Cannabinoid Receptor Agonist WIN55, 212-2 Attenuates Injury in the Hippocampus of Rats after Deep Hypothermic Circulatory Arrest.

OBJECTIVES: Postoperative neurological deficits remain a challenge in cardiac surgery employing deep hypothermic circulatory arrest (DHCA). This study aimed to investigate the effect of WIN55, 212-2, a cannabinoid agonist, on brain injury in a rat model of DHCA. METHODS: Twenty-four male Sprague Dawley rats were randomly divided into three groups: a control group (which underwent cardiopulmonary bypass (CPB) only), a DHCA group (CPB with DHCA), and a WIN group (WIN55, 212-2 pretreatment before CPB with DHCA). Histopathological changes in the brain were evaluated by hematoxylin-eosin staining. Plasma levels of superoxide dismutase (SOD) and proinflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-a) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression of SOD in the hippocampus was detected by Western blot and immunofluorescence staining. Levels of apoptotic-related protein caspase-3 and type 1 cannabinoid receptor (CB1R) in the hippocampus were evaluated by Western blot. RESULTS: WIN55, 212-2 administration attenuated histopathological injury of the hippocampus in rats undergoing DHCA, associated with lowered levels of IL-1ß, IL-6, and TNF-α (p < 0.05, p < 0.001, and p < 0.01, vs. DHCA, respectively) and an increased level of SOD (p < 0.05 vs. DHCA). WIN55, 212-2 treatment also increased the content of SOD in the hippocampus. The protein expression of caspase-3 was downregulated and the expression of CB1R was upregulated in the hippocampus by WIN55, 212-2. CONCLUSIONS: the administration of WIN55, 212-2 alleviates hippocampal injury induced by DHCA in rats by regulating intrinsic inflammatory and oxidative stress responses through a CB1R-dependent mechanism.

Risk factors for development of acute renal failure in 5077 coronary artery bypass grafting patients in the current era.

BACKGROUND: Acute renal failure (ARF) is one of the major complications after coronary artery bypass grafting (CABG) surgery. The risk factors are changing along with the technical evolution. The aim of this study was to identify the risk factors for ARF requiring dialysis after CABG surgery in the current era. METHODS: Between April 2012 and November 2019, 5077 consecutive patients who underwent CABG were analyzed retrospectively. The patients were divided into ARF group and non-ARF group according to whether ARF occurred and dialysis was required after operation. Univariate analysis was performed to find possible factors associated with ARF. Any variables that had trends to be associated with ARF were included in stepwise multiple logistic regression analysis. RESULTS: Of the 5077 patients who underwent CABG, 53 (1.04%) developed ARF requiring dialysis whereas 5024 (98.96%) were in non-ARF group. Cardiopulmonary bypass (CPB) time (odds ratio [OR], 1.009; 95% confidence interval [CI], 1.003-1.016; p = .006), insertion of intra-aortic balloon pump (IABP; OR, 19.294; 95% CI, 5.49-67.808; p = .000), and low ejection fraction (EF; OR, 0.943; 95% CI, 0.894-0.994; p = .030) were independent risk factors for development of ARF requiring dialysis in patients undergoing CABG surgery. CONCLUSION: Our study identified prolonged CPB time, insertion of IABP, and low EF as independent risk factors for developing ARF requiring dialysis after CABG. The results suggest that shortening of CPB time and protection of cardiac function are important factors to prevent ARF and that special care should be taken to protect the renal function when the patient need insertion of IABP.

Effect of CPB glucose levels on inflammatory response after pediatric cardiac surgery.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a common complication after cardiac surgery. There are no definite optimal glycemic threshold for pediatric patients receiving open-heart surgery with CPB. The study aimed to investigate the optimal cardiopulmonary bypass (CPB) glucose in patients undergoing cardiac surgery. METHODS: We enrolled children with congenital heart disease who underwent surgical repair between June 2012 and December 2020. We included only patients who underwent cardiac surgery with CPB. The primary outcome was severe SIRS. A two-piece-wise regression model was applied to examine threshold effect of CPB glucose on severe SIRS. RESULTS: A total of 7350 patients were enrolled in the present study, of whom 3895 (52.99%) are female. After potential confounders were adjusted, non-linear relationship was detected between CPB glucose and severe SIRS, whose turning point was 8.1. With CPB glucose < 8.1 mmol/L, the estimated dose-response curve was consistent with a horizontal line. However, the prevalence of severe SIRS increased with increasing glucose up to the turning point (Glucose > 8.1 mmol/L); the odds ratio (OR) of the Glucose was 1.35 (95% CI 1.21, 1.50). CONCLUSIONS: The present study indicates the association of CPB glucose with inflammatory response after pediatric cardiac surgery. The patients might have the best outcomes with the optimal CPB glucose no more than 8.1 mmol/L.

Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study.

BACKGROUND: Mitral valve disease (MVD)-associated atrial fibrillation (AF) is one of the most common arrhythmias with an increased risk of thromboembolic events. This study aimed to identify the molecular mechanisms and possible biomarkers for chronic AF in MVD by using multi-omics methods. METHODS: This prospective study enrolled patients with MVD (n=100) undergoing mitral valve replacement surgery. The patients were allocated into chronic AF and sinus rhythm (SR) groups. Plasma samples were collected preoperatively. Proteomics was performed with isobaric tags for relative and absolute quantitation (iTRAQ) to identify differential proteins (DPs) between the two groups. The selected DPs were then validated in a new cohort of patients by enzyme-linked immunosorbent assay (ELISA). A gas chromatography-mass spectrometer was used in the metabolomics study to identify differential metabolites (DMs). Bioinformatics analyses were performed to analyze the results. RESULTS: Among the 447 plasma proteins and 322 metabolites detected, 57 proteins and 55 metabolites, including apolipoprotein A-I (ApoA-I), apolipoprotein A-II (ApoA-II), LIM domain only protein 7 (LMO7), and vitronectin (VN) were differentially expressed between AF and SR patients. Bioinformatics analyses identified enriched pathways related to AF, including peroxisome proliferator-activated receptor alpha (PPARα), the renin angiotensin aldosterone system (RAAS), galactose, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. CONCLUSIONS: Using integrated multi-omics technologies in MVD-associated AF patients, the present study, for the first time, revealed important signaling pathways, such as PPARα, as well as possible roles of other signaling pathways, including the RAAS and galactose metabolism to understand the molecular mechanism of MVD-associated AF. It also identified a large number of DPs and DMs. Some identified proteins and metabolites, such as ApoA-I, ApoA-II, LMO7, and VN, may be further developed as biomarkers for MVD-associated AF.

Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest.

Neurological dysfunction commonly occurs after cardiac surgery with deep hypothermic circulatory arrest (DHCA). The mechanisms underlying DHCA-associated brain injury remain poorly understood. This study determined the changes in expression profiles of circular RNAs (circRNAs) in the hippocampus in rats that underwent DHCA, with an attempt to explore the potential role of circRNAs in the brain injury associated with DHCA. Adult male Sprague Dawley rats were subjected to cardiopulmonary bypass with DHCA. Brain injury was evaluated by neurological severity scores and histological as well as transmission electron microscope examinations. The expression profiles of circRNAs in the hippocampal tissues were screened by microarray. Quantitative real-time PCR (RT-qPCR) was used to validate the reliability of the microarray results. Bioinformatic algorithms were applied to construct a competing endogenous RNA (ceRNA) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential biological roles of the circRNAs. Out of 14 145 circRNAs screened, 56 were differentially expressed in the hippocampus between the DHCA and sham-operated rats, including 30 upregulated and 26 downregulated circRNAs. The expression changes of six selected circRNAs (upregulated: rno_circRNA_011190, rno_circRNA_012988, rno_circRNA_000544; downregulated: rno_circRNA_010393, rno_circRNA_012043, rno_circRNA_015149) were further confirmed by RT-qPCR. Bioinformatics analysis showed the enrichment of these confirmed circRNAs and their potential target mRNAs in several KEGG pathways including histidine metabolism, adipocytokine signaling, and cAMP signaling. By revealing the change expression profiles of circRNAs in the brain after DHCA, this study indicates possible involvements of these dysregulated circRNAs in brain injury and suggests a potential of targeting circRNAs for prevention and treatment of neurological dysfunction associated with DHCA.

Preoperative plasma biomarkers associated with atrial fibrillation after coronary artery bypass surgery.

OBJECTIVES: Postoperative atrial fibrillation (POAF) is a common complication in coronary artery bypass grafting (CABG) procedures. This prospective study aimed to investigate predisposition of proteins and metabolites correlated to POAF after CABG and related cellular pathways. METHODS: Preoperative plasma samples from patients undergoing CABG procedures were prospectively collected. After CABG, the patients were grouped to POAF or sinus rhythm (N = 170; n = 90 in the discovery set and n = 80 in the validation set). The plasma samples were analyzed using proteomics, metabolomics, and bioinformatics to identify the differential proteins and differential metabolites. The correlation between differential proteins and POAF was also investigated by multivariable regression analysis and receiver operator characteristic analysis. RESULTS: In the POAF(+) group, 29 differential proteins and 61 differential metabolites were identified compared with the POAF(-) group. The analysis of integrated omics revealed that preoperative alteration of peroxisome proliferators-activated receptor α and glutathione metabolism pathways increased the susceptibility of POAF after CABG. There was a correlation between plasma levels of apolipoprotein-C3, phospholipid transfer protein, glutathione peroxidase 3, cholesteryl ester transfer protein, and POAF. CONCLUSIONS: The present study for first time at multi-omics levels explored the mechanism of POAF and validated the results in a new cohort of patients, suggesting preexisting differential proteins and differential metabolites in the plasma of patients prone to POAF after CABG. Dysregulation of peroxisome proliferators-activated receptor α and glutathione metabolism pathways related to metabolic remodeling and redox imbalance-associated electrical remodeling may play a key role in the pathogenesis of POAF. Lower plasma phospholipid transfer protein, apolipoprotein-C3, higher cholesteryl ester transfer protein and glutathione peroxidase 3 levels are linked with POAF. These proteins/metabolites may be developed as biomarkers to predict POAF.

Corrective surgery alters plasma protein profiling in congenital heart diseases and clinical perspectives.

The final goal for treatment of congenital heart diseases (CHD) is to resume not only the normal heart structure but also physiology. The present study evaluates surgical results at molecular basis on the proteomic pattern in the pre- and post-operative period in tetralogy of Fallot (TOF) and ventricular septal defect (VSD) in order to find whether structure repair is associated with clinically important molecular changes in CHD. Differential protein analysis by using two-dimensional gel electrophoresis and mass spectrometry followed by ELISA validation was performed in the plasma samples of patients with TOF (n=82) or VSD (n=82) preoperatively, 6-month postoperatively, and in normal controls (n=82). A total of 473 protein spots in preoperative patients and 515 in postoperative patients were detected. Significantly (P<0.01) downregulated or upregulated proteins were detected. Validation of proteins in the new cohort of patients demonstrated that in VSD patients, postoperative complement component C3c (P<0.05) was partially and serum amyloid P-component (P<0.05) was completely recovered. In TOF patients, postoperative gelsolin (P<0.05) was partially recovered. In contrast, the elevated fibrinogen gamma chain level (P<0.01) in preoperative patients became normal postoperatively (P=0.1 vs. control). Thus, we have for the first time by using proteomic methods demonstrated that repair surgery for CHD not only corrects the structure malformation but also resumes the normality of certain altered proteins at molecular level. Identification of the recovered or unchanged proteins may facilitate the evaluation of the surgical results and the personalized management in postoperative period and long-term.

Loop isolation-based uploading preconditioning to protect heart from damage: a proof-of-concept study.

BACKGROUND: Little is known on the role of indirect clamp releasing in coronary artery bypass grafting (CABG). Loop isolation-based uploading preconditioning (LiuPhD) was modified to protect the heart from damage and the question of whether this can attenuate reperfusion injury after global myocardial ischemia was examined. METHODS: A post-hoc comparative analysis was conducted of a prospective single-arm trial on the use of the LiuPhD strategy for 60 multivessel-disease patients undergoing isolated first-time elective on-pump CABG versus 1:1 propensity score-matched patients from the historical database of the same center. RESULTS: A total of 120 matched patients had a median age of 62.0 (interquartile range [IQR] 55.8-69.0) years, 27 (22.5%) women, 35 (29.2%) with left main disease, and median follow-up of 18.5 (10.9-35.4) months. The LiuPhD group had shorter post-bypass times than conventional controls (10 [6-13] vs 14 [10-19] mins; p = 0.003). The LiuPhD group had similar needs in terms of composite cardiac-specific interventions (38/60 vs 44/60; p = 0.29). At follow-up of safety, the risk for composite major adverse cardiac and cerebrovascular events was similar between groups (event-free survival: 82.3% vs 73.8%; hazard ratio 1.00 [0.39, 2.54], p log-rank test = 0.99). CONCLUSION: The LiuPhD strategy is associated with short post-bypass times, comparable risk of myocardial injury, and similar safety compared with conventional direct clamp releasing.

Surgical Preparation Reduces Hydrogen Sulfide Released from Human Saphenous Veins in Coronary Artery Bypass Grafting.

The long-term patency rate of saphenous vein (SV) grafts is poor compared to arterial grafts. To investigate the effects of surgical preparation (distention) of SV on hydrogen sulfide (H2S) released from the endothelium, human SV segments were harvested from 43 patients during coronary artery bypass surgery (CABG). Acetylcholine (ACh) induced relaxation that was inhibited by NG-nitro-L-arginine + indomethacin and cysteine aminotransferase inhibitor aminooxyacetic acid in the normal SV. In contrast, ACh did not evoke relaxation in the distended SV (DSV). The concentration of H2S quantified by methylene blue assay in DSV was significantly lower than that in control. Transmission electron microscope and immunohistochemistry studies showed that the preparation destroyed the endothelium, smooth muscle, organelle, and vasa vasorum. We conclude that surgical preparation injures the endothelium and smooth muscle of the SV grafts and reduces H2S release from SV. These effects may contribute to the poor long-term patency of the SV graft.

Association Between Perfusate Oxygenation and Acute Lung Injury in Tetralogy of Fallot Surgery.

PURPOSE: Little is known regarding precise estimates of the association between perfusate oxygenation (PpO2) and acute lung injury (ALI) following tetralogy of Fallot repair. The objective is to investigate PpO2 and the risk of ALI following tetralogy of Fallot repair in pediatric patients. METHODS: We conducted a nested case-control study within a prospective Chinese TedaICH cohort including 134 ALI patients aged 1 month to 18 years undergoing complete repair of tetralogy of Fallot, and each was matched to two controls. We selected the highest PpO2 during aortic crossclamp as the exposure. Conditional logistic regression was used to quantify the association between PpO2 and overall ALI risk by covariates of interest. We identified and integrated the risk covariates to build ALI nomograms and internally validated the nomograms using bootstrapping. RESULTS: After adjusting for covariates, continuously and categorically higher PpO2 values were associated with ALI risk (all P < 0.05), especially for those with a z-score of pulmonary annulus < -4.0 (P = 0.002), McGoon ratio < 1.5 (P = 0.029), and major aortopulmonary collateral arteries (P = 0.005), despite no statistical heterogeneity (all P interaction >0.05). Younger age, lower oxyhemoglobin saturation, untreated minor aortopulmonary collateral arteries, transannular patch, larger transpulmonary gradient, major transfusion, and longer cardiopulmonary bypass time were independent risk factors for ALI (all P < 0.05). Combining the PpO2 nomogram provided further risk discriminative information on ALI diagnosis compared with the covariate-based nomogram alone in the training cohort (AUC 0.865, 95% CI [0.828-0.903] vs. 0.869 [0.832-0.906], respectively) with no statistical significance (P = 0.445). CONCLUSIONS: The findings suggested an association between high PpO2 and ALI risk, and more importance should be attached to independent risk factors for ALI.

Minimally invasive perventricular versus open surgical ventricular septal defect closure in infants and children: a randomised clinical trial.

BACKGROUND: Robust evidence is lacking regarding the clinical efficacy, safety and cardiopulmonary performance of perventricular closure. This study investigated the perioperative efficacy, safety and cardiorespiratory performance of perventricular closure of perimembranous ventricular septal defects (pmVSDs). METHODS: Operation-naïve infants and young children aged 5-60 months with isolated pmVSDs were randomised to receive either standard open surgical or minimally invasive perventricular closure via direct entry into the ventricle with a catheter from a subxiphoid incision. The primary outcomes included complete closure at discharge, major and minor adverse events and the changes in perioperative cardiorespiratory performance from baseline. Complete closure was mainly analysed in the modified intention-to-treat (mITT) population, with sensitivity analyses for the ITT, per-protocol (PP) and as-treated (AT) populations (non-inferiority margin -5.0%). RESULTS: We recruited 200 patients with pmVSDs for this study (mean age 24.38 months, range 7-58 months, 104 girls), of whom 100 were randomly allocated to one of the study groups. The non-inferiority of perventricular to surgical closure regarding complete closure at discharge was not shown in the ITT (absolute difference -0.010 (95% CI -0.078 to 0.058)) and mITT populations (-0.010 (95% CI -0.069 to 0.048)), but was shown in the PP (0.010 (95% CI -0.043 to 0.062)) and AT populations (0.048 (95% CI -0.009 to 0.106)). Perventricular closure reduced the rate of compromising cardiac haemodynamics, electrophysiological responses, cardiomyocyte viability, respiratory mechanics, ventilatory and gas exchange function and oxygenation and tissue perfusion compared with surgical closure (all between-group P<0.05). CONCLUSIONS: For infants and young children with pmVSD, perventricular closure reduced the rate of postoperative cardiorespiratory compromise compared with surgical closure, but the non-inferiority regarding complete closure should be interpreted in the context of the specific population. TRIAL REGISTRATION NUMBER: NCT02794584 ;Results.

Plasma protein profiling in patients undergoing coronary artery bypass grafting surgery and clinical significance.

This study was designed to identify the protein profiling in patients with triple vessel coronary artery disease (CAD) undergoing CABG, in order to detect CAD-related differential proteins in these patients. CABG patients with triple vessel disease with/without left main stenosis (n =160) were compared to normal coronary angiographic subjects (n =160). Plasma samples of 20 males and 20 females in each group were analyzed with iTRAQ technique. ELISA test was used to test the chosen proteins from iTRAQ results in plasma samples from a new cohort of the CABG group (n=120, male/femal=61/59) and control (n =120, male/female=60/60). iTRAQ detected 544 proteins with 35 up-regulated and 41 down-regulated (change fold > 1.2 or < 0.83, p < 0.05). Three proteins including platelet factor 4 (PF4), coagulation factor XIII B chain (F13B), and secreted frizzled-related protein 1 (sFRP1) were selected for validation by using ELISA that demonstrated significant up-regulation of PF4 and sFRP1 (p < 0.05). There was a positive correlation between these proteins and CAD (p < 0.05) and myocardial infarction history (p < 0.05). Thus, we for the first time have found 76 proteins differentially expressed in plasma of CABG patients. The thrombotic disease/inflammation progress-related protein PF4 and sFRP1, a member of the Wnt/fz signal-transduction pathway and related to myocardial repair, are significantly up-regulated in triple-vessel disease with/without left main stenosis. PF4 may be developed as a biomarker for the diagnosis of the severity of CAD requiring CABG procedure.

Accuracy of Multi-Slice Spiral Computed Tomography for Preoperative Tumor Node Metastasis (TNM) Staging of Colorectal Carcinoma.

BACKGROUND With the advances in imaging technologies, multi-slice spiral computed tomography (MSCT) has demonstrated superiority in the diagnosis and staging of colorectal carcinoma. In the current study, preoperative TNM staging of colorectal carcinoma by using MSCT was conducted and compared with the corresponding postoperative pathological examination findings, in order to evaluate the accuracy of preoperative MSCT for TNM staging. MATERIAL AND METHODS Combinations of biphasic or triphasic enhanced-phase MSCT scans were obtained for 76 patients with colorectal carcinoma, and the TNM stage was determined based on imaging reconstruction from various angles and perspectives to display the size, location, and affected range of tumors. The preoperative TNM stage was compared with the postoperative pathological stage, and the consistency between the 2 methods was tested by the k test using SPSS 17.0 software. RESULTS Among the different combinations of enhanced-phase MSCT scanning, triphasic MSCT imaging, comprising the arterial, portal venous, and delayed phases, showed the highest accuracy rates, at 81.6% (62/76), 82.89% (63/76), and 96.1% (73/76) for T, N, and M staging, respectively, with k values of 0.72, 0.65, and 0.56, respectively, indicating consistency with the postoperative pathological staging. CONCLUSIONS Combined MSCT scanning comprising the arterial phase, portal venous phase, and delayed phase showed satisfying consistency with the postoperative pathological analysis results for TNM staging of colorectal carcinoma. Thus, MSCT is an important clinical value for improving the accuracy of TNM staging and for planning the appropriate colorectal cancer treatment.

Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications.

BACKGROUND: Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internal mammary artery (IMA). METHODS: Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel. RESULTS: Benidipine caused more relaxation in KCl-contracted (86.7% ± 3.3%; n = 12) than in U46619-contracted (63.8% ± 5.3%; n = 8; p < 0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 ± 2.7 mN to 7.4 ± 1.2 mN; n = 6; p < 0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV)1.2 protein content (0.55 ± 0.02 versus 0.63 ± 0.02 mg/mL; p < 0.05). CONCLUSIONS: We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.

Comparison of effects of extra-thoracic paraaortic counterpulsation to intraaortic balloon pump on circulatory support in acute heart failure.

BACKGROUND: Previously designed intra-thoracic paraaortic counterpulsation device has limited stroke volume and may depress the lung to cause complications. The purpose of this study was to evaluate the hemodynamic effects of an extra-thoracic paraaortic counterpulsation device (ETPACD) in comparison to intraaortic balloon pump (IABP) in an animal model with acute heart failure. METHODS: The acute heart failure model was successfully induced by snaring branch of anterior descending coronary artery in sheep (weighting, 38-50 kg, n = 8). The ETPACD is a single port, 65-ml stroke volume blood chamber designed to be connected to descending aorta through a valveless graft and placed extra-thorax. In comparison, a standard clinical 40-ml IABP was placed in the descending aorta. The hemodynamic indices of both devices were recorded during counterpulsation assistance. Two of the sheep were allowed to survive for 1 week to examine the prolonged effect. RESULTS: Both ETPACD and IABP increased cardiac output with higher effect of ETPACD (13.52 % vs. 8.19 % in IABP, P < 0.05) and on mean diastolic aortic pressure (26.73 % vs. 12.58 % in IABP, P < 0.01). Both ETPACD and IABP also produced a greater reduction in left ventricular end-diastolic pressure (26.77 % vs. 23.08 %, P > 0.05). The ETPACD increased left carotid artery flow more significantly the IABP (18.00 % vs. 9.19 % , P < 0.05). In two of the sheep allowed to survive for 1 week, the device worked well with no complications and there was no thrombus formation in the chamber of ETPACD. CONCLUSIONS: This study demonstrated that both ETPACD and IABP provided benefit of circulatory support in acute heart failure with better effect on hemodynamic parameters provided by ETPACD. Therefore, ETPACD with theoretical larger stroke volume may become a promising counterpulsation device for treatment of heart failure.

Acute phase proteins altered in the plasma of patients with congenital ventricular septal defect.

PURPOSE: Ventricular septal defect (VSD) has intracardiac left-to-right shunt and increased pulmonary flow that may affect the acute phase response (APR). We examined the hypothesis that plasma proteins of VSD patients may be altered. EXPERIMENTAL DESIGN: 2DE and MS were used to detect differential plasma proteins in VSD patients (n = 55) and controls (n = 70). Candidate APR proteins were confirmed by ELISA in new samples. RESULTS: Among three differentially expressed APR proteins from 322 protein spots detected, haptoglobin (0.4 ± 0.04 versus 0.6 ± 0.07 mg/mL; p = 0.016) and serum amyloid P-component (SAP) (3.8 ± 0.2 versus 6.3 ± 0.8 ng/mL; p = 0.003) were significantly lower and orosomucoid 2 (3.1 ± 0.1 mg/mL versus 2.3 ± 0.1 mg/mL; p < 0.001) was significantly higher in VSD patients than in normal controls. CONCLUSIONS AND CLINICAL RELEVANCE: The plasma concentration of three acute phase proteins, haptoglobin, SAP, and orosomucoid 2 are altered that may reflect inflammation, be associated with decreased innate immune system function, and predispose the VSD patients to vulnerability to infections and pulmonary disease. These three proteins in plasma may also be developed as biomarkers for the function of innate immune system in patients with congenital heart disease.

Bone marrow mesenchymal stem cells improve myocardial function in a swine model of acute myocardial infarction.

The aim of the current study was to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute myocardial infarction (AMI). AMI was induced in mini­swine by ligating the left anterior descending coronary artery, and BMSCs (1x107) were injected via a sterile microinjection into the ischemic area. Six months postoperatively, electrocardiograph­gated single photon emission computed tomography revealed that the myocardial filling defect was reduced and the left ventricular ejection fraction was improved in the BMSC group compared with the control group (P<0.05). Histopathological examination indicated that, in the BMSC treatment group, the percentage of survived myocardial tissue and the vessel density were increased, and the percentage of apoptosis was decreased compared with controls (P<0.05). Reverse transcription­polymerase chain reaction results indicated that the expression levels of multiple inflammatory factors were significantly upregulated in the BMSC group compared with levels in the control group (P<0.05). In conclusion, the present study demonstrated that BMSC injection significantly improved cardiac function and reduced infarct size in six months, indicating that this method may be valuable for future study in clinical trials.

Suxiao jiuxin pill induces potent relaxation and inhibition on contraction in human artery and the mechanism.

Suxiao Jiuxin Pill, a compound Chinese traditional medicine with main components of tetramethylpyrazine and borneol, is widely used for antiangina treatment in China but its pharmacological effect on human blood vessels is unknown. We investigated the effect and possible mechanism of SJP in the human internal mammary artery (IMA, n = 78) taken from patients undergoing coronary surgery. SJP caused full relaxation in KCl- (99.4 ± 10.5%, n = 6) and U46619- (99.9 ± 5.6%, n = 6) contracted IMA. Pretreatment of IMA with plasma concentrations of SJP (1 mg/mL), calculated from the plasma concentration of its major component borneol, significantly depressed the maximal contraction to KCl (from 35.8 ± 6.0 mN to 12.6 ± 5.6 mN, P = 0.03) and U46619 (from 19.4 ± 2.9 mN to 5.7 ± 2.4 mN, P = 0.007) while SJP at 10 mg/mL abolished the subsequent contraction. Endothelium denudation and inhibition of eNOS significantly altered the SJP-induced relaxation without changes of eNOS expression. We conclude that SJP has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors in human arteries. The vasorelaxation involves both endothelium-dependent and -independent mechanisms. Thus, the effect of SJP on human arteries demonstrated in this study may prove to be particularly important in vasorelaxing therapy in cardiovascular disease.

Proteomic study reveals plasma protein changes in congenital heart diseases.

BACKGROUND: Congenital heart disease (CHD) is the most common birth defect in newborns. Plasma proteins may serve as indicators of disease and are a rich source for biomarker discovery, but little has been studied in CHD. We examined the hypothesis that plasma proteins may be altered and related to the pathologic changes of CHD. METHODS: Differential protein analysis was performed in the plasma of patients with tetralogy of Fallot, isolated ventricular septal defect, and normal controls by using two-dimensional electrophoresis and mass spectrometry. Candidate proteins that might be related to disease processes were further confirmed by enzyme-linked immunosorbent assay in the new samples (n=40). RESULTS: Identified were 18 differentially expressed protein spots and 10 corresponding proteins or polypeptides. Among those, 2 downregulated proteins, gelsolin, ficolin-3, with significant clinical relevance, were further analyzed for validation. The plasma levels of gelsolin (76.30±4.42 vs 131.80±23.46 µg/mL in control; p=0.025, n=40 in each group) and ficolin-3 (4.93±0.36 vs 10.58±1.58 µg/mL in control; p=0.001, n=40 in each group) in tetralogy patients were significantly lower than those in normal controls. The ficolin-3 plasma level was also lower in the patients with isolated VSD (5.55±0.34 vs 10.58±1.58 µg/mL in control µg/mL; p=0.003, n=40 in each group). CONCLUSIONS: We used proteomic methods to demonstrate for the first time the plasma protein changes in CHD patients that may reveal the possible mechanisms for the prolonged bleeding time in tetralogy patients and the susceptibility to pulmonary infections in patients with CHDs. These findings have strong clinical implications.