MI Group Research Articles

Pamidronate Attenuates Diastolic Dysfunction Induced by Myocardial Infarction Associated with Changes in Geometric Patterning

Background/Aims: The aim of this study was to evaluate the influence of pamidronate on ventricular remodeling after myocardial infarction. Methods: Male Wistar rats were assigned to four groups: a sham group, in which animals were submitted to simulated surgery and received weekly subcutaneous injection of saline (S group; n=14); a group in which animals received weekly subcutaneous injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated surgery (SP group, n=14); a myocardial infarction group, in which animals were submitted to coronary artery ligation and received weekly subcutaneous injection of saline (MI group, n=13); and a myocardial infarction group with pamidronate treatment (MIP group, n=14). The rats were observed for three months. Results: Animals submitted to MI had left chamber enlargement and worse diastolic and systolic function compared with SHAM groups. E/A ratio, LV posterior and relative wall thickness were lower in the MIP compared with the MI group. There was no interaction between pamidronate administration and MI on systolic function, myocyte hypertrophy, collagen content, and calcium handling proteins. Conclusion: Pamidronate attenuates diastolic dysfunction following MI.

Pharmacological Inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis in Mice Cardiac Fibroblast and Post-Myocardial-Infarction Models

Background: To investigate the role of focal adhesion kinase (FAK)-mediated signaling in hypoxia-induced cardiac fibroblasts (CFs) differentiation and cardiac fibrosis post-myocardial infarction (MI) on a mice model. Methods: CFs of neonatal C57BL/6 mice were treated under normoxic, hypoxic, or hypoxic+PP2 (known as a Src kinase family inhibitor) conditions. Gene expressions of FAK, alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1), or α-SMA and vimentin levels were performed by RT-PCR and immunofluorescence staining, respectively. Thirty mice were surgically treated into Sham (n=7) and MI (n=23) groups; and FAK inhibitor PF-562271 was given to six survivor MI mice (as PF group, from 15 survivors). Heart function and collagenous tissues were examined by echocardiography, as well as by Masson‘s trichrome and Sirius red staining, respectively. Type I collagen, FAK protein, mTOR, ERK1/2, AKT, P70S6K and phospho-FAK levels were also analyzed. Results: FAK inhibition with PP2 significantly decreased CFs differentiation and collagen synthesis under hypoxia treatment. In vivo, PF-562271 treatment resulted in fibrosis attenuation; however, deteriorated heart function of MI mice could not be significantly improved. PF-562271 may affect phospho-mTOR (p<0.05), phospho-ERK1/2 (p<0.01), phospho-AKT (p<0.001) and phospho-P70S6K (p<0.05) to exert its benefits. FAK can be activated either under hypoxia in CFs or MI in a mouse model to promote fibrosis. However, pharmacological inhibition of FAK can attenuate fibrosis response. Conclusion: This study provides novel evidence that FAK inhibition may become a promising pharmaceutical strategy to attenuate fibrosis post-MI.

Novel mouse model of left ventricular pressure overload and infarction causing predictable ventricular remodelling and progression to heart failure.

Mouse surgical models are important tools for evaluating mechanisms of human cardiac disease. The clinically relevant comorbidities of hypertension and ischaemia have not been explored in mice. We have developed a surgical approach that combines transverse aortic constriction and distal left anterior coronary ligation (MI) to produce a gradual and predictable progression of adverse left ventricular (LV) remodelling that leads to heart failure (HF). Mice received either sham, MI alone, transverse aortic constriction alone or HF surgery. Infarct size and LV remodelling were evaluated by serial 2-D echocardiograms. Transverse aortic constriction gradients were measured by the Doppler velocity-time integral ratio between constricted and proximal aortic velocities. At 4weeks, hearts were weighed and analysed for histology and brain natriuretic peptide, a molecular marker of HF. Echocardiographic analysis of segmental wall motion scores showed similarly small apical infarct sizes in the MI and HF groups at day1 postsurgery. MI alone showed little change in infarct size over 4weeks (0.26±0.02 to 0.27±0.04, P=0.77); however, HF mice showed infarct expansion (0.25±0.06 to 0.39±0.09, P<0.05). HF mice also showed LV remodelling with increases in LV volumes (1day=36.5±5.2mL, 28days=89.1±16.0mL) versus no significant changes in the other groups. Furthermore, systolic function progressively deteriorated in the HF group only (ejection fraction, 1day=55.6±3.6%, 28days= 17.6±4.1%, P<0.05) with an increase of brain natriuretic peptide by 3.5-fold. This surgical model of pressure overload in the setting of a small infarction causes progressive deterioration of cardiac structural and functional properties, and provides a clinically relevant tool to study adverse LV remodelling and heart failure.

Integrative analysis of high-throughput RNAi screen data identifies the FER and CRKL tyrosine kinases as new regulators of the mitogenic ERK-dependent pathways in transformed cells.

BackgroundCell proliferation is a hallmark of cancer and depends on complex signaling networks that are chiefly supported by protein kinase activities. Therapeutic strategies have been used to target specific kinases but new methods are required to identify combined targets and improve treatment. Here, we propose a small interfering RNA genetic screen and an integrative approach to identify kinase networks involved in the proliferation of cancer cells.ResultsThe functional siRNA screen of 714 kinases in HeLa cells identified 91 kinases implicated in the regulation of cell growth, most of them never being reported in previous whole-genome siRNA screens. Based on gene ontology annotations, we have further discriminated between two classes of kinases that, when suppressed, result in alterations of the mitotic index and provoke cell-cycle arrest. Extinguished kinases that lead to a low mitotic index mostly include kinases implicated in cytosolic signaling. In contrast, extinguished kinases that result in a high mitotic index mostly include kinases implicated in cell division. By mapping hit kinases in the PhosphPOINT phosphoprotein database, we generated scale-free networks consisting of 449 and 661 protein-protein interactions for kinases from low MI and high MI groups, respectively. Further analyses of the kinase interactomes revealed specific modules such as FER- and CRKL-containing modules that connect three members of the epidermal growth factor receptor (EGFR) family, suggesting a tight control of the mitogenic EGF-dependent pathway. Based on experimental studies, we confirm the involvement of these two kinases in the regulation of tumor cell growth.ConclusionBased on a combined approach of large kinome-wide siRNA screens and ontology annotations, our study identifies for the first time two kinase groups differentially implicated in the control of cell proliferation. We further demonstrate that integrative analysis of the kinase interactome provides key information which can be used to facilitate or optimize target design for new therapeutic strategies. The complete list of protein-protein interactions from the two functional kinase groups will provide a useful database for future investigations.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1169) contains supplementary material, which is available to authorized users.

Abstract 13037: Tenascin-c Modulates Inflammatory Response and Aggravate Ventricular Remodeling After Myocardial Infarction in Mice Model

Tenascin-C (TN-C), an extracellular matrix glycoprotein, transiently appeared in myocardial tissue after acute myocardial infarction (AMI). We have previously reported that AMI patients with higher serum TN-C levels had worse long-term prognosis, suggesting TN-C may play important roles during the development of ventricular remodeling. However, the biological function of TN-C in ventricular remodeling is not fully understood. In this study, using TN-C knock-out(KO) mice, we investigated the effects of TN-C on LV remodeling and the biological function of TN-C during the acute phase of inflammatory responses after myocardial infarction. The 8 to 10 weeks old male wild type (WT) and TN-C knock-out (KO) mice were divided into 4 groups of WT+Sham, KO+Sham, WT+MI and KO+MI. Mice 12 weeks post-MI, the survival rate of both WT+MI (48.3%,14 of 29 mice) and KO+MI (55.6%,15 of 27 mice) groups had no significant difference. However, TN-C KO group had the better cardiac function than WT had (LVEF, 19.02±6.31% vs 10.63±4.43%; p&lt;0.001). Interstitial fibrosis at border area was significantly increased in the WT +MI group to compare with that of KO+MI, whereas the extent of fibrosis in the remote area revealed no significant difference between the two groups. By RT-PCR analysis, WT+MI group showed significantly higher expression of atrial natriuretic peptide at the border including infarcted areas than that of KO+MI at chronic MI phase. At acute phase, fluorescence activated cell sorting analysis showed that ratio of CD45+, CD11b+, Ly6c high pro-inflammatory monocyte were significantly decreased, whereas CD45+, F4/80+, CD206+, anti-inflammatory M2 macrophage were significantly increased in KO+MI compared with WT+MI group 7 days after MI. RT-PCR analysis showed that the expression of IL-10, an anti-inflammatory cytokine, was significantly higher in KO+MI than WT+MI. These findings suggest, TN-C aggravates the deterioration of LV function due to MI partly by modulating inflammation at acute phase.

Abstract 12954: Impairment of the Compensatory Natriuretic Peptide Response to Myocardial Infarction in the Aged is Associated With Adverse Cardiorenal Repair and Heart Failure

Introduction: The incidence of post-myocardial infarction (MI) heart failure (HF) is increasing in the elderly. Studies have demonstrated that B-type natriuretic peptide (BNP) mediates critical cardiorenal compensatory and protective actions through guanylyl cyclase receptor A and cGMP activation. Such actions include natriuresis, diuresis and suppression of adverse cardiorenal remodelling. Hypothesis: While the mechanism of this increased risk may be multifactorial, we hypothesized that an impairment of the compensatory protective BNP/cGMP axis in both the aged kidney and heart contributes to post-MI HF. Methods: 20 month old Fischer rats were randomized into two groups: Sham-operated (S) and MI(produced by left coronary artery ligation). Cardiorenal structure and function were assessed at 4 weeks and included mean arterial pressure(MAP), LV EF, LV chamber dimension, proteinuria, sodium (Na) excretion and fibrosis by picrosirius red staining. Plasma BNP and cGMP levels were assessed by RIA. Data presented as mean±SE,*P&lt;0.05. Results: LV EF (S:78±2, MI:46±3 %*) was significantly reduced in aged MI rats, despite no difference in LV fibrosis in the remote region and no change in MAP compared to aged sham rats. Post-MI HF was evident and characterized by a significant reduction in Na excretion (S:0.20±0.03, MI:0.13±0.01 mEq/day*) as well as significant increases in LV dilatation (S:7.2±0.1, MI:8.3±0.2 mm*) and cardiac hypertrophy (S:2.78±0.06, MI:3.25±0.16 mg/g*) in aged MI rats. Notably, plasma BNP (S:9±1, MI:11±2 pg/ml) failed to increase and plasma cGMP (S:44±6, MI:27±3 mm*) was significantly reduced in the MI group. Importantly, MI in the aged rat resulted in a significant loss in total renal mass (S:2739±83, MI:2351±68 mg*), consistent with renal atrophy, while no changes in proteinuria or renal fibrosis were observed. Conclusions: Post-MI dysfunction of the protective BNP/cGMP axis in the aged rat was associated with various cardiorenal abnormalities including renal atrophy, which may contribute to the pathophysiology of HF. This pre-clinical model provides new insights into post-MI HF and may be used to examine therapeutic strategies using natriuretic peptides to protect the heart and kidney in the elderly post-MI population.

Evaluation of the accuracy of patient-specific cutting blocks for total knee arthroplasty: a meta-analysis

Because published studies on the accuracy achieved with patient-specific guides during total knee arthroplasty (TKA) contradict each other, this systematic review and meta-analysis sought to compare radiological TKA outcomes when patient-specific cutting blocks (PSCB) were used to the outcomes when standard manual instrumentation was used. The meta-analysis was implemented according to PRISMA Statement Criteria. The primary endpoint was the hip-knee-ankle (HKA) angle, which represents the leg's mechanical axis. The accuracy of component placement in the coronal and sagittal planes, and the accuracy of femoral component rotation were also compiled. After testing for publication bias and heterogeneity across studies, data were aggregated random-effects modeling when necessary. Fifteen articles were included: 916 total knee arthroplasty cases in the PSCB group and 998 in the MI group. The mechanical axis did not differ between the two groups (weighted mean difference 0.07°; 95 % CI, -0.5° to 0.65°; p = 0.8). Risk ratio analysis revealed no protective effect of using PSCB relative to the appearance of HKA angle outliers (RR = 0.88; 95 % CI, 0.68-1.13; p = 0.3). There was a trend towards a protective effect with PSCB for the risk of femoral component outliers, but the opposite was observed for the tibial component. The implantation procedure was stopped in 30 cases because the surgeon-authors found excessive discrepancies between the intra-operative observations and the pre-operative plan. This meta-analysis found no evidence that using patient-specific cutting blocks provides superior accuracy to using manual instrumentation during TKA.

Early-stage minimally invasive procedures decrease perihematomal endothelin-1 levels and improve neurological functioning in a rabbit model of intracerebral hemorrhage

Introduction:To determine the effects of minimally invasive surgery (MIS) at various stages after intracerebral hemorrhage (ICH) on perihematomal endothelin (ET)-1 levels and neurological functioning. Methods: Sixty rabbits were randomly distributed into a model control group (MC group, 30 rabbits) or a MIS group (MI group, 30 rabbits). An ICH model was established in all animals. In the MI group, ICH was evacuated by MIS at 6, 12, 18, 24, and 48 hours (six rabbits at each time point) after the ICH was established. The animals in the MC group underwent the same procedures for ICH evacuation, but with a sham operation without hematoma aspiration. All the animals were sacrificed 7 days after the ICH was established. Neurological deficit scores were determined, and the perihematomal brain tissue was removed to determine the ET-1 levels, blood–brain barrier (BBB) permeability, and brain water content (BWC).Results:The neurological deficit scores, perihematomal ET-1 levels, BBB permeability, and BWC all decreased significantly in the MI group compared to the MC group. Performing the MIS for evacuating the ICH at 6 hours resulted in the most remarkable decreases in these indices, followed by a significant difference observed at 12 hours within the MI subgroups.Conclusions:Performing MIS at 6–12 hours after ICH resulted in the most significant decreases in neurological deficit scores, ET-1 levels, BBB permeability, and brain edema. The optimal time window for performing MIS for ICH evacuation might be within 6–12 hours after hemorrhage.

Imaging of cardiac and renal perfusion in a rat model with 13N-NH 3 micro-PET.

Cardiac dysfunction leads to decreased organ perfusion. We aimed to measure cardiac and renal perfusion simultaneously with the use of (13)N-NH3-microPET in different rat models. Ten male Wistar rats underwent sham surgery (n=5) or permanent coronary artery ligation to induce myocardial infarction (MI, n=5). Eleven weeks later (13)N-NH3-microPET scan was performed to study the cardiac and renal perfusion. Cardiac perfusion was significantly reduced in MI group, directly correlated with ejection fraction and inversely correlated with MI size (r=0.89; p<0.001 and r=-0.86; p<0.001 respectively). Renal perfusion showed a notional 17% non-significant reduction in MI group when compared to sham (3.44±0.40 vs. 4.12±0.48ml/g/min). There was a trend towards greater reduction of perfusion in cortical than medullar region. Cortex perfusion was negatively correlated with histological changes. (13)N-NH3-microPET may be a potential tool for evaluation of cardiac and renal functional and perfusion changes in presence of cardiac dysfunction in rat models.

Effects of different doses and duration of iron supplementation on curing iron deficiency anemia: an experimental study.

Many controversies persist with respect to the dosage and therapeutic duration concerning iron deficiency anemia (IDA) treatment. To identify the most suitable cure, this study evaluated the effect of iron supplementation with different doses and for different time periods in rats with iron deficiency anemia. The rats were randomly divided into five groups [normal control (NC), low- iron diet control (LC), normal doses of iron group (NI), middle dose of iron group (MI), and high dose of iron group (HI)]. Each group was subdivided into two subgroups (2 and 4 weeks). The rats were maintained on low-iron diets and treated with oral iron dextran at different dosages. Finally, we investigated red blood cell parameters, iron absorption and metabolism, oxidative stress, and the antioxidant capacity. Our study indicated that through the administration of normal dose iron by gavage to IDA rats, the levels of the red blood cell parameters can be restored in only 2 weeks. In the HI group, iron absorption and transferrin receptor expressions were markedly reduced after 2 weeks. However, the iron content, ferritin and hepcidin expressions were notably increased, and the changes were more apparent after 4 weeks. With increasing doses of iron supplementation and durations of treatment, the liver malondialdehyde (MDA) content in the LC, MI, and HI groups was markedly increased, whereas the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were obviously reduced. This study demonstrated that the dose of iron treatment for IDA should be controlled in a safe range, and a reasonable duration is also critical for IDA therapeutics.

Abstract 37: The Positive Inotropic S100a1 Prevents Arrhythmogenic Sarcoplasmic Reticulum Ca2+ Leak And Ventricular Arrhythmias

S100A1 has emerged as a key factor in the control of cardiomyocyte (CM) contractile performance. Improved sarcoplasmic reticulum (SR) function with enhanced Ca2+ resequestration appears critical for its cAMP-independent inotropic effects but raises concerns about potential diastolic SR Ca2+ leakage that might trigger fatal arrhythmias. Thus, the goal of this study was to determine the impact of S100A1 on ryanodine receptor 2 (RyR2)-mediated SR Ca2+ leakage in vitro and in vivo. S100A1 association with the RyR2 was significantly diminished (-50%) in failing cardiomyocytes and hearts with S100A1 downregulation, as shown by co-immunofluorescence, co-immunoprecipitation and proximity ligation assay. Adenoviral-mediated S100A1 overexpression (3-4 fold vs. GFP-control) in quiescent NCs (normal CMs) and FCs (failing CMs) decreased SR Ca2+-frequency (-50 and −40% respectively) and protected from β-AR-triggered diastolic Ca2+-waves (-62 and −58% respectively) in electrically stimulated (2Hz) CMs as assessed by epifluorescent and confocal Ca2+ imaging. In multicellular rat engineered heart tissue (EHT), S100A1-overexpression (6-8 fold vs. GFP-control) protected from Ca2+-triggered after-contractions (ACs) (-50%) with preserved enhancement of isometric twitch force (TF, +40%) at 2Hz. S100A1-mediated rescue of contractile failure of endothelin-1-treated EHT (-50% decrease in TF) was associated with protection from Ca2+-triggered ACs. In mice with post-ischemic heart failure, AAV9-mediated therapeutic administration of S100A1 enhanced S100A1/RyR2 association and prevented epinephrine-induced VTs (70% in MI group vs. 30% in MI-S100A1 group). Mechanistically, S100A1-overexpression changed neither PKA/CaMKII RyR2 phosphorylation pattern nor binding of accessory proteins like FKBP12.6, calmodulin or sorcin to RyR2 but enhanced S100A1/RyR2 stoichiometry. Our data provide evidence that S100A1 interaction with the RyR2 can beneficially modulate and reverse diastolic RyR2 function dysfunction. S100A1 appears to convey a rather unique molecular profile combining cAMP-independent inotropy with protection against Ca2+-triggered arrhythmias.

Conversion in mini-invasive colorectal surgery: The effect of timing on short term outcome

IntroductionDifferent results have been reported about postoperative outcomes of conversion during laparoscopic colorectal surgery.We aimed to detect the effect of conversion on postoperative outcome and to identify features associated to better outcome after conversion. MethodsTwo hundred-fourteen mini-invasive left colonic and rectal resections were retrospectively analysed.Two groups were identified: mini-invasive colorectal surgery (MI) that includes both laparoscopic and robotic resections, and conversion to open surgery. ResultsAmong 214 colorectal procedures, 189 were MI. Conversion rate was 11.7%. Operating time was shorter for MI at overall analysis (p 0.003) and sub-analysis of left colectomies (p 0.001). MI procedures had shorter hospital stay (p 0.000) both in left colectomy and rectal resection (p 0.008 and p 0.001 respectively).A shorter time to first flatus emission was detected in MI group in both overall analysis (p 0.003) and procedure's sub-analysis (left colectomy p 0.032; anterior rectal resection p 0.040).Oral feeding was resumed earlier after mini-invasive rectal resections (p 0.014).Converted procedures required more blood transfusions (p 0.000) and grade II complication rate was lower after MI procedures (p 0.013).Conversion presented higher anastomotic leakage and reoperation rates (p 0.035 and p 0.006 respectively). Conversion before 105 min (early conversion) had a significant lower number of blood transfusions (p 0.047). ConclusionsConversion is associated to higher rate of blood transfusions, grade II complication and slower recovery. Earlier conversion has better outcomes. Colorectal surgeons should identify any critical aspects that could avoid late conversion allowing reducing negative effects of conversion.

Minimally invasive versus open transforaminal lumbar interbody fusion: comparison of clinical outcomes among obese patients.

Minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) has been demonstrated in previous studies to offer improvement in pain and function comparable to those provided by the open surgical approach. However, comparative studies in the obese population are scarce, and it is possible that obese patients may respond differently to these two approaches. In this study, the authors compared the clinical benefit of open and MI TLIF in obese patients. The authors conducted a retrospective cohort study based on review of electronic medical records at a single institution. Eligible patients had a body mass index (BMI) ≥ 30 kg/m(2), were ≥ 18 years of age, underwent single-level TLIF between 2007 and 2011, and outcome was assessed at a minimum 6 months postoperatively. The authors categorized patients according to surgical approach (open vs MI TLIF). Outcome measures included postoperative improvement in visual analog scale (VAS), Oswestry Disability Index (ODI), estimated blood loss (EBL), and hospital length of stay (LOS). A total 74 patients (21 open and 53 MI TLIF) were studied. Groups had similar baseline characteristics. The median BMI was 34.4 kg/m(2) (interquartile range 31.6-37.5 kg/m(2)). The mean follow-up time was 30 months (range 6.5-77 months). The mean improvement in VAS score was 2.8 (95% CI 1.9-3.8) for the open group (n = 21) and 2.4 (95% CI 1.8-3.1) for the MI group (n = 53), which did not significantly differ (unadjusted, p = 0.49; adjusted, p = 0.51). The mean improvement in ODI scores was 13 (95% CI 3-23) for the open group (n = 14) and 15 (95% CI 8-22) for the MI group (n = 45), with no significant difference according to approach (unadjusted, p = 0.82; adjusted, p = 0.68). After stratifying by BMI (< 35 kg/m(2) and ≥ 35 kg/m(2)), there was still no difference in either VAS or ODI improvement between the approaches (both unadjusted and adjusted, p > 0.05). Complications and EBL were greater for the open group than for the MI group (p < 0.05). Obese patients experienced clinically and statistically significant improvement in both pain and function after undergoing either open or MI TLIF. Patients achieved similar clinical benefit whether they underwent an open or MI approach. However, patients in the MI group experienced significantly decreased operative blood loss and complications than their counterparts in the open group.

Effects of minimally invasive procedures for evacuation of intracerebral hematoma in early stages on MMP-9 and BBB permeability in rabbits.

BackgroundThe effects of performing a minimally invasive procedure at different stages after intracerebral hemorrhage on perihematomal MMP-9 expression and blood–brain barrier (BBB) permeability were evaluated.MethodsSixty rabbits were randomly distributed into a model control group (MC group, 30 rabbits) or a minimally invasive group (MI group, 30 rabbits). A model of intracerebral hemorrhage was established in the MC and MI group. In the MI group, the intracerebral hematoma was evacuated by stereotactic minimally invasive procedures over 6 hours (6 rabbits), 12 hours (6 rabbits), 18 hours (6 rabbits) 24 hours or 48 hours (6 rabbits) following successful induction of intracerebral hemorrhage. The same procedure was performed in the MC group at the same time point but without evacuating the hematoma. All the animals were sacrificed within two weeks after the hematoma was surgically evacuated. A neurological deficit score was determined, and the perihematomal MMP-9 level and the BBB permeability were measured.ResultsThe neurological deficit score, perihematomal MMP-9 level and BBB permeability of the MI group decreased significantly compared to the MC group. Performing the MI procedure 6–12 h after intracerebral hemorrhage showed the most favorable outcome.ConclusionsRegarding the pathophysiological changes surrounding the hematoma, the optimal time window of performing MI procedures for the intracerebral hematoma evacuation might be within 6–12 h after hemorrhage.

Increased type VI collagen gene expression in the post‐MI human myocardium (1152.11)

Cardiac fibroblasts and myofibroblasts are responsible for post‐myocardial infarction (MI) remodeling via regulation of extracellular matrix (ECM) formation. Accelerated post‐MI remodeling leads to excessive ECM deposition and fibrosis which can contribute to impaired contractile function, arrhythmias, and heart failure. Type VI collagen has been shown to induce myofibroblast differentiation in cultured cardiac fibroblasts and could contribute to accelerated post‐MI remodeling. Type VI collagen is elevated in the myocardium 7 days, 14 days, and 20 weeks post‐MI in the rat. The absence of type VI collagen improved cardiac function post‐MI in a knock out mouse model. The purpose of this study was to determine if collagen VI gene expression was elevated in human myocardium post‐MI. Autopsy samples were obtained from subjects who had died within seven days of an MI (acute MI group) and subjects who had died of a non‐heart related issue with no documented prior MI (control group). Quantitative real time PCR reactions were performed with RNaseP as a reference gene for normalization. Type VI collagen gene expression in the acute MI group was 414% greater than the control group expression, but did not reach statistical significance in this small study. However, this preliminary data indicate that type VI collagen gene expression may be significantly elevated in the post‐MI human myocardium and warrants further study.Grant Funding Source: Supported by Shenandoah University School of Pharmacy Professional Practice Plan

Medium-term evaluation of internal fixation with pedicle screws for thoracolumbar fractures under minimally invasive endoscopy

Objective To evaluate the medium-term efficacy of internal fixation with pedicle screws under minimally invasive endoscopy for thoracolumbar fractures in comparison with traditional open pedicle screw fixation.Methods Included in this study were 96 patients who had been hospitalized for thoracolumbar fractures between January 2003 and December 2008 in our department.Of them,49 were treated with minimally invasive endoscopy (MI group) and 47 cases with traditional open pedicle screw fixation (open group).There were no significant differences between the 2 groups in general data (P ＞ O.05).The 2 groups were compared in terms of perioperative index,postoperative radiological data,visual analogue scale (VAS),Oswestry disability index (ODI) and systemic health condition.Results These patients were followed up for an average of 4.8 years.Compared with the open group,the MI group had significantly less perioperative bleeding,smaller incision,less postoperative drainage,shorter time for pain relief at the back and chest,shorter hospitalization,and shorter time for ambulatory recovery (P ＜ 0.05).There were no significant differences between the 2 groups in vertebral height,intervertebral disc height or kyphotic angle (P ＞ 0.05).The MI group scored significantly better in VAS and SF-36 than the open group postoperation (P ＜ O.05).There was no significant between-group difference in ODI (P ＞ 0.05).Conclusions In treatment of thoracolumbar fractures,minimally invasive endoscopy used for internal fixation with pedicle screws can lead to limited invasion,less pain and quick recovery.As far as the medium-term outcomes are concerned,it scores significantly better in evaluations of SF-36 score,systemic health condition,physical pain and physiological function than traditional open pedicle screw fixation. Key words: Spinal fractures; Fracture fixation, internal; Surgical procedures, minimally invasive; Endoscopy

Effects of urinary incontinence subtypes on women's quality of life (including sexual life) and psychosocial state

ObjectiveOur aim was to investigate the effects of urinary incontinence subtypes on women's quality of life (including sexual life) and psychosocial state. Study designThe patients, who applied to our clinic from March 2011 to August 2011, were identified and stratified into three groups: those with stress incontinence proved urodynamically (USI), those with urge incontinence (UI), and those with mixed incontinence urge incontinence (UI) proved by urodynamic and clinic evaluation. Scores on the Beck anxiety inventory (BAI), pelvic organ prolapse/urinary incontinence sexual questionnaire (PISQ-12), urogenital distress inventory (UDI-6), and incontinence impact questionnaire (IIQ-7) were compared between the urinary incontinence subtypes. ResultsAccording to urodynamic and clinical examination of 111 women with urinary incontinence, 59 (53%) had USI, 35 (32%) had UI, and 17 (15%) had MI. BAI-scores significantly differed between the USI and UI groups (p=0.030) and between the USI and MI groups (p=0.011) not between the UI and MI groups (p=0.597). UDI-6 scores did not significantly differ between the three groups (p=0.845). IIQ-7 scores significantly differed between the USI and MI groups (p=0.003) and between the UI and MI groups (p=0.006) but not between the USI and UI groups. Patients with USI had significantly lower PISQ-12 scores than those with UI (p=0.015). ConclusionsThese differences in the effects of incontinence subtypes should be kept in mind in the evaluation of patients with urinary incontinence. Psychiatric assessment may improve the management of incontinence in women, especially UI and MI.

Effects of renal denervation on the development of post-myocardial infarction heart failure and cardiac autonomic nervous system in rats

Prior studies indicated that radiofrequency renal denervation (RD)had beneficial effects on post-myocardial infarction (MI) heart failure(HF) in rats[1–3]. In this studywe aimedtoassessits effects on cardiacautonomic nervous system (CANS) which might be one of the mostimportant mechanisms of RD's therapeutic effect on post-MI HF anddetermine the best timing for RD.One hundred Wistar rats were randomly assigned intofiveexperimental groups: MI group (n = 20), RD group (n = 20),MI-1d + RD group (RD performed one day post-MI, n = 20),MI-4w + RD group (RD performed four weeks post-MI, n = 20),andNgroup(controlgroup, n = 20).MIwasproducedthroughligationof the anterior descending artery. RD was performed through strippingof the renal nerves. The experimental design and implementation wereconducted in accordance with animal welfare guidelines.Eight weeks post-MI, significant improvements were observed inboth MI-1d + RD and MI-4w + RD groups compared to the MIgroup, that include (1) improved left ventricular (LV) function andhemodynamics with increased water and sodium excretion;(2) decreased plasma and renal tissue norepinephrine levelswhile tissue norepinephrine content increased in myocardium;(3) increased β1-receptor in myocardium and improved heartratevariability;and(4)decreasedplasmarenin,angiotensinII,aldoste-rone,BNPandendothelinlevels.Moretherapeuticeffectswerefoundinthe MI-1d + RD group than the MI-4w + RD group (see Table 1 andFig. 1).Firstly, our study showed that RD attenuated the remodeling ofCANS and modulated its activities. RD leads to preservation of β1receptors content along with the β1 mRNA expression in non-infarcted cardiac tissue in this HF model (Fig. 1). This correlated withan improvement in heart function and cardiac remodeling. HRV is asensitive marker for the CANS [4]. RD led to a slower HR and higherSDNN in both intervention groups (See Table 1). The increase in SDNNindicates that cardiac sympathetic over-activation was suppressed andvagal activity was enhanced with the result of stabilizing cardiacelectrical activity, decreasing malignant arrhythmias, thereby reducingthe incidence of sudden death.Secondly, we found that RD blocked both peripheral and centralRAAS and sympathetic nervous system (SNS) at the same time. Andthis may answer the question how RD exerted effect on CANS. In ourstudy RD restores renin, angiotensin II, and aldosterone to near-normal levels. This not only explains the increase in sodium and waterexcretion, but also confirms that RD blocks renal RAAS via blockage ofthe efferent renal sympathetic nerves which is consistent with ourprevious study [2]. Studies have shown that angiotensin II not onlyactivates the central and peripheral SNS, function as part of a positivefeedback cycle between RAAS and the SNS, but also activates the localRAAS of other organs, notably the heart [5]. Our study also showedthat the plasma NE level in MI-1d + RD and MI-4w + RD groupsdecreased significantly, which reflects an overall reduction ofsympathetic activity, and especially represents reduction of centralsympathetic activity. This result maybe in part due to blockade of therenal sympathetic afferent pathway by RD. Furthermore, previousstudies have shown that during HF, the tissue NE levels of both theheart and kidney are decreased due to depletion, decreased reuptakeand increased spillover. The decrease of the tissue NE level causedfeedback activation of the central sympathetic system [6].Thus,increased tissue NE level may alleviate the activation of the centralsympathetic system, which was reflected by our data (Fig. 1).Many studies have shown that central RAAS stimulates the central

17 Cardiomyocytes Influence Fibroblast Proliferation and α-Smooth Muscle Actin Expression via the Secretion of Paracrine Mediators

IntroductionCardiac fibroblasts are known to modulate cardiomyocyte structure and function through soluble mediators. While less studied, the ability of cardiomyocytes to influence fibroblast properties, such as proliferation and activation, is...

Effects of doxycycline on cx43 distribution and cardiac arrhythmia susceptibility of rats after myocardial infarction.

This study aims to observe the effects of doxycycline (DOX) on gap junction remodeling after MI and the susceptibility of rats to cardiac arrhythmia. The proximal left anterior descending coronary artery of rats was ligated to establish a myocardial infarction animal model. DOX, methylprednisolone (MP), or vehicle was intraperitoneally injected into the animals for two weeks. Then, the heart size and heart function of all animals were determined through echocardiography. The experimental animals were sacrificed after the electrophysiologic study. Myocardial tissues were sampled to analyze the distribution of Cx43 using immunofluorescence; the Cx43 content was analyzed using western blot analysis; and the MMP-2 and MMP-9 activity in the myocardium was analyzed using gelatin zymography. The distribution of Cx43 in the border of the infarcted myocardia in the MI and MP groups was clearly disrupted and the Cx43 content was significantly reduced. In addition, the distribution of Cx43 in the border of the infarct in the DOX group was relatively regular, whereas two weeks of DOX treatment significantly inhibited MMP activity. Meanwhile, the induction rate of arrhythmia in the rats after DOX treatment was lower than those in the MI and MP groups. The results show that DOX treatment after myocardial infarction improves gap junction remodeling in the myocardial tissue near the infarcted area by inhibiting MMP activity and reducing susceptibility to cardiac arrhythmia.