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Han J.,Wannan Medical College | He G.-W.,Hangzhou Normal University | He G.-W.,TEDA International Cardiovascular Hospital | He G.-W.,Oregon Health And Science University | Chen Z.-W.,Anhui Medical University
Evidence-based Complementary and Alternative Medicine | Year: 2014

We for the first time investigated the effect and mechanism of the total flavones of Rhododendron simsii Planch (TFR), a widely-used Chinese herb for a thousand years, on vasodilatation and hyperpolarization in middle cerebral artery (MCA) of rats subject to global cerebral ischemia-reperfusion (CIR). TFR (112700 mg/L) evoked dose-dependent vasodilation and hyperpolarization in MCA of both sham and CIR that were partially inhibited by 30 M N-nitro-L-arginine- methyl-ester and 10 M indomethacin and further attenuated by endogenous H 2S synthese-CSE inhibitor PPG (100 M) or Ca2+-activated potassium channel (K ca) inhibitor TEA (1 mM). In whole-cell patch clamp recording, TFR remarkably enhanced the outward current that was inhibited by TEA. CIR increased CSE mRNA expression and the contents of H2S that were further increased by TFR. We conclude that, in MCA of CIR rats, TFR induces non-NO and non-PGI2-mediated effects of vasodilatation and hyperpolarization involving K ca and increases CSE mRNA expression level in endothelial cells and H2S content in the cerebrum. These findings suggest that the response induced by TFR is potentially related to endothelium-derived hyperpolarizing factor mediated by the endogenous H 2S and promote the use of TFR in protection of brain from ischemia-reperfusion injury. © 2014 Jun Han et al.


He G.-W.,TEDA International Cardiovascular Hospital | He G.-W.,Hangzhou Normal University | He G.-W.,Oregon Health And Science University | Taggart D.P.,University of Oxford
Annals of Thoracic Surgery | Year: 2016

Spasm of arterial grafts in coronary artery bypass grafting surgery is still a clinical problem, and refractory spasm can occasionally be lethal. Perioperative spasm in bypass grafts and coronary arteries has been reported in 0.43% of all coronary artery bypass grafting surgery, but this may be an underestimate. Spasm can develop not only in the internal mammary artery but more frequently in the right gastroepiploic and radial artery. The mechanism of spasm can involve many pathways, particularly those involving regulation of the intracellular calcium concentration. Endothelial dysfunction also plays a role in spasm. Depending on the clinical scenario, the possibility of spasm during and after coronary artery bypass grafting should be confirmed by angiography. If present, immediate intraluminal injection of vasodilators is often effective, although other procedures such as an intraaortic balloon pump or extracorporeal membrane oxygenation may also become necessary to salvage the patient. Prevention of spasm involves many considerations, and the principles are discussed in this review article. © 2016 The Society of Thoracic Surgeons.


Huang J.-H.,Chinese University of Hong Kong | Huang J.-H.,Nankai University | He G.-W.,Oregon Health And Science University | Xue H.-M.,Chinese University of Hong Kong | And 6 more authors.
Cardiovascular Research | Year: 2011

Aims Intracellular Ca 2+ ([Ca 2+]i) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxiareoxygenation (HR) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that HR may reduce TRPC3 activity and the associated endothelial function, including NO release. Methods and results Measurements of [Ca 2+]i and patch-clamp study in primary cultured porcine coronary endothelial cells, measurements of NO and endothelium-dependent relaxation in porcine coronary arteries, and RT-PCR and western blot were conducted. Pre-treatment with SKF96365 (an inhibitor of TRPCs) or the selective TRPC3 inhibitor Pyr3 significantly decreased bradykinin-induced vasorelaxation. One hour of hypoxia followed by reoxygenation significantly reduced the vasorelaxation (70.3 ± 6.4 vs. 88.9 ± 3.5) and NO concentration (24.0 ± 1.3 vs. 45.2 ± 2.8 nmol/L), and they were restored by pre-incubation with the TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (96.4 ± 1.8 and 41.1 ± 4.7 nmol/L, respectively). In porcine coronary endothelial cells, HR inhibited bradykinin-activated membrane current (8.6 ± 0.4 vs. 14.0 ± 1.5 pA/pF) and Pyr3-sensitive TRPC3 current (3.8 ± 0.3 vs. 6.3 ± 0.6 pA/pF; P< 0.01). HR also inhibited bradykinin-induced Ca 2+ influx and the Ca 2+ influx via TRPC3. Cell surface expression of TRPC3 was decreased after HR. Conclusions We have, for the first time, demonstrated that Ca 2+ entry via endothelial TRPC3 contributes to NO release and have revealed that HR is associated with inhibition of TRPC3 activity. Inhibition of channel trafficking to the cell surface is involved in the underlying mechanism of the decrease of TRPC3 current and the reduction in Ca 2+ entry through TRPC3 during HR. This study suggests that TRPC3 may have the potential to be a new target for endothelial protection during HR. © The Author 2011.


Tu S.,Leiden University | Barbato E.,Onze Lieve Vrouwziekenhuis OLV Hospital | Koszegi Z.,Josa Andras Teaching Hospital | Yang J.,Guangdong General Hospital | And 7 more authors.
JACC: Cardiovascular Interventions | Year: 2014

Objectives This study sought to present a novel computer model for fast computation of myocardial fractional flow reserve (FFR) and to evaluate it in patients with intermediate coronary stenoses. Background FFR is an indispensable tool to identify individual coronary stenoses causing ischemia. Calculation of FFR from x-ray angiographic data may increase the utility of FFR assessment. Methods Consecutive patients with intermediate coronary stenoses undergoing pressure wire-based FFR measurements were analyzed by a core laboratory. Three-dimensional quantitative coronary angiography (QCA) was performed and the mean volumetric flow rate at hyperemia was calculated using TIMI (Thrombolysis In Myocardial Infarction) frame count combined with 3-dimensional QCA. Computational fluid dynamics was applied subsequently with a novel strategy for the computation of FFR. Diagnostic performance of the computed FFR (FFR QCA) was assessed using wire-based FFR as reference standard. Results Computation of FFRQCA was performed on 77 vessels in 68 patients. Average diameter stenosis was 46.6 ± 7.3%. FFRQCA correlated well with FFR (r = 0.81, p < 0.001), with a mean difference of 0.00 ± 0.06 (p = 0.541). Applying the FFR cutoff value of ≤0.8 to FFR QCA resulted in 18 true positives, 50 true negatives, 4 false positives, and 5 false negatives. The area under the receiver-operating characteristic curve was 0.93 for FFR QCA, 0.73 for minimum lumen area, and 0.65 for percent diameter stenosis. Conclusions Computation of FFR QCA is a novel method that allows the assessment of the functional significance of intermediate stenosis. It may emerge as a safe, efficient, and cost-reducing tool for evaluation of coronary stenosis severity during diagnostic angiography. © 2014 by the American College of Cardiology Foundation.


De Kam P.-J.,Neuros | Hou J.,TEDA International Cardiovascular Hospital | Wang Z.,MSDBeijing | Lin W.H.,Merck And Co. | Van Den Heuvel M.,MSD
International Journal of Clinical Pharmacology and Therapeutics | Year: 2015

Objective: Elimination of sugammadex occurs predominantly via the kidneys, with the majority of the drug excreted unchanged in the urine. To date, most studies with sugammadex have been performed in non-Asian populations. The objectives of this open-label study were to determine the pharmacokinetics (PK) and safety of single-dose sugammadex (16 mg/kg) in healthy Chinese adult volunteers. Methods: 12 Chinese subjects (6 male; 6 female) received intravenous sugammadex (16 mg/kg) as a 10-second bolus infusion. Blood samples were collected pre-sugammadex and at regular intervals up to 24 hours post-sugammadex for PK assessment. Safety was assessed via AEs, vital signs, electrocardiogram, and laboratory parameters. Results: Following sugammadex 16 mg/kg infusion, peak sugammadex concentration was 197 μg/mL, clearance was 99.7 mL/min, and apparent volume of distribution at equilibrium was 10.5 L. Plasma sugammadex concentrations showed a polyexponential decline over time, with an overall geometric mean (CV%) terminal half-life of 145 minutes (17.9%) (139 minutes (17.7%) for males; 152 minutes (18.6%) for females). No influence of gender on the PK of sugammadex was observed. Three subjects experienced an adverse events (AE) (dysgeusia of mild intensity), which was considered possibly or probably related to sugammadex. There were no clinically significant changes in vital signs, electrocardiography or laboratory parameters. Conclusion: PK of sugammadex (16 mg/kg) was characterized in healthy Chinese subjects. Overall between-subject variability on clearance and apparent volume of distribution was ∼ 10%. Sugammadex was generally well tolerated. ©2015 Dustri-Verlag Dr. K. Feistle.


Zhang L.R.,TEDA International Cardiovascular Hospital
Zhonghua xin xue guan bing za zhi | Year: 2011

To observe the coronary vessel lumen diameter and bifurcation angle in subjects with normal CT coronary angiography (CTCA) imaging. 64-row CT coronary angiography imaging from 526 adult people with excellent image quality and normal vascular image were analyzed in this study. The lumen diameter from the origin to distal with 2 mm lumen of left main coronary artery (LM), anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA) was measured at 1 cm interval in CPR image. The vascular tapered ratio was calculated. The bifurcation angle in the diagonal branch, obtuse marginal branch, posterior descending branch, acute marginal branch as well as the origin diameter was also measured in VR image. The LAD average length was 13 cm and lumen diameter was 3.92 mm at origin and 2.10 mm at distal. The average decremented ratio of LAD was 7.7% (male 7.0%, female 8.4%). The maximal decremented ratio 8.0% - 10.0% occurred at 3 - 5 cm apart from the origin of LAD. The LCX average length was 13 cm and lumen diameter was 3.57 mm at origin and 2.10 mm at distal. The average decremented ratio of LCX was 9.7% (male 9.6%, female 9.7%). Lumen decremented ratio was less than 3.0% between origin and proximal 3 cm and 8.3% - 10.7% in the rest portion of the LCX. The RCA average length was 18 cm and lumen diameter was 3.97 mm at origin and 2.15 mm at distal. The average decremented ratio of RCA was 5.1% (male 4.9%, female 5.3%). The decremented ratio of RCR was less than 4.0% between origin and proximal 10 cm and 6.1% - 15.2% in the rest portion. The bifurcation angle was 50, 55, 66 and 76 degree for LAD with diagonal branch, LCX with obtuse marginal branch, RCA with posterior descending branch and RCA with obtuse marginal branch respectively. Coronary artery length, lumen diameter and decremented ratio as well as bifurcation angel could be identified in 64 row CTCA image in vivo. This information could help us to understand the in vivo coronary artery anatomy.


Chen J.,Tianjin Medical University | Sun F.,Tianjin Medical University | Fu J.,Wuhan Medical Care Center for Women and Children | Zhang H.,Teda International Cardiovascular Hospital
Pediatric Cardiology | Year: 2015

As a transcription factor mainly expressed in cardiovascular system, T-box 20 (TBX20) plays an important role in embryonic cardiovascular system development and adult heart function. Previous studies have identified associations of two SNPs in the T-box DNA-binding domain of TBX20 with congenital heart disease (CHD) in two Caucasian families, but the associations of TBX20 mutations underlying the more common populations with CHD remain to be uncovered. In this study, 25 unrelated Chinese Han neonates with CHD and 25 healthy children as controls were investigated for TBX20 mutations. SNP genotyping was performed by PCR-DNA sequencing. The selected SNPs were well genotyped and SNP rs3999941 was found to be strongly associated with CHD (p = 0.007). The minor allele of rs3999941 showed a high-risk factor for CHD (OR 4.24; 95 % CI 1.41–12.71). Besides, we found a new SNP site located at the 657th nucleotide of the exon 5 of TBX20 gene which may also be associated with CHD, c.657A>C. The frequency was significantly different between two groups (p = 0.011), the minor allele of SNP c.657A>C also showed a risk factor for CHD (OR 2.56; 95 % CI 1.02–6.46). These findings suggested that the TC genotype of SNP rs3999941 and AC genotype of the new SNP c.657A>C in the TBX20 gene may be risk factors for CHD and thus screening of these SNPs may have some implications in the prevention and treatment of CHD in Han Chinese children. © 2014, Springer Science+Business Media New York.


Wang X.-C.,Chinese University of Hong Kong | Sun W.-T.,Chinese University of Hong Kong | Yu C.-M.,Chinese University of Hong Kong | Pun S.-H.,Chinese University of Hong Kong | And 4 more authors.
Atherosclerosis | Year: 2015

Objective: It remains incompletely understood how homocysteine impairs endothelial function. Whether mechanisms such as calcium-activated potassium (KCa) channels are involved is uncertain and the significance of endoplasmic reticulum (ER) stress in KCa channel-dependent endothelial function in hyperhomocysteinemia remains unexplored. We investigated the effect of homocysteine on endothelial KCa channels in coronary vasculature with further exploration of the role of ER stress. Methods: Vasorelaxation mediated by intermediate- and small-conductance KCa (IKCa and SKCa) channels was studied in porcine coronary arteries in a myograph. IKCa and SKCa channel currents were recorded by whole-cell patch-clamp in coronary endothelial cells. Protein levels of endothelial IKCa and SKCa channels were determined for both whole-cell and surface expressions. Results: Homocysteine impaired bradykinin-induced IKCa and SKCa-dependent EDHF-type relaxation and attenuated the vasorelaxant response to the channel activator. IKCa and SKCa currents were suppressed by homocysteine. Inhibition of ER stress during homocysteine exposure enhanced IKCa and SKCa currents, associated with improved EDHF-type response and channel activator-induced relaxation. Homocysteine did not alter whole-cell protein levels of IKCa and SKCa whereas lowered surface expressions of these channels, which were restored by ER stress inhibition. Conclusions: Homocysteine induces endothelial dysfunction through a mechanism involving ER stress-mediated suppression of IKCa and SKCa channels. Inhibition of cell surface expression of these channels by ER stress is, at least partially, responsible for the suppressive effect of homocysteine on the channel function. This study provides new mechanistic insights into homocysteine-induced endothelial dysfunction and advances our knowledge of the significance of ER stress in vascular disorders. © 2015 The Authors. Published by Elsevier Ireland Ltd.


Patent
China Aerospace Science, Technology Corporation and Teda International Cardiovascular Hospital | Date: 2016-08-10

The invention discloses a blood pump control system comprising: a local processing terminal and a remote processing terminal; wherein the local processing terminal is configured to transmit to the remote processing terminal, collected current state parameters of the blood pump and heart activity indexes, and to drive and control the blood pump according to blood pump adjusting parameters received from the remote processing terminal; and wherein the remote processing terminal is configured to obtain current blood pump adjusting parameters according to the current state parameters, and the heart activity indexes received from the local processing terminal, and set adjusting conditions; and to transmit the blood pump adjusting parameters back to the local processing terminal. The problem that closed-loop adjustment of blood pump operating parameters directed to real-time physiological conditions of the carrier is impossible in the prior art is solved, such that the blood pump is more suitable for the use of the carrier, and the heart chamber assisting effect and reliability and safety of the blood pump are improved. The invention also provides a blood pump control method and a blood pump system comprising the control system.


Patent
China Aerospace Science, Technology Corporation and Teda International Cardiovascular Hospital | Date: 2013-11-27

A blood pump control system includes a local processing terminal and a remote processing terminal. The local processing terminal is configured to transmit to the remote processing terminal, collected current state parameters of the blood pump and heart activity indexes, and to drive and control the blood pump according to blood pump adjusting parameters received from the remote processing terminal. The remote processing terminal is configured to obtain current blood pump adjusting parameters according to the current state parameters, and the heart activity indexes received from the local processing terminal, and set adjusting conditions; and to transmit the blood pump adjusting parameters back to the local processing terminal.

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