Biomechanical characterization of a novel ring connector for sutureless aortic anastomosis.

The surgical treatment for aortic diseases remains a challenge for any cardiac surgeon. The use of sutureless ring connector in aortic anastomosis can simplify the procedure and shorten anastomosis time. Therefore, we developed a novel device for sutureless aortic anastomosis. A series of experiments were carried out for tensile and leakproof-capacity assessments to verify the feasibility of the ring connector by using fresh swine aorta samples. In in vivo test, the ring connector was implanted in 6 swine with follow-up of 6 months. Radiographic and pathological studies of the aorta were performed. In the tensile tests, the strength was 32.7±5.9 Newton (N) in the sutureless anastomosis group, compared with 73.3±12.5 N in the control group by traditional manual suture. In the leakproof-capacity assessment, no sign of either leakage or bursting was evident at 280 mmHg of internal pressure in the aorta samples. In in vivo tests, it took 9.47±0.3 minutes for the sutureless anastomosis, compared with 15.58±1.39 minutes for hand-sewn suturing. Insertion was easy and rapid. Radiographic and pathological studies were performed at first month, third month and sixth month after surgery, each time obtained from the two swine, showed patency of the anastomosis and no signs of stenosis, blood leakage, migration or pseudoaneurysm formation, except one paralyzed swine developed of thrombo-occlusion at the site of the sutureless anastomosis. The result indicates that this novel ring connector offers considerable promise for sutureless aortic anastomosis.

Safety and feasibility of chronic transvenous phrenic nerve stimulation for treatment of central sleep apnea in heart failure patients.

INTRODUCTION: Central sleep apnea (CSA) is common in patients with heart failure (HF) and is associated with poor quality of life and prognosis. Early acute studies using transvenous phrenic nerve stimulation (PNS) to treat CSA in HF have shown a significantly reduction of CSA and improvement of key polysomnographic parameters. In this study, we evaluated the safety of and efficiency chronic transvenous PNS with an implanted neurostimulator in HF patients with CSA. METHODS: This study was a prospective, nonrandomized evaluation of unilateral transvenous PNS in eight HF patients with CSA. The stimulation lead, which connected to a proprietary neurostimulator, was positioned in either the left pericardiophrenic or right brachiocephalic vein. Monitoring during implantation and 6-monthly follow-ups were performed. RESULTS: Six of the implanted eight patients completed the study (one was lost to follow-up; one died from pneumonia). Neither side effects nor adverse events related to stimulation occurred. During the 6-monthly follow-ups, one patient had a lead dislodgement in the first month and the lead was subsequently repositioned. No additional lead dislodgements occurred. There were no significant changes in sleep habits, appetite, bleeding or infections. Compared with the parameters before stimulator implantation, there were significant improvement in apnea-hypopnea index, central apnea index, left ventricular ejection fraction and 6-min walk distance (all P < 0.01). CONCLUSIONS: Use of chronic transvenous PNS appears to be safe and feasible in HF patients with CSA. Large multicenter studies are needed to confirm safety and efficacy in this population.

Obstructive Sleep Apnea Increases the Perioperative Risk of Cardiac Valve Replacement Surgery: A Prospective Single-Center Study.

STUDY OBJECTIVES: Sleep apnea is common in patients referred for cardiac valve replacement (CVR). We aimed to determine the association of obstructive sleep apnea (OSA) and central sleep apnea (CSA) with perioperative events in CVR surgery in patients with rheumatic valvular heart disease (RVHD). METHODS: Between April 2010 and April 2014, 290 patients with RVHD undergoing CVR were screened for sleep apnea 1 to 7 days before CVR. Baseline medications, cardiac function, sleep parameters, perioperative events, and related risk factors were evaluated. RESULTS: OSA patients had longer duration of intensive care unit (ICU) stay and mechanical ventilation compared with no sleep-disordered breathing and CSA patients. Patients with CSA had a higher rate of pacemaker use and higher first dose of dobutamine in ICU. NYHA Class and the presence of OSA were independently associated with overall worsening of postoperative recovery (ICU stay ≥ 25 h). Age, NYHA class, and the presence of OSA were independently associated with postoperative respiratory insufficiency (mechanical ventilation ≥ 20 h). Preoperative atrial fibrillation, pulmonary hypertension, and OSA were independently associated with postoperative pacemaker use. CONCLUSIONS: RVHD patients with OSA have an increased incidence of perioperative adverse events. OSA was independently associated with overall postoperative recovery, respiratory insufficiency, and higher rate of postoperative pacemaker use, while CSA was not associated with postoperative events.

Adiponectin protects rat heart from left ventricular remodeling induced by chronic intermittent hypoxia via inhibition of TGF-ß/smad2/3 pathway.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders. Chronic intermittent hypoxia (CIH) is the primary player in OSAS of the many associated factors. This study was in order to investigate the effects of the Adiponectin (Ad) on left ventricular remodeling induced by CIH. METHODS: Forty-five rats were randomly divided into three groups: normal control (NC) group, CIH group and CIH plus Ad supplemented (CIH + Ad) group. After 35 days' CIH exposure, masson analysis was used to detect the left ventricular fibrosis and western blot was used to measure the protein expression of collagen I, collagen III and TGF-ß/smad2/3 pathway. Gene analysis by RT-PCR was used to study the MMP2 and TIMP2. RESULTS: After CIH exposure, the fibrosis of left ventricular in CIH group was significantly remarkable than that in both NC and CIH + Ad groups (P<0.05), although statistical difference existed between NC and CIH + Ad groups (P<0.05). In addition, the protein expression of collagen I as well as collagen III and the ratio of mRNA levels of MMP2/TIMP2 were the highest in CIH group but the lowest in NC group, with CIH + Ad group in between. There was a significant difference among three groups (all P<0.05). The TGF-ß/smad2/3 pathway was activated obviously in CIH group, but less noticeably in CIH + Ad group (P<0.05) with a significant difference in the two groups. CONCLUSIONS: The present study showed that Ad could ameliorate the left ventricular remodeling induced by CIH via inhibition of the expression of TGF-ß/smad2/3 pathway.

Elimination of central sleep apnea by cardiac valve replacement: a continuous follow-up study in patients with rheumatic valvular heart disease.

BACKGROUND: Recent studies have suggested that cardiac surgery may affect sleep-disordered breathing (SDB) in chronic heart failure patients. However, the dynamic changes in sleep apnea and heart function after cardiac surgery and the mechanisms responsible for these changes remain unknown. METHODS: Patients with rheumatic valvular heart disease (RVHD) and SDB were enrolled and followed up at three, six and 12 months after cardiac valve replacement (CVR). Baseline and follow-up clinical data consisting of NYHA classification, 6min walk distance (6-MWD), medications, echocardiography, electrocardiography, chest X-ray, arterial blood gas, lung-to-finger circulation time (LFCT), and sleep data were collected and evaluated. RESULTS: Twenty-four central sleep apnea (CSA) patients and 15 obstructive sleep apnea (OSA) patients completed three follow-up assessments. Comparison of the baseline parameters between OSA patients and CSA patients showed that CSA patients had a worse baseline cardiac function assessed by higher NYHA class, shorter 6-MWD, larger left atrial diameter, longer LFCT, and enhanced chemosensitivity (higher pH and lower arterial carbon dioxide tension (PaCO2)). A continuous significant elevation in 6-MWD and left ventricular ejection fraction and decrease in NYHA class, plasma BNP, and left atrial diameter were found in both CSA and OSA patients. When comparing CSA and OSA patients, the CSA indices were remarkably reduced at month 3 post CVR and sustained throughout the trial, whereas there were no significant decreases in OSA index and hypopnea index. pH values and LFCT were markedly decreased and PaCO2 markedly increased in patients with CSA at the end of the third months following CVR. These changes were sustained until the end of the trial. CONCLUSIONS: CSA patients with RVHD had a worse baseline cardiac function, enhanced chemosensitivity and disordered hemodynamic as compared with OSA patients with RVHD. CSA were eliminated after CVR; however, there were no changes in OSA. The elimination of CSA, post CVR, is associated with the combined efficacies of improvement of cardiac function, normalized chemosensitivity, and stabilized hemodynamic.

Electrophysiological phenotypes of MeCP2 A140V mutant mouse model.

AIMS: MeCP2 gene mutations are associated with Rett syndrome and X-linked mental retardation (XLMR), diseases characterized by abnormal brain development and function. Recently, we created a novel MeCP2 A140V mutation mouse model that exhibited abnormalities of cell packing density and dendritic branching consistent with that seen in Rett syndrome patients as well as other MeCP2 mutant mouse models. Therefore, we hypothesized that some deficits of neuronal and synaptic functions might also be present in the A140V mutant model. METHODS: Here, we tested our hypothesis in hippocampal slices using electrophysiological recordings. RESULTS: We found that in young A140V mutant mice (3- to 4-week-old), hippocampal CA1 pyramidal neurons exhibited more positive resting membrane potential, increased action potential (AP) firing frequency induced by injection of depolarizing current, wider AP duration, and smaller after hyperpolarization potential compared to neurons prepared from age-matched wild-type mice, suggesting a neuronal hyperexcitation. At the synaptic level, A140V mutant neurons exhibited a reduced frequency of spontaneous IPSCs (inhibitory postsynaptic potentials) and an enhanced probability of evoked glutamate release, both suggesting neuronal hyperexcitation. However, hippocampal CA1 long-term potentiation was not significantly different between A140V and WT mice. In adult mice (11- to 13-month-old), in addition to neuronal hyperexcitation, we also found significant deficits of both short-term and long-term potentiation of CA3-CA1 synapses in A140V mice compared to WT mice. CONCLUSIONS: These results clearly illustrate the age-dependent abnormalities of neuronal and synaptic function in the MeCP2 A140V mutant mouse model, which provides new insights into the understanding of the pathogenesis of Rett syndrome.

Overnight fluid shifts in subjects with and without obstructive sleep apnea.

OBJECTIVE: To investigate the characteristics of baseline body fluid content and overnight fluid shifts between non-obstructive sleep apnea (non-OSA) and obstructive sleep apnea (OSA) subjects. METHODS: A case-controlled study was performed between February 2013 and January 2014, with 36 (18 OSA and 18 non-OSA) outpatients enrolled in this study. Polysomnographic parameters and results of body fluid were compared between the two groups. RESULTS: There were no differences in age, weight, and body mass index (BMI) between groups. Compared with the non-OSA group, OSA group had significantly higher neck circumference (NC) and fluid volume shift in the legs. OSA patients had higher left and right leg fluid indices than non-OSA subjects. There were significant correlations between apnoea-hypopnoea index and baseline fluid indices in both legs as well as the reduction in overnight change in both legs fluid volume. The increase in NC was also significantly correlated with the reduction in overnight change in both legs fluid volume, but not with the change in head and neck fluid volume. There were significant correlations between change in NC and increased fluid shifts in head and neck volume. CONCLUSIONS: OSA patients had a higher baseline fluid content in both legs as compared with non-OSA subjects, which may be the basic factor with regards to fluid shifts in OSA patients. The increase in head and neck fluid shift volume did not directly correlate with the severity of OSA.

Prevalence and risk factors of sleep disordered breathing in patients with rheumatic valvular heart disease.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) is common in patients with chronic heart failure secondary to non-valvular heart disease; however, the prevalence and characteristics of SDB in patients with rheumatic valvular heart disease (RVHD) are unclear. This study was designed to determine the prevalence, characteristics, and risk factors for SDB in RVHD patients. METHODS: A cross-sectional study was conducted in 260 RVHD patients. The following data were recorded: types of heart valve lesions, electrocardiographic, echocardiographic, arterial blood gas analysis findings, baseline medication, 6-minute walk test (6MWT) distance, and sleep parameters. RESULTS: Compared to patients with single leftsided valve lesions, patients with left- and rightsided valve lesions had a higher prevalence of SDB (46.2% vs. 31.2%, p = 0.013); the increased prevalence of SDB only involved central sleep apnea (CSA) (31.1% vs. 14.1%, p = 0.001). Patients with obstructive sleep apnea (OSA) or CSA were older and had a shorter 6MWT distance, lower left ventricle ejection fraction and PaO2, a longer lung-to-finger circulation time, and a higher prevalence of atrial fibrillation (AF) and hypertension (all p < 0.05) as compared with patients without SDB. Multinomial logistic regression analysis showed that PaO2 ≤ 85 mm Hg was the only risk factor for OSA. Male gender, AF, 6MWT distance ≤ 300 m, PaO2 ≤ 85 mmHg, and PaCO2 ≤ 40 mm Hg were risk factors for CSA. CONCLUSIONS: Patients with RVHD had a high prevalence of SDB (predominantly CSA). RVHD patients with SDB, particularly those who had CSA, manifested more severe symptoms and greater impairment of cardiac function. Assessments of clinical manifestations of cardiac dysfunction may be important for predicting the risk factors for SDB.

Invasive examinations in patients with suspected lung cancer: more may be too many.

The recent article entitled "Principles of biopsy in suspected lung cancer: priority still based on invasion in the era of targeted therapy?" published in Journal of Thoracic Disease by Chen et al., concluded the principles of biopsy in suspected lung cancer should be prioritized in sequence based on weight in clinical management, acquisition of tissue, invasion, efficiency and cost. We reported a patient with a 30-year history of pulmonary silicosis, had been found no evidence of tumor after receiving a series of invasive examinations. We conclude that invasive examinations should be limited in patients with suspected lung cancer who had a defined history of underlying disease. Minimal invasion with careful acquisition of the appropriate quantity and quality of tissue should be adequate.

Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction.

The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 µM iptakalim or the combination of 10 µM iptakalim and 1, 10 and 100 µM glibenclamide for 24 h, and the eNOS activity and NO levels were measured in the conditioned medium from the HPAEC cultures. The eNOS activity and NO levels were reduced significantly in the conditioned medium from HPAEC cultures under hypoxic conditions. Pre-treatment with 10 µM iptakalim normalized the reduction of the eNOS activity and NO levels caused by hypoxia in the conditioned medium from HPAEC cultures. Iptakalim raised the eNOS activity and NO levels under hypoxic conditions, but was blocked by the K(ATP) channel blocker, glibenclamide. Our results indicate that hypoxia impairs NO system function, whereas the ATP-sensitive K(+) channel opener, iptakalim, may rescue HPAECs from hypoxia-induced NO system dysfunction.

Coronary artery bypass grafting in a patient with history of esophagectomy, hypothyroidism, hypertension and type 2 diabetes mellitus: a case report.

Coronary artery bypass grafting (CABG) is a mature procedure in treating patients with coronary artery diseases. We report a patient undergoing CABG had history of esophageal cancer and multiple underlying diseases: hypothyroidism, type 2 diabetes mellitus and hypertension. A CABG with midline sternotomy was safely performed in the presence of thyroid replacement therapy and intensive control of blood pressure and blood glucose. The patient recovered postoperatively with supportive care.

Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study.

BACKGROUND: Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. Phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF. We report the clinical use of transvenous PNS in patients with CHF and CSR. METHODS: Nineteen patients with CHF and CSR were enrolled. A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA. RESULTS: Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate as well as improvement in oxygen saturation was seen. Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% ± 1.6% vs 94.3% ± 0.9% and 80.3% ± 3.7% vs 88.5% ± 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, P = .36). CONCLUSIONS: The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events.

[Proteomic analysis of the effect of noradrenalin on human pulmonary arterial smooth muscle cells].

OBJECTIVE: To observe the effect of noradrenalin (NE) on human pulmonary arterial smooth muscle cells (PASMC) by using a proteomic approach. METHODS: Human PASMC were cultured primarily in vitro. Experiments were performed in the 3(rd) to 5(th) passages of the cells. The human PASMC were cultured in serum-free medium for 24 h prior to treatment with either NE (10(-5) mol/L, the test group) or completed-serum culture medium (the control group) for 24 h. And then analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was performed to display the different protein profiles of whole cell protein from cultures of the control and the NE-treatment group. Real-time RT-PCR and Western blot analysis were used to confirm the proteomic analysis. RESULTS: The purity of the primary culture cells was about 99%. When the human PASMC were treated by NE, the expression of different groups of cellular proteins was changed, including cell cytoskeleton-associated proteins, cell signal-associated proteins, and glycolytic and metabolism-associated proteins. The results were confirmed using real-time RT-PCR and Western blot. NE enhanced the proliferation of human PASMC partly by affecting the expression of α-enolase. CONCLUSION: The data suggest that a wide range of signaling pathways may be involved in NE-induced proliferation of human PASMC, and α-enolase associated pathway may be an important one.

Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth muscle cell proliferation.

AIM: To investigate the anti-proliferative effect of iptakalim (Ipt), a newly selective K(ATP) channel opener, in endothelin-1 (ET-1)-induced human pulmonary arterial smooth muscle cells (PASMCs) using proteomic analysis. METHODS: Human PASMCs were incubated with ET-1 (10(-8) mol/L) and ET-1 (10(-8) mol/L) plus iptaklim (10(-5) mol/L) for 24 h. Analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was employed to display the different protein profiles of whole-cell protein from cultures of control, ET-1 treatment alone, and treatment with ET-1 and iptaklim combined. Real time RT-PCR and Western blot analysis were used to confirm the proteomic analysis. RESULTS: When iptakalim inhibited the proliferative effect of ET-1 in human PASMCs by opening the K(ATP) channels, the expression of different groups of cellular proteins was changed, including cytoskeleton-associated proteins, plasma membrane proteins and receptors, chaperone proteins, ion transport-associated proteins, and glycolytic and metabolism-associated proteins. We found that iptakalim could inhibit the proliferation of human PASMCs partly by affecting the expression of Hsp60, vimentin, nucleoporin P54 (NUP54) and Bcl-X(L) by opening the K(ATP) channel. CONCLUSION: The data suggest that a wide range of signaling pathways may be involved in abolishing ET-1-induced proliferation of human PASMCs following iptakalim treatment.