Bradykinin-(1-9) mitigates autophagy through upregulating PI3K/Akt in rats with myocardial infarction.

The cardioprotective mechanisms of bradykinin-(1-9) in myocardial infarction were unclear. We investigated the effect of bradykinin-(1-9) on cardiac function, fibrosis, and autophagy induced by myocardial infarction and identified the mechanisms involved. To investigate the cardioprotective effect of bradykinin-(1-9), various doses of bradykinin-(1-9), its B2 receptor blocker HOE140, or their combination were administered to rats via subcutaneous osmotic minipump implantation before myocardial infarction. After 2 days, myocardial infarction was induced by ligation of the left anterior descending coronary artery. After 2 weeks, echocardiographic measurements and euthanasia were performed. Bradykinin-(1-9) treatment attenuated left ventricular dysfunction, fibrosis, and autophagy in rats with myocardial infarction, which was partially reversed by HOE140 administration. Moreover, the downregulatory effect of bradykinin-(1-9) on autophagy was partially reversed by combination with the PI3K inhibitor LY294002. Thus, bradykinin-(1-9) inhibits myocardial infarction-induced cardiomyocyte autophagy by upregulating the PI3K/Akt pathway.

Hypernatremia induced by low-dose Tolvaptan in a Patient with refractory heart failure: A case report.

RATIONALE: Tolvaptan (TLV) is a selective vasopressin type 2 receptor antagonist, which has an active effect on patients with congestive heart failure especially combined with hyponatremia. Increasingly, evidence has demonstrated that low-dose tolvaptan can dramatically relieve patients' dyspnea and the dose would not cause severe electrolyte abnormalities. Even hypernatremia is a major adverse effect of tolvaptan, treatment with tolvaptan shows good security and is well-tolerated. Few cases have reported that patients who developed severe hypernatremia induced by low-dose Tolvaptan. PATIENT CONCERNS: A 68-year-old man was admitted to our hospital with dyspea and general fatigue. He was diagnosed with acute decompensated heart failure due to ischemic cardiomyopathy. In order to improve fluid retention and relieve his dyspnea, low-dose TLV (7.5 mg qd) was performed. After the 3-day treatment using TLV, we observed that he became delirious and his limbs shook uncontrollably. High serum sodium 173 mmol/L was noted compared to the results of the first examination (137 mmol/L). After intensive rescue, serum sodium was restored to normal (135 mol/L). Later, when the patient refused continuous renal replacement therapy (CRRT), we tried again to use a lower dose of TLV to improve diuretic resistance. Two days later, Serum sodium rose again (162 mmol/L). DIAGNOSES: During the course of therapy, we did not strictly require the patient to control the fluid intake. No other medication could cause elevation of serum sodium. Therefore, we suspected a high sensitivity to the side effect of TLV. INTERVENTION: Stop the use of TLV and encourage the patient to drink plenty of water. Gastric tube was inserted orally to increase the intake of fresh water. OUTCOMES: His serum sodium decreased gradually and his psychiatric symptom recovered. During this period, Overall condition of the patient was stable. After being discharged from the hospital, the patient eventually died of cardiac arrest due to critically ill heart failure. LESSONS: Hypernatremia is a severe side effect of TLV. For critical patients, TLV should be used at a low dose and electrolyte should be detected in time.

Acellular Spinal Cord Scaffold Implantation Promotes Vascular Remodeling with Sustained Delivery of VEGF in a Rat Spinal Cord Hemisection Model.

BACKGROUND: Promoting angiogenesis provides a possible therapeutic approach in treating spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a pro-angiogenic substance that is involved in endothelial cell (EC) proliferation, migration, and survival. Exogenous administration of VEGF to the lesion epicenter of the spinal cord has been recently revealed as a potential method for promoting the blood vessel sprouting. METHODS: Spinal cord hemisection in a rat model was established and angiogenesis was studied through implant of an acellular spinal cord scaffold (ASCS) with sustained delivery of VEGF₁₆₅. The poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating VEGF₁₆₅ were fabricated on basis of an emulsion and solvent evaporation method and conjugated to ASCS by a Genipin (GP) crosslinking technology. The resultant scaffolds were marked as V-ASCS. VEGF₁₆₅ entrapment efficiency (EE) and released kinetics were determined by an ultraviolet absorption measurement. Angiogenesis and vascular remodeling were observed via a high-resolution micro-CT and analyzed quantitatively by vascular morphometric parameters. Spinal cord histology and Basso, Beattie, and Bresnahan (BBB) locomotor rating scale were further studied. RESULTS: VEGF₁₆₅ was entrapped with high efficiency (90.8±3.1) %. In vitro VEGF₁₆₅ release kinetics study showed an initial burst of 1.966 µg mg NPs-1 and 1.045µg mg V-ASCS-1 respectively in the first 24 hours. In the phase of sustained release, approximately 0.040µg mg NPs-1 and 0.022µg mg V-ASCS-1 per day was on-going until 720h. In the rat spinal cord hemisection model, implant of V-ASCS at the injured site showed a promotion of angiogenesis and vascular remodeling following SCI. A better outcome can be confirmed histologically. However, functional improvement is limited in the animal model. CONCLUSION: The results indicate that progress of vascular reconstruction is accelerated in the V-ASCS implanted SCI rats.

Feasibility and safety of transthoracic echocardiography-guided transcatheter closure of atrial septal defects with deficient superior-anterior rims.

Although previous studies showed that transthoracic echocardiography (TTE) can be used to guide transcatheter closure of atrial septal defect (ASD), whether TTE can be used to guide transcatheter closure of secundum ASD with a deficient superior-anterior rim is unknown and this critical issue was addressed in the present study. A total of 280 patients with secundum ASD who underwent transcatheter ASD closure were recruited and divided into groups A and B depending on ASD superior-anterior rim>4 mm (n = 118) or ≤4 mm (n = 162). TTE was used to guide Amplatzer-type septal occluder (ASO) positioning and assess residual shunt. Procedure success was defined as no, trivial and small residual shunt immediately after the procedure as assessed by color Doppler flow imaging. Group A and group B did not differ in complication rate (8.55% vs.7.55%), procedure success rate (98.3% vs. 95.0%) or complete closure rate immediately after the procedure (89.7% vs. 89.3%) or at 6-month follow-up (98.3% vs. 96.8%). The mean procedure and fluoroscopy time in group B were much longer than those in group A. In conclusion, the absence of a sufficient superior-anterior rim in patients undergoing percutaneous closure of secundum-type ASDs using fluoroscopic and TTE guidance is associated with slightly greater device malposition and migration as well as increased procedural and fluoroscopic times, but the overall complication rate did not differ with TTE guidance when compared to historical controls that used TEE guidance.

[Methods on construction of core germplasm collection of Scutellaria baicalensis by ISSR marker].

OBJECTIVE: To build up primary core germplasm of Scutellaria baicalensis. METHODS: The genetic diversity of 40 germplasm resources of Scutellaria baicalensis in different province were analyzed by ISSR, and the primary core germplasm were constructed with progressive sampling method of smallest genetic distance. RESULTS: 15 primers, which showed good repetitive, special bands and distinct polymorphism, were selected from 51 random ISSR primers. Then the total 248 loci were amplified by these selected 15 primers, with a 97.17% polymorphic loci. The average of Shannon information index (I), Nei's genetic diversity (H), number of alleles and effective number of alleles (NE) by POPGENE 32 analysis were 0.4353, 0.2819, 1.9640 and 1.4617, respectively. It showed there was highly genetic diversity in the 40 germplasm resources. The result of analysis by NTSYS-PC software shows the genetic similarity (Gs) were among 0.64 and 0.80, and there was upper coherence between the clustering result and source core germplasm collection except individual germplasms. The result showed the percentage of polymorphic loci was obviously reduced and the Shannon's information index and Nei's genetic diversity were increased a little, but the index change of germplasm genetic diversity was less than that before sampling. The core germplasms from No. 3 sampling were most representative, whose sampling number was about 30% of the initial sampling, and the percentage of polymorphic loci was that of before sampling 96.8%. CONCLUSIONS: It was practicable that the methods would be used to construct core germplasm collection of Scutellaria baicalensis by ISSR marker.

Safety and efficacy of transcatheter closure of atrial septal defects guided by transthoracic echocardiography: a prospective study from two Chinese Medical Centers.

The purpose of this study was to evaluate the safety and efficacy of transcatheter atrial septal defect (ASD) closure guided by transthoracic echocardiography (TTE). A total of 191 patients with ASD were recruited from two Chinese medical centers and TTE was carefully performed in multiple views to observe ASD number, position, diameter and relation with adjacent cardiac structures. All patients were divided into three groups based on their largest ASD diameters: 66 subjects with ASD diameter 5-14 mm (group A); 60 subjects with ASD diameter 15-20 mm (group B); and 65 subjects with ASD diameter 21-38 mm (group C). Atrial septal occluders (ASOs) were successfully deployed in 188 patients (98.4%) and ASD was successfully closed at 6-mo follow-up in 185 patients (96.9%). The difference between diameters of ASO and ASD (ASO-ASD) in groups A, B and C were 3.9 +/- 2.4 (0-7) mm, 5.0 +/- 2.6 (3-8) mm and 6.2 +/- 3.8 (5-11) mm, respectively. In group A, no complications occurred. In group B, only four patients had mild complications such as sinus bradycardia, transient hematuria and migraine, all of which disappeared after treatment. In group C, one patient developed ASO migration into the right atrium and two patients had their ASO migrated into the right ventricular outflow tract. Immediately after the closure, 60 (90.9%), 53 (88.3%) and 53 (82.8%) patients had complete ASD closure; 2, 4 and 6 patients had trivial residual shunts; 4, 3 and 2 patients had small residual shunts; and 0, 0 and 2 patients had moderate residual shunts in groups A, B and C, respectively. Most of the residual shunts were persistent at 6-mo follow-up. No embolism or death at procedure and 6-mo follow-up occurred. In conclusion, TTE is a reliable technique for measurement of ASD diameter, guidance of transcatheter ASD closure and evaluation of residual shunts. Transcatheter ASD closure guided by TTE is safe and effective, especially in patients with ASD

Reliability of transthoracic echocardiography in estimating the size of Amplatzer septal occluder and guiding percutaneous closure of atrial septal defects.

BACKGROUND: In China, transthoracic echocardiography (TTE) is popularly used for pre-intervention examination for atrial septal defect (ASD) and for guiding ASD closure. However, the ability to determine ASD size and the safety and efficacy of TTE for guiding ASD closure still has not been widely accepted. This study aimed to evaluate the efficacy and safety of TTE used before, during and after transcatheter ASD closure with Amplatzer septal occluders (ASO). METHODS: Sixty-eight subjects (15 men and 53 women; mean age (33.7 +/- 17.3) years) were enrolled. TTE was used to measure the diameters and guide transcatheter closure of ASD. The ASD was examined by long-axis view, basal short-axis view, apical four-chamber view and the subcostal view to observe position, diameter and relation with neighbouring structures. The largest diameter was selected as the reference diameter. Patients were divided into 3 groups according to the ASD reference diameter: 22 subjects with ASD diameter 4 - 14 mm (group A); 21 subjects with ASD diameter 15 - 20 mm (group B); and 25 subjects with ASD diameter 21 - 33 mm (group C). RESULTS: ASD was occluded successfully in groups A and B. In group C, occlusion failed in 2 cases; 1 case remained with a 3-mm residual shunt sustained until 6-month follow-up. However, at 6-month follow-up, no case of thromboembolism, ASO dislocation or death occurred in the three groups. The diameter of ASD measured by TTE could accurately predict the ASO size that could successfully occlude the ASD, especially in patients with ASD < 20 mm. The ASD diameter measured by TTE correlated well with ASO size (r = 0.925, P < 0.001; r = 0.976, P < 0.001; r = 0.929, P < 0.001 respectively). CONCLUSIONS: ASD diameter measured by TTE can accurately estimate the size of the ASO needed for successful closure of ASD. The larger the ASD, the much larger the ASO needed. TTE is a satisfactory guiding imaging tool for ASD closure.

Multivessel percutaneous coronary intervention in Chinese patients with acute myocardial infarction and simple nonculprit arteries.

BACKGROUND: Multivessel percutaneous coronary intervention (PCI) for patients during acute myocardial infarction (AMI) is currently controversial. In this study, we investigated the significance of multivessel PCI in Chinese patients with ST-segment elevation AMI and relatively simple lesions in nonculprit arteries. METHODS: We reviewed all consecutive primary PCI of ST-segment elevation AMI in our hospital between 2002 and 2005. The patients with multivessel disease and ACC/AHA type A/B1 lesions in nonculprit arteries who underwent multivessel PCI were identified (n = 105, multivessel PCI group), and 120 patients with single-vessel disease and treatment with primary PCI were enrolled as control subjects (single-vessel PCI group). The primary end points were the occurrences of 6-month major adverse cardiac events (cardiogenic death, nonfatal reinfarction, and target vessel revascularization). The secondary end points included procedure time, angiographic success rate, TIMI grade, reperfusion arrhythmia, ST-segment resolution, and left ventricular ejection fraction. RESULTS: All patients with multivessel PCI tolerated the operations well and had similar TIMI 3 and angiographic success rates but longer procedure times than those patients with single-vessel PCI. There were no significant differences in reperfusion arrhythmia, ST-segment resolution, left ventricular ejection fraction, or 6-month MACEs between both groups. CONCLUSIONS: This study suggests that multivessel PCI is effective and safe for Chinese patients with ST-segment elevation AMI and simple lesions in nonculprit arteries.

Facilitated PCI in younger Chinese patients with AMI.

Presently, facilitated percutaneous coronary intervention (PCI) in patients remains controversial. We evaluated the efficacy and safety of facilitated PCI, intravenous low-dose rt-PA administration prior to urgent PCI, in Chinese patients < 70 years of age with ST-segment elevation myocardial infarction. Our results suggest that the age and dosage of thrombolytics should be noticed seriously when considering facilitated PCI.

[The role of atherosclerotic plaque stability and inflammation in the pathogenesis of acute coronary syndrome].

OBJECTIVE: To elucidate the effect of inflammation and coronary atherosclerotic plaque destabilization in the pathogenesis of acute coronary syndromes (ACS). METHODS: Twenty-eight patients with ACS and 13 patients with stable angina pectoris (SA) were examined by intravascular ultrasound (IVUS). Coronary plaque morphology and areas in culprit lesions were analyzed. The serum levels of hs-CRP, MMP-9, TIMP-1, sCD40L were also measured. RESULTS: Soft plaques were dominant in culprit lesions of ACS patients (71.4%, 20/28), and hard plaques were dominant in culprit lesions of SA patients [76.9% (10/13), P = 0.004]. At the culprit site, plaque area, plaque burden and remodeling index were all significantly larger in culprit lesions of ACS patients than those of SA patients (all P < 0.05). Positive remodeling was more frequent in ACS patients than in SA patients, whereas negative remodeling was more frequent in SA patients (P < 0.05). The serum levels of hs-CRP, MMP-9, sCD40L were higher in ACS group compared with SA group (P < 0.05, respectively). Moreover, hs-CRP level was positively correlated with MMP-9 (r = 0.671, P = 0.000) and sCD40L (r = 0.494, P = 0.008), respectively, in ACS patients. There was no difference in TIMP-1 between two groups (P = 0.234). CONCLUSIONS: These results suggest that structurally vulnerable plaques are essential element in the pathogenesis of ACS and inflammation might play an important role in plaque vulnerability.

[Changes of neutrophil myeloperoxidase in coronary circulation among patients with acute coronary syndrome].

OBJECTIVE: To investigate the changes of neutrophil myeloperoxidase (MPO) blood concentration gradient between the systemic circulation and the coronary circulation among patients with acute coronary syndrome and its clinical value. METHODS: Fifty patients underwent coronary angiography, which including 10 patients in AMI group, 20 patients in UA group, 10 patients in SA group and 10 subjects served as control. The levels of MPO and hs-CRP were measured in the serum of blood collected from femoral vein, aortic artery root and coronary sinus. RESULTS: Compared with the control, concentrations of LDL in the AMI, UA and SA groups were significantly increased, while the latter three groups did not differ from each other. In the UA patients, the in-gate percentage of MPO decreased in the coronary sinus compared with that in the root of aortic artery (P < 0.01); the in-gate percentage of MPO decreased through coronary circulation more than through systemic circulation (P < 0.001); the average fluorescent intensity of MPO and the concentrations of hs-CRP showed no difference between samples from the coronary sinus and that from the root of aortic artery. In the AMI patients, the average fluorescent intensity of MPO in the coronary sinus was weakened compared with that in the root of aortic artery (P < 0.05); it decreased through coronary circulation more than through systemic circulation (P < 0.001); neither the in-gate percentage of MPO nor the concentrations of hs-CRP showed significant difference between samples from the coronary sinus and that from the root of aortic artery. In the control and SA groups, samples from the femoral vein, the root of aortic artery, and the coronary sinus did not show differences at the serum level of MPO and hs-CRP. In the UA group, the in-gate percentage of MPO correlated positively with the concentration of hs-CRP (r = 0.78, P < 0.01), and with the level of LDL as well (r = 0.52, P < 0.05); In the AMI group, the average fluorescent intensity of MPO correlated negatively with the concentration of hs-CRP (r = -0.80, P < 0.01), and showed no correlation with the level of LDL (r = 0.22, P > 0.05). CONCLUSIONS: MPO is a better marker for inflammation of the local plaques. It may be one of the mechanisms that MPO induces the transforming from LDL to ox-LDL in plaques vulnerability.

[A correlation study of serum inflammatory factors and intravascular ultrasound features of atherosclerotic plaques in patients with angina pectoris].

OBJECTIVE: To elucidate the relationship between serum inflammatory factors and intravascular ultrasound (IVUS) findings of atherosclerotic plaques in patients with stable and unstable angina. METHODS: Thirteen patients with stable angina (SA) in group A and nineteen patients with unstable angina (UA) in group B underwent study. Concentrations of hsCRP, sVCAM-1 and sICAM-1 were measured by means of Enzyme-Linked-Immunosorbent Assay (ELISA) and IVUS was used to analysis the coronary lesions. Their results were analyzed by correlate analysis. RESULTS: Concentration of hsCRP, sVCAM-1 and sICAM-1 were significantly higher in group B (4.7 mg/L +/- 2.6 mg/L, 789 micro g/L +/- 65 micro g/L and 365 micro g/L +/- 63 micro g/L) than in group A (2.4 mg/L +/- 1.8 mg/L, 544 micro g/L +/- 70 micro g/L and 264 micro g/L +/- 53 micro g/L, P < 0.01, respectively). IVUS found that 69.2% (18/26) patients in group B had soft lipid plaques, while patients in group A mainly had fibrous and mixed plaques, only 13.3% (2/15) had soft plaques. There were more eccentric plaques and EEMA in group B than in group A (P < 0.05, respectively), and PA and lumen area stenosis ratio (LAS) in group B were larger than those of group A (P < 0.01, respectively). Positive remodeling pattern was observed in 65.4% (17/26) lesions in group B while 66.6% (10/15) lesions in group A showed negative remodeling. sICAM-1 correlated well with RI (r = 0.475, P < 0.05) and C-RP with EEMA (r = 0.448, P < 0.05). CONCLUSION: High levels of hsCRP, sVCAM-1 and sICAM-1 are sensitive predictors of unstable angina. The features of unstable atherosclerotic plaques are eccentric, soft plaques, with large plaque areas. The vessel at the lesion shows positive remodeling. Inflammatory reaction correlated well with vascular enlargement and remodeling.