Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Abstract Subject The aim of this study was to compare the predictive values of modified shock index (MSI) and shock index (SI) for 7-day outcome in patients with ST-segment elevation myocardial ...infarction (STEMI). Methods This retrospective study included 160 consecutive patients with STEMI and emergency percutaneous coronary intervention. The blood pressure (BP) and heart rate (HR) measured at emergency department were used to calculate SI (HR/systolic BP) and MSI (HR/mean artery pressure). The major adverse cardiac events (MACE) included all-cause mortality, life-threatening arrhythmias, cardiogenic shock, and Killip class within 7 days. Results Forty-nine patients had increased MSI (≥ 1.4), whereas 72 had increased SI (≥ 0.7). Except the parameters on BP and HR, other parameters were similar between the normal and increased SI groups. However, the increased MSI group had significantly higher age (69.0 ± 13.0 years vs 63.9 ± 12.9 years, P = .025) than the normal MSI group. The 7-day all-cause mortality was 8.8%, and MACE rate was 24.4% in this study. Both increased SI and increased MSI predicted higher MACE rates. However, the odds ratios of increased MSI for all-cause mortality (6.8 vs 3.4), cardiogenic shock (3.0 vs 1.6), life-threatening arrhythmias (9.1 vs 4.6), and MACE (6.8 vs 3.4) were higher than those of increased SI. Modified shock index and SI were independent factor for MACE, but the odds ratio of MSI was higher than of SI (3.05 vs 1.07). Conclusions Both SI and MSI in emergency department could predict the all-cause mortality and MACE rates within 7 days in patients with STEMI, but MSI may be more accurate than SI.
Abstract Background Long-term outcome of drug-eluting stents (DES) for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unclear. This ...study sought to compare the long-term outcomes of biodegradable polymer-coated DES in patients with STEMI versus NSTE-ACS. Methods We explored a post hoc analysis of the 5-year outcome of the CREATE trial in the subgroup of patients with STEMI ( n = 318) versus NSTE-ACS ( n = 1223) who were implanted with biodegradable polymer-coated DES. The primary outcome was the rate of major adverse cardiac events (MACE) at 5 years. Clopidogrel and aspirin for 6 months followed by chronic aspirin therapy were recommended. Results STEMI patients showed a trend of increase in MACE (8.7% vs. 6.8%, log rank p = 0.289) compared to NSTE-ACS patients at 5 years, and a greater risk of cardiac death (5.4% vs. 2.1%, log rank p = 0.003), mainly driven by the higher cardiac death rate within the first month after stent placement (log rank p = 0.003) and the last year of follow-up (log rank p = 0.001). No significant difference in stent thrombosis was found between them (3.1% vs. 2.5%, log rank p = 0.653). Prolonged clopidogrel therapy (>6 months) showed no effect on risk of MACE or stent thrombosis between the two groups (both p for interaction >0.1). Conclusions STEMI patients have a higher risk of cardiac mortality compared with NSTE-ACS patients after biodegradable polymer-coated DES placement, primarily attribute to more cardiac deaths that happened within the first month after the event and the last year of follow-up.
Device availability of mechanical circulatory or respiratory support to the right heart has been limited. The purpose of this study was to investigate the effect of right heart unloading and ...respiratory support with a wearable integrated artificial pump-lung (APL).
The APL device was placed surgically between the right atrium and pulmonary artery in 7 sheep. Anti-coagulation was performed with heparin infusion. The device's ability to unload the right ventricle (RV) was investigated by echocardiograms and right heart catheterization at different bypass flow rates. Hemodynamics and echocardiographic data were evaluated. APL flow and gas transfer rates were also measured at different device speeds.
Hemodynamics remained stable during APL support. There was no significant change in systemic blood pressure and cardiac index. Central venous pressure, RV pressure, RV end-diastolic dimension and RV ejection fraction were significantly decreased when APL device flow rate approached 2 liters/min. Linear regression showed significant correlative trends between the hemodynamic and cardiac indices and device speed. The oxygen transfer rate increased with device speed. The oxygen saturation from the APL outlet was fully saturated (>95%) during support. The impact of APL support on blood elements (plasma free hemoglobin and platelet activation) was minimal.
APL device support significantly unloaded the RV with increasing device speed. The device also provided stable hemodynamics and respiratory support in terms of blood flow and oxygen transfer. The right heart unloading performance of this wearable device needs to be evaluated further in an animal model of right heart failure with long-term support.
Abstract
Purpose:
To explore the offset distribution of pupillary centres, the offset between the pupil centre and the coaxially sighted corneal light reflex (
P-Dist
) and their correlation in ...femtosecond laser combined with excimer laser in situ keratomileusis.
Methods:
Randomly selected 194 patients (398 eyes) who underwent femtosecond-assisted laser in situ keratomileusis with preoperative use of WaveLight Allegro Topolyzer Corneal Topography (WaveLight Laser Technologies AG, Erlangen, Germany) to measure the pupil size and centre position. The
P-Dist
of the patients was recorded by the
X
and
Y
axis eyeball tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system.
Results:
The
P-Dist
was 0.214 ± 0.092 mm in the right eyes and 0.228 ± 0.105 mm in the left eyes (
P
= .041). Under scotopic conditions, the pupil centre of left eye
X
-axis was −0.046 ± 0.091 mm, the right eye was −0.152 ± 0.084 mm, with significant differences (
P
= .015), and the
Y
-axis direction showed no significant changes (
P
= .062). The white to white was positively correlated with changes of pupil diameter (scotopic pupil diameter-photopic pupil diameter) (
r
= 0.270,
P
< .001). The equivalent spherical mirror and measured centroid shift were negatively correlated (
r
= −0.214,
P
= .002).
Conclusion:
The angle kappa of the right eye is smaller than that of the left eye and from scotopic to photopic condition, the pupil centroid shift of both eyes to the nasal inferior side. If the cornea is too large, the low illumination environment should be maintained during the operation to improve the efficiency of pupil matching.
Obstructive sleep apnea (OSA) is an independent risk factor of multisystem injury including liver and cardiovascular system. Chronic intermittent hypoxia (CIH) associated with recurrent apneas in ...patients with OSA is one of the most important causes of the increased various systems injury and oxidative stress induced by CIH is an important pathogenic mechanism. Reports indicated that females are less susceptible to oxidative stress injury. The goal of this study was to explore if there exists gender deference of thioredoxin system (Trx/Txnip) alterations by CIH and to clarify a clue for studying gender disparity of OSA-related multisystem injury. C57BL/6J mice of each gender were exposed to CIH with a fractional inspired O2 (FiO2) nadir of 5%. The oxidative and antioxidant biomarkers were evaluated, including serum OxLDL level and Trx/Txnip expression of liver tissue. Male mice exposed to CIH exhibited significant increases in serum OxLDL level than that of the male control (73.24 ± 22.43 μg/dL, 45.20 ± 28.53 μg/dL, P = 0.032) but no significant difference in the females. Male mice exposed to CIH also exhibited decreased expression of Trx than the female (0.4460 ± 0.1023 versus 1.0454 ± 0.1777, P = 0.013) and increased expression of Txnip than the female (0.0123 ± 0.0476 versus 0.0065 ± 0.0058, P = 0.022). These data suggest that CIH induces thioredoxin system change in a gender-specific fashion in mice.
Abstract Background Endoplasmic reticulum (ER) stress plays an important role in mediating ischemic heart cell death. The aim of this study was to investigate whether manipulation of a key factor of ...the ER stress pathway, eukaryotic translation initiation factor 2 subunit α (eIF2α), can change the natural history of heart failure (HF). Methods HF was induced using coronary artery ligation in adult rats and a selective eIF2α dephosphorylation inhibitor, salubrinal (Sal), was used. Thirty minutes after ligation, rats were randomly assigned to 3 groups: myocardial infarction (MI) plus placebo injections (dimethyl sulfoxide; n = 12), MI plus Sal injection (Sal; n = 12), and MI (HF; n = 12). Hemodynamic parameters were examined. Hearts were harvested for apoptosis assessment after 8 weeks of Sal treatment by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labelling and flow cytometric analysis. Hearts were harvested to determine ER chaperones by Western analysis, real-time polymerase chain reaction and immunohistochemical analysis. Results Cardiac function was significantly improved in Sal-treated rats. Apoptosis was reduced by Sal treatment. Glucose-regulated protein-78 and -94 were increased in HF but normalized by Sal treatment. HF caused a significant increase in eIF2α phosphorylation, which was further increased by Sal treatment, and caspase-12 and phospho-c-JUN NH2 -terminal kinase were markedly increased in rats with HF alone but significantly reduced by Sal treatment. Conclusions Our results suggest that reduction of ER stress and myocardial apoptosis through inhibition of eIF2α dephosphorylation might alter the natural history of HF, which might provide a new approach for its treatment.
Background The methods for increasing the rate of complete small-bowel examinations by capsule endoscopy (CE) demonstrate conflicting results, and it is unknown whether improving the completion rate ...of CE transit is correlated with improvement in diagnostic yield. Objective The aim of this study was to determine whether a higher rate of complete small-bowel examinations results in a higher diagnostic yield of CE. Design Case-control comparison. Setting Tertiary care university hospital. Patients A total of 273 patients underwent conventional CE (group A), and 261 patients underwent real-time CE (group B). Furthermore, the patients in groups A and B were divided into 2 subgroups by pyloric transit time (A1, A2 and B1, B2, respectively). Interventions After swallowing the capsule, each patient was monitored with a real-time viewer in group B, and the patients underwent endoscopic placement if the capsule was delayed in the esophagus or stomach. Main Outcome Measurements Pyloric transit time, small-bowel transit time, the rate of complete small-bowel examinations, and the diagnostic yield. Results The rate of complete small-bowel examinations was significantly higher in group B than in group A (87.4% vs 78.0%, respectively; P = .004). The diagnostic yield was significantly higher in group B2 than in group A2 (60.0% vs 41.7%, respectively; P = .019). Limitations Nonrandomized study. Conclusions Endoscopic placement improves the rate of complete small-bowel examinations, resulting in a higher diagnostic yield of CE.
To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation ...of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC).
In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed.
Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively.
According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.
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