LncRNA NEAT1/miR-211/IL-10 Axis Regulates Inflammation of Peripheral Blood Mononuclear Cells in Acute Myocardial Infarction.

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

Role of Bone Morphogenetic Protein 4 in the Inflammation of the Myocardium and Vascular Tissue of Obese Mice.

ABSTRACT: Bone morphogenetic protein 4 (BMP4) is a proinflammatory factor. The expression of BMP4 is reduced in the adipose and enhanced in the myocardium and vascular during obesity. It is possibly involved in the process of inflammatory response of the myocardium and vascular. Obesity, often regarded as a risk factor for cardiovascular diseases, is a kind of inflammatory response. This study aimed to investigate the relationship of BMP4 with obesity and cardiovascular disease. Ob/ob mice were used as the experimental group, and C57BL/6 mice were used as the control group. The two groups were further divided into 2 subgroups based on the mice carrying adenovirus-encoding shRNA for BMP4 or Lac Z genes. The messenger RNA and protein levels of BMP4, interleukin-1ß, and interleukin-9 were significantly higher in the myocardial tissue and aorta of ob/ob+ Lac Z shRNA than those in the other 3 groups, whereas the levels in the ob/ob+ BMP4 shRNA group were significantly decreased and comparable with those in the control groups. BMP4 is significantly upregulated in the myocardial tissue and aorta of obese mice, and this suggests that BMP4 is an risk factor involved in the local inflammatory response.

Percutaneous valved stent implantation in the ascending aorta for the treatment of very high-risk aortic regurgitation: an animal study.

PURPOSE: We investigated the effects of percutaneous valved stent implantation in the ascending aorta as an alternative treatment for aortic regurgitation in a canine model. MATERIALS AND METHODS: A total of 16 healthy dogs weighing an average of 18.3 ± 2.1 kg were used for the establishment of animal models of chronic aortic regurgitation by percutaneous aortic valve perforation and balloon dilation. At 2 mo after successful model establishment, all experimental animals underwent valved stent implantation in the ascending aorta and then were followed up for 3 mo. RESULTS: Experimental models of chronic aortic regurgitation were successfully established in 10 dogs. Surviving dogs underwent successful valved stent implantation in the ascending aorta and were subsequently followed up for 3 mo. The level of instantaneous aortic regurgitation at 3-mo follow-up was significantly reduced compared with that before valved stent implantation (2.4 ± 0.9 versus 10.6 ± 2.1 mL/s, P < 0.05). The left ventricular ejection fraction was significantly increased (53.8 ± 4.2% versus 37.8 ± 3.7%, P < 0.05), and the left ventricular end-diastolic volume was also significantly reduced (30.3 ± 2.2 versus 40.1 ± 3.6 mL, P < 0.05). No paravalvular leak, stroke, atrioventricular block, or other complications occurred in dogs undergoing valved stent implantation. CONCLUSIONS: Percutaneous valved stent implantation in the ascending aorta is feasible, effective, and safe as an alternative treatment for very high-risk aortic regurgitation in a canine model.

[Serum parathyroid hormone levels predict hospitalization in outpatients of heart failure: a preliminary study].

OBJECTIVE: To evaluate the predicative value of serum parathyroid hormone (PTH) levels in outpatients of heart failure (HF) for hospitalization. METHODS: A total of 102 consecutive HF outpatients were enrolled. The receiver operating characteristic (ROC) curves demonstrated the optimal cut-off points of PTH levels for hospitalization due to HF. And Logistic regression analysis model was employed to analyze the independent association between PTH and hospitalization for HF. RESULTS: The more advanced grade of New York Heart Association (NYHA), the higher serum level of PTH. The ROC curves showed PTH levels ≥ 56.05 ng/L were the optimal cut-off point for hospitalization for HF with a sensitivity of 90.0%, a specificity of 89.2% and the area under ROC curve of 0.92. After adjustment for predictors for hospitalization due to HF (gender, age, diabetes mellitus, hypertension, left ventricular ejection fraction, estimated glomerular filtration rate and brain natriuretic peptide), PTH levels were associated with hospitalization due to HF (OR = 1.282, 95%CI 1.026-1.362). CONCLUSION: The serum level of PTH in HF outpatients is an independent predicator for hospitalization due to HF.

PTH Predicts the in-Hospital MACE After Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction.

Objective: To investigate the correlation between serum parathyroid hormone (PTH) levels and in-hospital major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI), and establish a risk prediction model based on parameters such as PTH for in-hospital MACE. Methods: This observational retrospective study consecutively enrolled 340 patients who underwent primary PCI for STEMI between January 2016 and December 2020, divided into a MACE group (n=92) and a control group (n=248). The least absolute shrinkage and selection operator (LASSO) and logistic regression analyses were used to determine the risk factors for MACE after primary PCI. The rms package in R-studio statistical software was used to construct a nomogram, to detect the line chart C-index, and to draw a calibration curve. The decision curve analysis (DCA) method was used to evaluate the clinical application value and net benefit. Results: Correlation analysis revealed that PTH level positively correlated with the occurrence of in-hospital MACE. Receiver operating characteristic curve analyses revealed that PTH had a good predictive value for in-hospital MACE. Multivariate logistic regression analysis indicated that Killip class II-IV, and FBG were independently associated with in-hospital MACE after primary PCI. A nomogram model was constructed using the above parameters. The model C-index was 0.894 and the calibration curve indicated that the model was well calibrated. The DCA curve suggested that the nomogram model was better than TIMI score model in terms of net clinical benefit. Conclusion: Serum PTH levels in patients with STEMI are associated with in-hospital MACE after primary PCI, and the nomogram risk prediction model based on PTH demonstrated good predictive ability with obvious clinical practical value.

Percutaneous valved stent implantation above the coronary ostia.

BACKGROUND: In recent years, some experimental and clinical studies on transcatheter aortic valve implantation (TAVI) have been conducted. TAVI is indicated in patients with calcified pure or predominant aortic stenosis. The risk of this technique is still high. Aortic valved stent implantation above the coronary ostia might avoid blocking the coronary ostia. METHODS AND RESULTS: Twenty healthy dogs were selected to establish a canine model of acute aortic valve rupture. The dogs were randomly divided into 2 groups: the rupture model group without any treatment and the valved stent group with percutaneous valved stent implantation above the coronary ostia. The 2 groups of animals were followed up for 3 months. Echocardiography and other tests were performed to assess aortic regurgitation and ventricular function. Acute aortic valve rupture models were successfully established in 16 of 20 dogs. In the rupture model group, the mean aortic regurgitation was 6.8 ± 1.9 ml/s; only 3 of 8 animals survived for 3 months. In the valved stent group, the mean aortic regurgitation was 7.0 ± 2.1 ml/s; valved stents were successfully implanted in 8 animals. Instant post-implantation anatomy showed that the stents were located appropriately. Seven dogs survived for 3 months. CONCLUSIONS: Percutaneous valved stent implantation above the coronary ostia is feasible and effective as a transitional treatment for acute aortic valve rupture.

An integrated pericardial valved stent special for percutaneous tricuspid implantation: an animal feasibility study.

BACKGROUND: Various percutaneous valve replacement approaches have been reported in animals to replace the aortic and pulmonary valve. To broaden the indications of percutaneous approach to atrioventricular valves replacement, we developed a novel valved stent and evaluated the feasibility and safety of percutaneous implantation of the device in the tricuspid position. MATERIALS AND METHODS: A unidirectional semilunar valve of porcine pericardium was sutured to a valvular ring. Then the ring with pericardial valve was mounted on a double-edge nitinol stent to construct the tricuspid valved stent. Transcatheter tricuspid valved stent implantation was performed on 10 healthy sheep. These sheep were followed up shortly after procedure with echocardiography evaluation and 64-slice CT imaging examination during the periodical follow-up at 1 mo and at 6 mo post-implantation. Additionally, two sheep were sacrificed after the procedure for anatomic and histological evaluation one at 1 h and the other at 1 mo, respectively. RESULTS: Percutaneous valve implantation was successful in eight of 10 sheep. Two sheep died during the procedure due to migration of stent and fatal arrhythmia. The pressure of right heart did not significantly change after the procedure. Further echocardiography and imaging confirmed the stents were in desired position during the follow-up. The remaining six sheep with normal valvular and cardiac functionality survived for 6 mo after implantation. CONCLUSIONS: The tricuspid stent with a valvular ring and pericardial valve can be implanted in tricuspid annulus percutaneous. The double-edge stent could substitute the native tricuspid valve chronically.

Serum parathyroid hormone levels in patients with chronic right heart failure.

Parathyroid hormone (PTH) is a novel cardiovascular biomarker which is particularly useful for detection and assessment of heart failure (HF). However, previous studies examining PTH in heart failure have primarily focused on left HF; thus, the relationship between PTH and right HF remains unclear. The aim of the present study was to evaluate the serum PTH levels in patients with chronic right HF. A total of 154 patients with chronic right HF were enrolled in the present study. A binary logistic regression analysis model was used to assess the independent predictive value of PTH levels in chronic right HF. Partial correlative analysis was used to demonstrate the relevance of PTH levels on the parameters of assessment of right heart function. A multiple linear regression analysis model was used to evaluate the independent factors of PTH levels in patients with right HF. The results showed that the serum PTH levels in the right HF group were significantly higher compared with the control group. After adjusting for predictors of right HF, serum PTH levels were associated with right HF with an odds ratio of 1.066 (95% confidence interval: 1.030-1.102, P<0.001. Serum PTH levels were independently correlated with plasma N-terminal pro-B-type natriuretic peptide levels, right ventricular end-diastolic diameter and severity of lower extremity edema (all P<0.05). Therefore, based on the results of the present study, PTH may be a useful biomarker for detection and assessment of right HF.

[Transcatheter pulmonary valve replacement in sheep: 6-month evaluation of self-expanding valved stents].

OBJECTIVE: The purpose of this study was to determine the feasibility of transcatheter pulmonary valve replacement in sheep up to 6 months post procedure. METHODS: Fresh sheep pericardium treated with a 0.6% glutaraldehyde solution for 36 hours was sutured to a valvular ring and then fixed onto a newly designed nitinol self-expandable stent. Thoracotomy was performed in sheep (23.5 +/- 3.1) kg under general anesthesia and the device was delivered into the native pulmonary valve of the sheep via the anterior wall of right ventricle by catheter and fooled for 6 months. RESULTS: One sheep died 4 months after the procedure due to in-stent thrombosis. Another 4 animals survived the 6-month observing period. Angiographic and hemodynamic measurements confirmed good positioning and function of the stents with a competent valve immediately post procedure and 6 months post the procedure in surviving animals. CONCLUSION: Implantation of the nitinol self-expandable stent in the pulmonary valve position by a transcatheter approach is feasible and good function of transcatheter implanted memory nitinol valved stents was shown after 6 months of implantation in sheep.

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal-regulated protein kinase 1/2 and nuclear factor-κB signaling pathways.

Vascular calcification (VC) occurs in patients with chronic kidney disease (CKD) and contributes to cardiovascular dysfunction and mortality. Parathyroid hormone (PTH) is a crucial regulator of VC. High PTH serum levels constitute as a major risk factor for patients with CKD. However, the effect and mechanism of PTH on osteoblastic differentiation in endothelial cells have not been fully elucidated. In the present study, the role of PTH in VC was investigated using an in vitro calcification model. Endothelial cells were stimulated with PTH in the femto- to picomolar range. As determined by western blot analysis and ELISA, osteoblastic differentiation, as indicated by the BMP2 marker, occurred with maximum effect at 1×10-10 mmol/l PTH. The results indicate that PTH promotes osteoblastic differentiation of endothelial cells, as demonstrated by the increased expression of bone morphogenetic protein (BMP) 2 and BMP4. In addition, western blot analysis revealed that PTH activated the extracellular signal-regulated protein kinase (Erk)1/2 and nuclear factor (NF)-κB signaling pathways. However, reverse transcription-quantitative polymerase chain reaction demonstrated that inhibitors specific to Erk1/2 and NF-κB eradicated the effect of PTH treatment on BMP2, BMP4, ALP and RUNX2 expression. These results demonstrate that PTH promotes the osteoblastic differentiation of endothelial cells via the Erk1/2 and NF-κB signaling pathways, which suggests a potential role of PTH in the promotion of VC. These findings provide an insight into the association between PTH and cardiovascular disease.

Effect of parathyroid hormone on cardiac function in rats with cardiomyopathy.

The present study investigated the role of parathyroid hormone (PTH) in non-ischemic cardiomyopathy (CM) and its underlying mechanism. A total of 30 Sprague-Dawley male rats were randomly divided into a control group (n=6) and an experimental group (n=24). To induce CM in the rats of the experimental group, 2 mg/kg Adriamycin (ADR) was administered intraperitoneally with 5 equal injections every third day followed by 5 weekly injections resulting in a cumulative dose of 20 mg/kg. Following establishment of the model, rats in the experimental group were subdivided into a PTH-untreated CM group that received daily normal saline subcutaneous injections for 7 days and three treated CM groups that received daily subcutaneous injections of 5, 10, or 20 µg/kg of recombinant PTH for 7 days. Rats in the control group accordingly received intraperitoneal and subcutaneous injections of normal saline. Blood sample analysis revealed that B-type natriuretic peptide (BNP), troponin T, C-reactive protein (CRP), creatinine and phosphorus concentrations were increased in the PTH-untreated CM group compared with that in the control group, whereas PTH and calcium concentrations were decreased. Administration of PTH dose-dependently decreased BNP, CRP, creatinine and phosphorus levels, and increased PTH and calcium levels. Notably, there were significant differences in PTH, BNP, troponin T, CRP, creatinine, calcium, and phosphorus levels among the rats in the five groups (P<0.01). Cardiac ultrasonography results indicated that the left ventricular ejection fraction (LVEF) was significantly decreased in rats treated with ADR compared with the rats from the control group (P<0.01). However, the LVEF gradually recovered with elevated PTH treatment doses. The overall differences of LVEF and left ventricular end-systolic volume in the five experimental groups were statistically significant (P<0.01). Furthermore, there were dose-dependent increases in LV mass and left ventricular end-diastolic volume in PTH-treated rats; however, the differences between any two groups did not reach statistical significance (P>0.05). Immunohistochemical staining and western blot analysis using an anti-PTH polyclonal antibody was performed to evaluate the protein expression levels of PTH in myocardial tissues. The mRNA expression levels of PTH and BNP were measured using reverse transcription-quantitative polymerase chain reaction. The results demonstrated that the mRNA and protein expression levels of PTH in myocardial tissues were significantly decreased in ADR-treated rats compared with the levels in the control group rats. Injection of recombinant PTH significantly increased PTH expression and reduced BNP expression in dose-dependent manners (P<0.05). These findings demonstrated that PTH can improve cardiac function in rats with ADR-induced CM, suggesting a potential therapeutic application for PTH in non-ischemic CM.

[Autologous sinoatrial node cells heterotopic transplantation for treating bradycardia: an experiment with dogs].

OBJECTIVE: To explore the feasibility of autografting sinoatrial nodal cells heterotopic transplantation to construct an ectopia pacemaker for treating bradycardia. METHODS: Sixteen healthy adult dogs were randomly divided into 2 equal groups: graft group and control group. The sinoatrial node (SAN) of the dogs in the graft group was harvested and digested into cell suspension in vitro, then injected to the autogenic right ventricular wall adjacent to heart apex. Commensurable culture medium was injected to the same position with the dogs in control group. Two week later, all dogs underwent transcatheter ablation of His bundle to create a complete heart block model and an electrophysiology study was carried out. In order to investigate the change of rhythm, isoproterenol and atropine was injected respectively to dogs of the graft group. Two weeks later the dogs were killed with their hearts taken out. Immunofluorescence histochemistry was used to investigate the survival of grafted cells and gap junction formed between grafted cells and ventricular myocytes. RESULTS The isolated cells from SAN retained active and beating. After ablation, the heart rate of the dogs of the graft group was (91 +/- 14) bpm, significantly higher than that of the control group, [(49 +/- 11) bpm, t = 6. 672, P < 0.01], and electrocardiography showed that these ventricular rhythms originated from the cell transplant sites. After the injection of isoproterenol the ventricular rate of the graft group was (118 +/- 15) bpm, significantly higher than that before the injection, (95 +/- 11) bpm, t = 3.491, P < 0.01), however, after the injection of atropine, the heart rate of the graft group was (101 +/- 17) bpm, not significantly different from that before the injection, [(95 +/- 11) bpm, t = 0.838, P > 0.05]. Immunofluorescence staining showed that the grafted autografting sinoatrial nodal cells all survived and that there was connexin-43 expression among the cells. CONCLUSION: Transplantation of autologous SAN cells into the right ventricular wall can boost the ventricular rhythm which is sensitive to isoproterenol but not to atropine. Grafted SAN cells can form gap junctions with adjacent myocytes.

Correlation between serum parathyroid hormone levels and coronary artery calcification in patients without renal failure.

The aim of the present study was to investigate the correlation between serum parathyroid hormone (PTH) levels and coronary artery calcification (CAC) in patients without renal failure, as well as to determine independent risk factors of CAC score (CACS). A total of 157 patients who underwent coronary computed tomography angiographic examination at the 101th Hospital of the People's Liberation Army between December 2013 and February 2015 were retrospectively evaluated. The correlation between PTH levels and CACS was determined using a Pearson correlation analysis. A receiver operating characteristic (ROC) curve was drawn to determine the best cutoff PTH level for prediction of CAC. The independent association between serum PTH levels and CAC was analyzed by using a logistic regression analysis model with the response variable Be binary class. The results revealed that PTH levels in patients in the CAC group were significantly higher than those of patients in the non-calcification group. PTH levels were positively correlated with CACS (r=0.288, P<0.001). The ROC curve suggested that a PTH level of ≥31.05 pg/ml was the best cut-off point for the prediction of CAC, with a sensitivity of 80.88%, specificity of 60.67% and an area under the curve of 0.761. After including predictive factors for CAC (gender, age, smoking status, diabetes, hypertension, hyperlipidemia, body mass index, glomerular filtration rate and calcium, phosphorus, calcium-phosphorus product, magnesium, PTH, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol and C-reactive protein levels), the odds ratio of the serum PTH levels regarding the prediction of CAC was 1.050 (95% confidence interval, 1.027-1.074; P<0.001). In conclusion, the present study suggested that serum PTH levels are correlated with CAC in patients without renal failure and may thus be used as a reliable predictor of CAC.

Expression of BMP4 in myocardium and vascular tissue of obese mice.

BACKGROUND: Obesity is regarded as a risk factor for cardiovascular disease. Bone morphogenetic protein 4 (BMP4) is a proinflammatory and profibrotic factor, and the reduced expression of this molecule in obese mice seems to be inconsistent with the known proinflammatory effects of obesity. Therefore, we studied BMP4 expression and inflammation in the myocardial tissue and aortas of obese mice. METHODS AND RESULTS: Four-week-old ob/ob mice were used as the experimental group, and C57BL/6 mice comprised the control group. Animals were sacrificed after a 12-week full diet, and then the blood, heart, abdominal aorta, and inguinal adipose tissue were collected. The expression of BMP4 mRNA and protein in the heart and aorta was significantly higher in the experimental group than in the control group, but expression was lower in adipose tissue. Inflammation measured by the expression of IL-1ß and IL-9 mRNA and protein and Smad1 and phosphorylated Smad1/5/8 protein in the heart and aorta was higher in the experimental group than in the control group. In addition, the expression of BMP4 in the serum was significantly higher in the experimental group than in the control group. CONCLUSION: BMP4 is significantly overexpressed in the myocardial tissue and aortas of obese mice, and mediates local inflammatory responses.

Pan-nitinol occluder and special delivery device for closure of patent ductus arteriosus: a canine-model feasibility study.

The aim of this study was to evaluate a new type of occluder for patent ductus arteriosus. Patent ductus arteriosus was established in a canine model by anastomosing a length of autologous jugular vein to the descending aorta and the left pulmonary artery in an end-to-side fashion. Transcatheter closure of each patent ductus arteriosus was performed on 10 dogs, which were then monitored for as long as 6 months with aortography, echocardiography, and histologic evaluation. Transcatheter closure with use of the novel pan-nitinol device was successful in all canine models. Postoperative echocardiography showed that the location and shape of the occluders were normal, without any residual shunting. Further histologic evaluation confirmed that the occluder surface was completely endothelialized 3 months after implantation. Transcatheter patent ductus arteriosus closure with the pan-nitinol occluder can be performed safely and successfully in a canine model and shows good biological compatibility and low mortality rates.

Changes of plasma B-type natriuretic peptide levels after high-pressure post-dilation following coronary stent deployment.

OBJECTIVE: To evaluate the changes of plasma B-type natriuretic peptide(BNP) levels after high-pressure post-dilation following coronary stent deployment. METHODS: A total of 173 patients undergoing percutaneous coronary intervention for the left anterior descending artery were enrolled into the study. All patients were divided into two groups: the conventional group and the post-dilation group. The plasma BNP, troponin I(TnI), myocardial band isoenzyme of creatine kinase(CK-MB) levels and the serum high sensitive C-reactive protein(hs-CRP) levels immediately before and 24 hours after the interventional procedures were compared between the two groups. RESULTS: There were no significant differences between the two groups in terms of clinical features, clinical and biochemical parameters, stent parameters, pre-procedural plasma BNP and TnI levels, pre-procedural serum hs-CRP levels, as well as pre- and post-procedural CK-MB levels (all P>0.05). In the conventional group, post-procedural plasma BNP levels were significantly reduced when compared with the pre-procedural levels, median(25th,75th) were 32.5 ng/L(15.0,52.4) vs. 37.7 ng/L(18.2,67.3), P = 0.001. In the post-dilation group, post-procedural plasma BNP levels were significantly increased when compared with the pre-procedural levels, median(25th,75th) were 53.5 ng/L(29.6,82.8) vs. 44.2 ng/L(17.15,70.7), P<0.0001. Post-procedural plasma TnI levels were also significantly increased when compared with the pre-procedural levels in both groups, median(25th,75th) were 0.02 ng/L(0.01,0.08) vs. 0.01 ng/L(0.01,0.01), 0.05 ng/L(0.01,0.35) vs. 0.01 ng/L(0.01,0.01), respectively, P<0.0001, so were the serum hs-CRP levels, median(25th,75th) were 3.3 mg/L(2.4,4.7) vs. 2.2 mg/L(1.4,3.3), 4.2 mg/L(3.175,5.825) vs. 2.3 mg/L(1.45,3.6), respectively, P<0.0001. Post-procedural plasma BNP, TnI and serum hs-CRP levels in the post-dilation group were significantly higher than those in the conventional group(all P<0.0001). CONCLUSION: High-pressure post-dilation following coronary stent deployment resulted in a significant increase of plasma BNP levels, as well as plasma TnI levels and serum hs-CRP levels, which may be related to myocardial perfusion, more myocardial injury and more inflammation.

Eighteen-month outcome of pulmonary valve stent implantation by direct right ventricle puncture: an animal study.

OBJECTIVE: The purpose of this study was to investigate the feasibility and safety of pulmonary valve implantation via direct right ventricle puncture. METHODS: A standard thoracotomy and direct right ventricle puncture were performed in 8 healthy sheep to implant the pulmonary valve stents. Animals were followed up for 18 months. RESULTS: Three sheep died within the first 4 months after stent placement. The remaining 5 animals survived. After 18 months, examinations by color echocardiography, 64-slice computed tomography scan, and cardiac catheter showed an ideal position of each stent. The function of the pulmonary valves and hearts was not different compared with the preoperative conditions of the sheep. Anatomic examination revealed that the stent was covered by a layer of endothelial tissue with no stent fracture or valvular calcification. The histologic evaluation of the stent and surrounding tissue showed that the surface of the stent was smooth and covered by a complete layer of endothelial cells without obvious infiltration of inflammatory cells. The vascular wall was integrative without tear phenomenon in each layer of tissue. CONCLUSIONS: These results show that pulmonary valve stents can be implanted via direct right ventricle puncture. Further studies evaluating xenograft valve material and the effect of implantation in vivo are needed.

Percutaneous valve stent insertion to correct the pulmonary regurgitation: an animal feasibility study.

BACKGROUND: Pulmonary regurgitation leads to progressive right ventricular dysfunction, susceptibility to arrhythmias, and sudden cardiac death. Percutaneous valve replacement has been developed in recent years, providing patients with an alternative option. Percutaneous pulmonary valve replacement has been recently introduced into clinical practice. The goal of this study was to evaluate the feasibility of percutaneous valve stent insertion to correct the pulmonary regurgitation in sheep using a cup-shaped valve stent. METHODS: Pulmonary regurgitation was created by percutaneous cylindrical stent insertion in native pulmonary annulus of 8 sheep. One month after the initial procedure, the sheep with previous cylindrical stent implanted underwent the same implantation procedure of pulmonary valve stent. The valve stent consisted of a cup-shaped stent and pericardial valves. Hemodynamic assessments of the bioprosthetic pulmonary valve were obtained by echocardiography at immediately post-implant and at 2 months follow up. RESULTS: Successful transcatheter cylindrical stent insertion was performed in 7 sheep but failed in 1 sheep because the cylindrical stent was released to right ventricle outflow tract. After one month the 7 sheep with pulmonary regurgitation underwent valve stent implantation successfully. Echocardiography confirmed the stents were in desired position during the follow-up. No evidence of pulmonary valve insufficiency occurred in any animals. Echocardiography showed all heart function markers were normal. CONCLUSIONS: Percutaneous cylindrical stent insertion to induce significant pulmonary regurgitation in sheep was feasible, simple and reproducible. Percutaneous pulmonary valve stent implantation can reduce pulmonary regurgitation in a sheep model. Further development of animal model and clinical trials are warranted.

Percutaneous establishment of tricuspid regurgitation: an experimental model for transcatheter tricuspid valve replacement.

BACKGROUND: Valve replacement or repair is recommended in patients with tricuspid regurgitation when deterioration of their clinical status occurs as a consequence of right ventricular dysfunction. Percutaneous valve replacement was developed in recent years. To investigate the feasibility, effectiveness and long-term results of percutaneous tricuspid valve replacement, an experimental model with tricuspid regurgitation is needed. We developed a simple and reproducible percutaneous approach for the creation of tricuspid regurgitation in sheep. METHODS: A specially designed grasping forceps were used to grasp chordae tendineae or the tricuspid valve leaflets through a catheter. Transcatheter creation of tricuspid regurgitation was performed on 7 healthy sheep. These sheep were followed up shortly after the procedure and at 6th month post-procedure with echocardiography. Additionally, all the sheep were sacrificed for anatomic evaluation at 6th month after the procedure. RESULTS: Creation of tricuspid regurgitation was successfully accomplished in all sheep. Necropsy confirmed that damage was done to the tricuspid valve apparatus in all animals (tearing of the anterior leaflet of the tricuspid valve in five animals and posterior leaflet of the tricuspid valve in two animals). At the six-month follow-up, there was no significant increase in the right ventricle dimension and ejection fraction measured by echocardiography. Autopsy examinations demonstrated the tearing of tricuspid valve leaflets. CONCLUSIONS: The creation of an animal model of tricuspid regurgitation via a percutaneous approach using forceps to sever one or more tricuspid leaflets is feasible and will allow investigation of devices designed replace the tricuspid valve via a percutaneous approach. Despite significant tricuspid regurgitation, the hemodynamics did not change during the follow-up period in this model.

Use of a novel valve stent for transcatheter pulmonary valve replacement: an animal study.

OBJECTIVE: The goal of this study was to evaluate valvular functionality after transcatheter pulmonary valve replacement in sheep using a novel pulmonary valve stent. METHODS: Fresh porcine pericardium cross-linked with 0.6% glutaraldehyde was treated with L-glutamine to eliminate glutaraldehyde toxicity and sutured onto a valve ring before mounting on a nitinol stent to construct the pulmonary valve stent. Percutaneous femoral vein transcatheter pulmonary valve replacement was performed with the newly constructed valve stent. Pulmonary valve stents were implanted in 10 healthy sheep (6 males and 4 females) weighing an average of 25.7 +/- 4.1 kg. Color Doppler echocardiography, 64-row computed tomography, and direct catheter examination were used to assess valvular function. RESULTS: Implantation was successful in 8 sheep. Shortly after surgery, all artificial valve stents exhibited normal open and close functionality and no stenosis or insufficiency. Heart rate was slightly elevated at this time, while all other hemodynamic parameters were normal. Six-month follow-up revealed no evidence of valve stent dislocation and normal valvular and cardiac functionality. There was no evidence of stent fracture. Repeated valve stent implantation was well tolerated as indicated by good valvular functionality 2 months postdelivery. CONCLUSION: The novel pulmonary valve stent described herein can be delivered via percutaneous femoral vein transcatheter implantation and is highly efficacious at 6 months postdelivery. Furthermore, repeated valve stent replacement was successful.