1.8 ± 1.1), but the expression levels of Arg-1 (1.0 ± 1.0 vs. 3.3 ± 1.3) and IL-10 (2.1 ± 1.2 vs. 4.9 ± 1.4) were lower (Z = -8.867 to -5.344, P = 0.000). The expression of M-CSF was lower in test (2.0 ± 1.4 vs. 4.3 ± 0.9; Z = -2.741, P = 0.006).

CONCLUSIONSThe infiltration of M1 macrophages plays an important role in the progression of rheumatic mitral valve disease. It fulfills the pro-inflammation by up-regulating the expression of eNOS. Inversely, it suppresses the expression of IL-10, Arg-1 to relieve the inflammatory action. In according with the down-regulated level of M-CSF, the polarization from M1 macrophages into M2 is depressed, and the inflammation induced by M1 is sustained.

Adult ; Aged ; Female ; Heart Valve Diseases ; pathology ; Humans ; Interleukin-10 ; metabolism ; Macrophage Colony-Stimulating Factor ; metabolism ; Macrophages ; metabolism ; Male ; Middle Aged ; Mitral Valve ; Nitric Oxide Synthase Type III ; metabolism ; Rheumatic Heart Disease ; pathology

OBJECTIVETo investigate if the increased incidence of atrial fibrillation with age was associated with changes of Na(+) channel in atrial myocytes.

METHODSTwenty-three patients underwent valve replacement operations were divided into adult [< 60 years, n = 15, 9 males, mean age (42.1 +/- 7.1) years] and aged group [> or = 60 years, n = 8, 5 males, mean age (63.3 +/- 3.1) years]. All patients were in normal sinus rhythm. Whole cell patch clamp techniques were used to record the Na(+) currents (I(Na)) of right auricle myocytes.

RESULTSBoth current density and time-dependent recovery of I(Na) were similar in the cells from the 2 groups. Voltage-dependent inactivation of I(Na) of myocytes in the aged atria was shifted to more positive voltages.

CONCLUSIONCurrent density of I(Na) was similar between the 2 age groups, and Na(+) channel might not be an important determinant for the increased incidence of atrial fibrillation in aged patients.

Adult ; Age Factors ; Atrial Fibrillation ; Female ; Heart Atria ; cytology ; physiopathology ; Heart Valve Diseases ; physiopathology ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Sodium Channels ; analysis

OBJECTIVE: To determine the mechanism of protective effect of noninvasive limb ischemic preconditioning (NIPC) on myocardium of patients with rheumatic heart disease undergoing heart valve surgery under cardiopulmonary bypass (CPB). METHODS: A total of 32 patients with rheumatic heart disease undergoing heart valve surgeries under CPB were randomly divided into 2 groups: a control group(n=16)and an NIPC group(n=16).Tourniguet was used for each patient in the NIPC group around both the upper extremities in turn, inflated for 8 min and deflated for 5 min for 3 cycles. After the anesthesia, the remaining procedures were the same as in the control group. Blood samples were collected from the central vein after the induction of anesthesia (T(1)), 5 min before aortic clamp (T(2)),30 min after aortic opening (T(3)), 6 h after the operation (T(4)), and 24 h after the operation (T(5)) to measure the concentration of cardiac troponin I and creatine kinase MB in the plasma and CGRP and ET-1 in the serum. Pathologic change of the right auricle of the heart tissue during the superior vena cave intubation and extubation was detected. RESULTS: The content of cardiac troponin I and creatine kinase MB at T(4) and T(5) in the 2 groups was higher than that of other time points in the same group, and it reached the peak at T(5). Comparison of the content of cardiac troponin I and creatine kinase MB at T(4) and T(5) in the 2 groups showed significant difference, and that of the NIPC group was lower than the control group(P<0.05).CGRP and ET-1 contents reached the peak at T(2) in the NIPC group and at T(3) in the control group, but the peak of CGRP in the NIPC group was higher than that in the control group(P<0.01).The peak of ET-1 content in the NIPC group was lower than that in the control group(P<0.01). After the CPB, myocardial and mitochondrion impairment was lighter in the NIPC group than in the control group. CONCLUSION Noninvasive limb ischemic preconditioning can protect the myocardium through increasing CGRP, inhibiting ET-1, and advancing the peak of CGRP and ET-1.
Adult ; Arm ; blood supply ; Calcitonin Gene-Related Peptide ; metabolism ; Cardiopulmonary Bypass ; Female ; Granulins ; Heart Valve Diseases ; surgery ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Ischemic Preconditioning ; methods ; Male ; Middle Aged ; Mitral Valve ; surgery ; Myocardial Reperfusion Injury ; prevention & control ; Rheumatic Heart Disease ; surgery

BACKGROUND/AIMS: Underlying cardiac pathology and atrial fibrillation (AF) affect the molecular remodeling of ion channels in the atria. Changes in the expression of these molecules have not been demonstrated in Korean patients with mitral valvular heart disease. Thus, the purpose of this study was to analyze ion channel expression in patients with chronic AF and mitral valvular heart disease. METHODS: A total of 17 patients (eight males and nine females; mean age, 57 +/- 14 years [range, 19 to 77]) undergoing open-heart surgery were included in the study. Twelve patients (seven with coronary artery disease and five with aortic valvular disease) had sinus rhythm, and five patients (all with mitral valvular disease) had chronic, permanent AF. A piece of right atrial appendage tissue (0.5 g) was obtained during surgery. RT-PCR was used to evaluate the expression of L-type Ca2+ channels, ryanodine receptor (RyR2), sarcoplasmic reticular Ca2+-ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier Ikr (HERG), gene encoding calcium-independent transient outward current I(to1) (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier Iku (Kv1.5), K+ channel-interacting protein 2 (KChIP2), hyperpolarization-activated cation channel 2 associated with the pacemaker current If (HCN2), and gene encoding Na+ channel (SCN5A). RESULTS: Reduced L-type Ca2+ channel, RyR2, SERCA2, Kv1.5, and KChIP2 expression and borderline increased HCN2 expression were observed in the patients with AF and mitral valvular heart disease. Left atrial diameter was negatively correlated with RyR2 and KChIP2 expression. Fractional area shortening of the left atrium was positively correlated with RyR2 and KChIP2 expression. CONCLUSIONS: Alterations in ion channel expression and the anatomical substrate may favor the initiation and maintenance of AF in patients with mitral valvular heart disease.
Adult ; Aged ; Aortic Valve Stenosis/metabolism ; Atrial Fibrillation/*metabolism ; Calcium/metabolism ; Chronic Disease ; Coronary Artery Disease/metabolism ; Female ; Heart Valve Diseases/*metabolism ; Humans ; Ion Channels/*genetics ; Male ; Middle Aged ; *Mitral Valve ; Potassium Channels/genetics ; Ryanodine Receptor Calcium Release Channel/genetics ; Sodium Channels/genetics

OBJECTIVETo investigate the brain protective effects of Ginkgo biloba leaf extract (Ginaton) in patients who underwent hypothermic cardiopulmonary bypass (CPB).

METHODSSixty patients with rheumatic heart disease of ASA grade II-III, who were scheduled for mitral valve replacement with intravenous anaesthesia, were randomly assigned to two groups, the Ginaton group (30 patients) treated with Ginaton 1 mg/kg by intravenous dripping before open heart for CPB, and the control group (30 patients) with normal saline instead. Blood was synchronously collected from arteriae radialis and vena jugularis interna at 5 time points, namely, before CPB (T1), nasopharyngeal temperature (lowered to 30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 after CPB (Ts) for determining blood gas, lactate acid concentration, activity of superoxide dismutase (SOD) and malonaldehyde (MDA) content. And the oxygen content in artery (CaO2) and jugular vein (CjvO2), the difference of oxygen contents in arterial and jugular vein (Ca-jvO2), the cerebral oxygen extraction ratio (ERO2) as well as the arteriojugular lactate difference (ADVL) were calculated.

RESULTSAfter the beginning of CPB, as compared with those in the control group, in the Ginaton group, the reduction of Ca-jvO2 and ERO2 was significantly higher (P < 0.05 or P < 0.01) and the increase of lactate acid, ADVL and MDA were significantly lower, and with a remarkably higher SOD activity (P < 0.01).

CONCLUSIONGinaton could improve cerebral oxygen supply, promote SOD activity to inhibit production of free radicals in patients undergoing CPB, and thus shows an evident protective effect in the brain.

Adult ; Brain ; blood supply ; drug effects ; metabolism ; Cardiopulmonary Bypass ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ginkgo biloba ; Heart Valve Diseases ; surgery ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Middle Aged ; Mitral Valve ; surgery ; Neuroprotective Agents ; therapeutic use ; Oxygen ; metabolism ; Phytotherapy ; Plant Extracts ; therapeutic use ; Plant Leaves ; chemistry ; Treatment Outcome

OBJECTIVETo investigate the association of serum chemerin with degenerative aortic valve disease (DAVD) in patients with metabolic syndrome.

METHODSFrom July, 2012 to July, 2013, 48 patients with metabolic syndrome (mean age 56.33∓6.14 years, including 25 male and 23 female patients), 48 patients with metabolic syndrome and DAVD (mean age 60.16∓6.72 years, 24 males and 21 females), and 48 adult healthy volunteers (mean age 52.94∓8.28 years, 23 males and 25 females) were examined for triglyceride, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein, fasting glucose, C-reactive protein and other biochemical indexes. Serum chemerin levels were detected using ELISA for all the subjects.

RESULTSPatients with metabolic syndrome had higher levels of serum chemerin than the healthy subjects, and patients with DAVD had higher chemerin levels than those with DAVD. Multivariate logistic regression analysis showed that increased serum chemerin level is a predictor of aortic valve degeneration in patients with metabolic syndrome. Univariate linear regression analysis showed that serum chemerin levels, body mass index, systolic blood pressure, total triglyceride and C-reactive protein were associated with metabolic syndrome. Stepwise multiple linear regression analysis identified correlations of body mass index and C-reactive protein with serum chemerin level.

CONCLUSIONElevated serum chemerin level can be a predictor for DAVD in patients with metabolic syndrome.

Adult ; Aged ; Aortic Valve ; Blood Pressure ; Body Mass Index ; C-Reactive Protein ; metabolism ; Chemokines ; blood ; Cholesterol, LDL ; blood ; Female ; Heart Defects, Congenital ; complications ; Heart Valve Diseases ; complications ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Lipoproteins, HDL ; blood ; Male ; Metabolic Syndrome ; blood ; complications ; Middle Aged ; Triglycerides ; blood