15例儿童心动过速性心肌病的诊疗体会

目的:探讨儿童完全性心动过速性心肌病(pTIC)的临床特点、治疗及预后。方法:回顾分析2009年1月至2016年10月安徽省儿童医院心内科收治的15例完全性心动过速性心肌病患儿的临床表现、心功能、心电图、心脏彩超的特点,观察心律失常控制后的心室率、心脏左室内径大小及心功能恢复情况。结果:15例pTIC患儿以室上性快速心律失常多见(14例),10例单纯药物治疗,3例接受射频消融转为窦性心律,2例失访。随访半年至3年与治疗前比较心室率明显下降[(116±27)次/分vs.(189±28)次/分]、NT-proBNP降低[(404±355)pg/mL vs.(6280±3155)pg/mL]、心脏左室舒张末内径变小[(3.12±0.48)cm vs.(3.69±0.70)cm]、左室射血分数升高[(57.9±9.3)%vs.(42.2±9.5)%]、改良ROSS评分下降[1(0-5)分vs.7(4-10)分]。结论:儿童pTIC由各种快速心律失常引起,心脏扩大和心功能障碍可完全恢复,早期识别、有效治疗的儿童pTIC长期预后良好。     

The Effects of Dietary Chromium(III) Picolinate on Growth Performance, Vital Signs, and Blood Measurements of Pigs During Immune Stress

This experiment used 24 pigs (26.0 kg) to investigate the effects of dietary chromium (Cr) on pigs challenged with lipopolysaccharide (LPS). Following 35 days of diet exposure, the immune stress treatments were: (1) phosphate-buffered saline (PBS) injection and no Cr, (2) LPS injection and no Cr, (3) LPS injection and Cr 1,000 ppb, and (4) LPS injection and Cr 2,000 ppb. At 0 h, PBS or LPS was injected intraperitoneally in each pig. During the first 12 h post-injection, pigs challenged with LPS lost 951 g, while the PBS group gained 170 g (p?<?0.001). Compared with the PBS group, LPS-challenged pigs consumed less feed (p?<?0.01) during the first 24 h. The LPS group had higher rectal temperature at 2 and 4 h and higher respiratory rate at 1.3 and 8.5 h than the PBS group (p?<?0.05). Plasma collected at 3 h had higher cortisol (p?<?0.001) and lower glucose (p?<?0.05) concentrations in the LPS group than the PBS group. However, supplemental Cr did not affect the response variables. Overall, the LPS challenge affects growth performance, vital signs, and plasma variables, but dietary Cr is unable to moderate stress-related effects associated with an LPS challenge.     

Co-culture of dedifferentiated and primary human chondrocytes obtained from cadaveric donor enhance the histological quality of repair tissue: an in-vivo animal study

To compare the quality of the repair tissue in three-dimensional co-culture of human chondrocytes implanted in an in vivo model. Six cadaveric and five live human donors were included. Osteochondral biopsies from the donor knees were harvested for chondrocyte isolation. Fifty percent of cadaveric chondrocytes were expanded until passage-2 (P2) while the remaining cells were cryopreserved in passage-0 (P0). Fresh primary chondrocytes (P0f) obtained from live human donors were co-cultured. Three-dimensional constructs were prepared with a monolayer of passage-2 chondrocytes, collagen membrane (Geistlich Bio-Gide^®), and pellet of non-co-cultured (P2) or co-cultured chondrocytes (P2 + P0c, P2 + P0f). Constructs were implanted in the subcutaneous tissue of athymic mice and left for 3 months growth. Safranin-O and Alcian blue staining were used to glycosaminoglycan content assessment. Aggrecan and type-II collagen were evaluated by immunohistochemistry. New-formed tissue quality was evaluated with an adaptation of the modified O’Driscoll score. Histological quality of non-co-cultured group was 4.37 (SD ±4.71), while co-cultured groups had a mean score of 8.71 (SD ±3.98) for the fresh primary chondrocytes and 9.57 (SD ±1.27) in the cryopreserved chondrocytes. In immunohistochemistry, Co-culture groups were strongly stained for type-II and aggrecan not seen in the non-co-cultured group. It is possible to isolate viable chondrocytes from cadaveric human donors in samples processed in the first 48-h of dead. There is non-significant difference between the numbers of chondrocytes isolated from live or cadaveric donors. Cryopreservation of cadaveric primary chondrocytes does not alter the capability to form cartilage like tissue. Co-culture of primary and passaged chondrocytes enhances the histological quality of new-formed tissue compared to non-co-cultured cells.     

Trimetazidine improves left ventricular function in diabetic patients with coronary artery disease: a double-blind placebo-controlled study

Background

Patients with diabetic cardiomyopathy have an impaired myocardial glucose handling and distal distribution of coronary atherosclerosis. Trimetazidine, an anti-ischemic metabolic agent, improves myocardial glucose utilization though inhibition of fatty acid oxidation. Aim of the present study was to evaluate whether the metabolic effect of trimetazidine on left ventricular function in patients with diabetic cardiomyopathy.

Methods

32 patients (24 males and 8 females, mean (SE) age = 67 ± 6 years) with type 2 diabetes and ischemic cardiomyopathy were randomized to receive either trimetazidine (20 mg, t.d.s.) or placebo (t.d.s.) for six months in a randomized parallel study. Patients performed an echocardiogram at baseline and after 6 months.

Results

Demographic data were comparable between the two groups. After six month baseline left ventricular end-diastolic diameters increased from 62.4 ± 1.7 to 63 ± 2.1 mm in the placebo group, while decreased from 63.2 ± 2.1 to 58 ± 1.6 mm (p < 0.01 compared to baseline) in the trimetazidine group. Compared to baseline, left ventricular ejection fraction increased by 5.4 ± 0.5% (p < 0.05) in the trimetazidine group while remained unchanged in the placebo group -2.4 ± 1.1% (NS), p < 0.01 between groups. A significant improvement in wall motion score index and in the E/A wave ratio was detected in patients treated with trimetazidine, but not in those receiving placebo.

Conclusion

in diabetic patients with ischemic heart disease trimetazidine added to standard medical therapy has beneficial effect on left ventricular volumes and on left ventricular ejection fraction compared to placebo. This effect may be related to the effect of trimetazidine upon cardiac glucose utilization.     

Virtual reality 3D echocardiography in the assessment of tricuspid valve function after surgical closure of ventricular septal defect

Background

Chronic right ventricular apical pacing may have detrimental effect on left ventricular function and may promote to heart failure in adult patients with left ventricular dysfunction.

Methods

A group of 99 pediatric patients with previously implanted pacemaker was studied retrospectively. Forty-three patients (21 males) had isolated congenital complete or advanced atrioventricular block. The remaining 56 patients (34 males) had pacing indication in the presence of structural heart disease. Thirty-two of them (21 males) had isolated structural heart disease and the remaining 24 (13 males) had complex congenital heart disease. Patients were followed up for an average of 53 ± 41.4 months with 12-lead electrocardiogram and transthoracic echocardiography. Left ventricular shortening fraction was used as a marker of ventricular function. QRS duration was assessed using leads V₅ or II on standard 12-lead electrocardiogram.

Results

Left ventricular shortening fraction did not change significantly after pacemaker implantation compared to preimplant values overall and in subgroups. In patients with complex congenital heart malformations shortening fraction decreased significantly during the follow up period. (0.45 ± 0.07 vs 0.35 ± 0.06, p = 0.015). The correlation between the change in left ventricular shortening fraction and the mean increase of paced QRS duration was not significant. Six patients developed dilated cardiomyopathy, which was diagnosed 2 months to 9 years after pacemaker implantation.

Conclusion

Chronic right ventricular pacing in pediatric patients with or without structural heart disease does not necessarily result in decline of left ventricular function. In patients with complex congenital heart malformations left ventricular shortening fraction shows significant decrease.     

Troponin as ischemic biomarker is related with all three echocardiographic risk factors for sudden death in hypertrophic cardiomyopathy (ESC Guidelines 2014)

Background

Sudden cardiac death (SCD) risk stratification is the most important preventive action in patients with hypertrophic cardiomyopathy (HCM). The identification of the ischemia biomarker high sensitive troponin I (hs-TnI) role for this arrhythmic disease may provide additional information for SCD risk stratification. The aim of the study was to compare echocardiographic parameters (prognostic for risk stratification of SCD in HCM) among two subgroups of HCM patients: with elevated hs-TnI versus non-elevated hs-TnI level.

Methods

In 51 HCM patients (mean age 39 ± 8 years, 31 males and 20 females) an echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, was performed. The hs-TnI was measured 24 h later.

Results

By comparing two subgroups of patients, 26 members with hs-TnI positive versus 25 with hs-TnI negative, the study showed that the values of all three parameters were greater: provocable left ventricular outflow tract gradient (LVOTG) – 49.1 ± 45.9 vs 25.5 ± 24.8 mmHg, p = 0.019; left atrial diameter – 50.1 ± 9.6 vs 43.9 ± 9.8 mmHg, p = 0.041; maximal LV thickness – 22.1 ± 5.3 vs 19.9 ± 34 mm, p = 0.029.

Conclusion

The increased value of all three echocardiographic parameters used as risk factors for SCD (ESC Guidelines) is related to the elevated level of hs-TnI in HCM. Due to the high LVOTG – great hs-TnI relationship, exercise stress, both diagnostic and even rehabilitation/training, should be monitored by biomarker control.

     

Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

Background

Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation.

Methods and Results

Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×10⁶ icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs.

Conclusions

Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair.     

Scl gene construction, expression and effect on hemangioma

Hemangioma is a tumor that causes vascular endothelial cell hyperplasia, which commonly occur in newborns. Angiogenesis inhibitor targets the processes of angiogenesis, including the proliferation of vascular endothelial cells. A DNA sequence named Scl was designed, recombined into Pichia Pastoris, expressed by fermenting the engineered strain in a bioreactor, and purified the recombinant Scl by SP-sepharose fast flow. Scl can inhibit CAM angiogenesis. Only 1 μg of Scl significantly suppressed the growth of CAM blood vessel, similar to that of 25 μg of angiostatin. Scl showed a strong cytotoxicity on hemangioma cell (ATCC CRL No. 2587). After the drug acted for 24 h, the OD 570 measured value of the PBS control group averaged 1.873, whereas that of the Sc1 drug group was 0.692 (P < 0.01). Using the DeadEndTM Fluorometric TUNEL System, the detection results showed that 92 % of hemangioma cell apoptosis was observed in the Scl protein group, but only 1.3 % in the PBS control group (P < 0.01). After 2 weeks of treatment with the hemangioma model (cock’s wattle) of the PBS group, 151 blood vessels with 100 views (40×) were obtained, whereas 250 in the PBS group (P < 0.01). During the two-week medication, the hemangioma model of the PBS group increased by 1.18 cm, whereas only 0.58 cm in the Scl drug group (P < 0.01).     

Prognostic Value of Contrast-enhanced Cardiac Magnetic Resonance Imaging in Patients with Newly Diagnosed Non-Ischemic Cardiomyopathy: Cohort Study

Background

Owing to its variable course from asymptomatic cases to sudden death risk stratification is of paramount importance in newly diagnosed non-ischemic cardiomyopathy. We tested whether late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance (CMR) imaging is a prognostic marker in consecutive patients with newly diagnosed non-ischemic cardiomyopathy.

Methods

We enrolled 185 patients who presented for evaluation of newly diagnosed non-ischemic cardiomyopathy. Coronary artery disease was excluded by coronary angiography. Following risk markers were additionally assessed: NYHA functional class (≥II), brain natriuretic peptide (>100 ng/l), troponin I (TnI, ≥0.03 µg/l), left ventricular ejection fraction (LVEF, ≤40%), left ventricular enddiastolic diameter (>55 mm) and QRS duration (>98 ms). Endpoint of the study was the composite of all-cause mortality, heart transplantation, aborted sudden death, sustained ventricular tachycardia or hospitalization due to decompensated heart failure within three years of follow-up.

Results

During median follow-up of 21 months, 54 patients (29.2%) reached the composite endpoint. Ninety-four of the 185 patients (50.8%) were judged LGE-positive. Prognosis of LGE-positive patients was significantly worse than that of LGE-negative patients (cumulative 3-year event rates of 67.4% in LGE-positive and 27.2% in LGE-negative patients, respectively; p = 0.021). However, in multivariable analysis, presence of LGE was not an independent predictor of outcome. Only LVEF ≤40% and TnI ≥0.03 µg/l were independent risk predictors of the composite endpoint yielding relative risks of 3.9 (95% CI 1.9–8.1; p<0.0001) and 2.2 (95% CI 1.2–4.0; p = 0.014), respectively.

Conclusions

In consecutive patients presenting with newly diagnosed non-ischemic cardiomyopathy, LGE-positive patients had worse prognosis. However, only traditional risk parameters like left ventricular performance and cardiac biomarkers but not presence of LGE were independent risk predictors.     

Asynchronisme cardiaque chez le sujet à QRS fin. Étude par échocardiographie Doppler tissulaire

ObjectiveTo assess the prevalence of different types of cardiac dyssynchrony by pulsed Doppler ultrasound and Doppler tissue in patients with narrow QRS with or without left ventricular systolic dysfunction.MethodologyProspective, cross-sectional survey at the Institute of Cardiology of Abidjan, from January to April 2012, in subjects with narrow QRS. Group 1: patients with dilated cardiomyopathy with severe left ventricular dysfunction (left ventricular end diastolic diameter greater than 60 mm and/or 30 mm/m² and ejection fraction less than 35% NYHA stage IV). Group 2: normal subjects with normal echocardiography. All patients underwent an evaluation including tissue Doppler search for different types of dyssynchrony (atrioventricular, interventricular and left intraventricular).ResultsPatients in group 1 were significantly older (51.5 ± 15.8 vs. 35.8 ± 7.8, P = 0.03), with larger left ventricular diameters and significantly higher pulmonary systolic pressure. The prevalence of different types of dyssynchrony in group 1 were: atrioventricular dyssynchrony 43.7%, interventricular dyssynchrony 37.5%, left ventricular dyssynchrony 65.6%. Group 2: atrioventricular dyssynchrony 0%, interventricular dyssynchrony 0%, left ventricular dyssynchrony 35%.ConclusionA large proportion of patients with left ventricular systolic dysfunction and narrow QRS have cardiac dyssynchrony and left ventricular dyssynchrony can be found in healthy patients. This raises the problem of the specificity of Doppler ultrasound criteria using cardiac tissue Doppler to assess cardiac dyssynchrony.     

Comparison of mitral annulus geometry between patients with ischemic and non-ischemic functional mitral regurgitation: implications for transcatheter mitral valve implantation

Background

Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR). Mitral valve (MV) geometry quantification is of paramount importance for success of the procedure and transthoracic 3D echocardiography represents a useful screening tool. Accordingly, we sought to asses MV geometry in patients with functional MR (FMR) that would potentially benefit of TMVR, focusing on the comparison of mitral annulus (MA) geometry between patients with ischemic (IMR) and non ischemic mitral regurgitation (nIMR).

Methods

We retrospectively selected 94 patients with severe FMR: 41 (43,6%) with IMR and 53 (56,4%) with nIMR. 3D MA analysis was performed on dedicated transthoracic 3D data sets using a new, commercially-available software package in two moments of the cardiac cycle (early-diastole and mid-systole). We measured MA dimension and geometry parameters, left atrial and left ventricular volumes.

Results

Maximum (MA area 10.7?±?2.5 cm² vs 11.6?±?2.7 cm², p?>?0.05) and the best fit plane MA area (9.9?±?2.3 cm² vs 10.7?±?2.5 cm², p?>?0.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8?±?2.3 cm² vs 10.8?±?2.7 cm², p?<?0.05) and perimeter (11.2?±?1.3 cm vs 11.8?±?1.5 cm, p?<?0.05) with longer and larger leaflets, and wider aorto-mitral angle (135?±?10° vs 141?±?11°, p?<?0.05). Conversely, the area of MA at the best fit plane did not differ between IMR and nIMR patients (9?±?1.1 cm² vs 9.9?±?1.5 cm², p?>?0.05).

Conclusions

Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be taken into account to tailor prosthesis’s selection.

Trial registration

N.A.

     

Cardioprotective Efficacy of a Novel Antioxidant Mix VitaePro Against Ex Vivo Myocardial Ischemia–Reperfusion Injury

Circumstantial evidence frequently implicates oxygen-derived free radicals and oxidative stress as mediators of myocardial ischemia/reperfusion (I/R) injury. Therefore, external supplementation of natural antioxidants plays a main role as cardioprotective compounds. This study was designed to evaluate the cardioprotective effect of VitaePro (70 mg/kg body weight, 21 days), a novel antioxidant mix of astaxanthin, lutein and zeaxanthin in a rat ex vivo model of ischemia/reperfusion injury. The cardioprotective effect of VitaePro was also compared with vitamin E (70 mg/kg body weight, 21 days) treatment. Rats were randomized into control I/R (CIR), VitaePro I/R (VPIR) and Vitamin E I/R (VEIR). After 21 days of oral treatment, isolated hearts from each group were subjected to 30 min of ischemia followed by 2 h of reperfusion. In the VPIR group compared to CIR and VEIR groups at 2 h of reperfusion, increased left ventricular functional recovery, such as left ventricular developed pressure (92.7 ± 0.7 vs. 85.3 ± 0.3 and 89.4 ± 1.2 mm Hg), dp/dt _max (2518.7 ± 77.9 vs. 1962.5 ± 24 and 2255.7 ± 126.6 mm Hg/s), and aortic flow (21.5 ± 1.36 vs. 4.4 ± 0.6 and 13.2 ± 1.02 ml/min) were observed. The infarct size (27.68 ± 1.7 vs. 45.4 ± 1.8 and 35.4 ± 0.6%), apoptotic cardiomyocytes (61.7 ± 10.6 vs. 194.1 ± 14.8 and 118.7 ± 15.4 counts/100 HPF) and thiobarbituric acid reactive substances levels (80 ± 3 vs. 127 ± 5 and 103 ± 2 nM/mg tissue) also were decreased in VPIR group when compared to CIR and VEIR. As evidenced by the data, administration of vitamin E offered substantial cardioprotection to I/R injury, but VitaePro enhanced cardioprotection significantly more than vitamin E treatment. Taken in concert, the results of this study suggests that the oral ingestion of VitaePro protects myocardium from ischemia/reperfusion injury by decreasing oxidative stress and apoptosis, which may be of therapeutic benefit in the treatment of cardiovascular complications. However, further in vivo animal and human intervention studies are warranted before establishing any recommendations about usage of VitaePro for human cardiovascular complications.     

Latent pulmonary hypertension in atrial septal defect: Dynamic stress echocardiography reveals unapparent pulmonary hypertension and confirms rapid normalisation after ASD closure

Objective

Closure of atrial septal defects (ASD) prevents pulmonary hypertension, right heart failure and thromboembolic stroke. The exact timing for ASD closure is controversial.

Methods

In a prospective study to address the question whether unapparent pulmonary hypertension can be revealed prior to right ventricular (RV) remodelling, patients were investigated before and 6, 12, and 24 months after ASD closure using exercise stress echocardiography (ESE) and ergospirometry (n?=?24).

Results

At rest, RV systolic pressure (RVSP) was normal in 58.8 %, slightly elevated in 26.5 %, and moderately elevated in 11.8 %. One patient showed severe pulmonary hypertension. During ESE, all patients with normal RVSP at rest exhibited an increase (25.7?±?1.2 mmHg vs. 45.3?±?2.3 mmHg, p?<?0.001). After closure the RVSP was lower, both at rest and ESE. RV diameters decreased too. Tricuspid annulus plane systolic excursion (TAPSE) at rest remained lower after closure (24.0?±?0.9 vs. 22.0?±?0.9 mm, p?<?0.05). TAPSE in ESE was elevated, and stayed stable after closure (30.1?±?1.8 mm vs. 29.3?±?1.6 mm). Before closure, RV systolic tissue velocities (s^a) at rest were normal and decreased after closure (14.0?±?1.0 cm/s vs. 11.5?±?0.7 (6 month) vs. 10.6?±?0.5 cm/s (12 month), p?<?0.05). During ESE, s^a velocity was similar before and after closure (23.0?±?1.3 cm/s vs. 23.3?±?1.9 cm/s). Maximal oxygen uptake (VO₂/kg) did not differ between baseline and follow-ups.

Conclusion

Latent pulmonary hypertension may become apparent in ESE. ASD closure leads to a significant reduction in this stress-induced pulmonary hypertension and to a decrease in the right heart diameters indicating reverse RV remodelling. RV functional parameters at rest did not improve. The VO₂/kg did not change after ASD closure.     

Towards a characterization of the locomotor activity rhythm of the desertic species Porcellio olivieri (Crustacea,Isopoda) from Gabes (South of Tunisia)

The locomotor activity rhythm of the isopod, Porcellio olivieri, was investigated in Gannouch site in the south of Tunisia. The rhythm was monitored under constant temperature in individual animals in winter under two simultaneous regimens: the light–dark (LD) cycle and the continuous darkness (DD). Results revealed that whatever regimens, actograms, and mean activity curves showed that specimens of P. olivieri concentrated their activity during the experimental and subjective night. The species exhibited a locomotor rhythm period significantly shorter under LD (T = 23h13 ± 0h44) than DD (τ = 24h28 ± 0h58). However, the locomotor activity rhythm was less stable and the individuals were significantly more active under entraining conditions than constant darkness. The activity pattern of this species will be discussed as an adaptative strategy to respond to environmental conditions.     

Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy

Background aimsMesenchymal stromal cells (MSC) may improve cardiac function following myocardial infarction. MSC can differentiate into cardiomyocytes and endothelial cells while exerting additional paracrine effects. There is limited information regarding the efficacy of route for MSC treatment of severe dilated cardiomyopathy (DCM). The aim of this study was to demonstrate the clinical safety, feasibility and efficacy of direct intramyocardial and intracoronary administration of autologous bone marrow-derived MSC treatment for no-option patients with chronic severe refractory DCM.MethodsTen symptomatic patients with DCM and refractory cardiac function, despite maximum medical therapy, were selected. Five had ischemic DCM deemed unlikely to benefit from revascularization alone and underwent bypass operations with concurrent intramyocardial MSC injection (group A). Two patients had previous revascularization and three had non-ischemic DCM and received intracoronary MSC injection (group B).ResultsGroup A and B patients received 0.5–1.0 × 10⁶ and 2.0–3.0 × 10⁶ MSC/kg body weight, respectively. All patients remained alive at 1 year. There were significant improvements from baseline to 6 and 12 months in left ventricular ejection fraction and other left ventricular parameters. Scar reduction was noted in six patients by 12 months.ConclusionsAutologous bone marrow MSC treatment is safe and feasible for treating chronic severe refractory DCM effectively, via intracoronary or direct intramyocardial administration at prescribed doses.     

The changes of technetium-99m-labeled annexin-V in delayed anesthetic preconditioning during myocardial ischemia/reperfusion

This study was designed to use real-time imaging to test the hypothesis that delayed cardiac protection induced by volatile anesthetics inhibits apoptosis. Rats were divided into two groups. One group was exposed to 120 min of 33 % O₂ [control group (CON group)] and the other group was exposed to 2.5 % sevoflurane in 33 % O₂ for 120 min [sevoflurane group (SEVO group)]. Both groups were allowed to return to their cages for 24 h. After 24 h recovery, all rats underwent 30 min myocardial ischemia by occluding coronary artery followed by 2 h of reperfusion. After reperfusion, technetium-99m-labeled annexin-V was administered intravenously to identify apoptosis. Left ventricular samples were obtained to measure infarct size and radionuclide imaging and caspase-3. Radionuclide imaging indicated that apoptosis was reduced in SEVO group (0.78 % ± 0.82) when compared with the CON group (1.15 % ± 0.61), and the infarct size was also decreased in the SEVO group (40 % ± 7). The transferase dUTP nick end labeling (TUNEL)-positive cardiomyocytes in the SEVO group (16 % ± 6) were significantly decreased in the peri-infarct zone when compared with the CON group (28 % ± 4). After reperfusion, caspase-3 expression was significantly blunted in the SEVO group than in CON group (50 % ± 11 vs. 68 % ± 10, p < 0.05). This study used technetium-99m-labeled annexin-V of real-time imaging to detect cardiomyocyte apoptosis and the results were confirmed by the TUNEL assay and caspase-3 expression. We concluded that delayed volatile anesthetic preconditioning (APC) protects against I/R in vivo. The method of technetium-99m-labeled annexin-V of real-time imaging can be used to detect cardiomyocyte apoptosis in delayed APC during ischemia/reperfusion.     

Calpain I Activity and Its Relationship with Hippocampal Neuronal Death in Pilocarpine-Induced Status Epilepticus Rat Model

This study aims to establish pilocarpine-induced rat model of status epilepticus (SE), observe the activity of calpain I in the rat hippocampus and the subsequent neuronal death, and explore the relationship between calpain I activity and neuronal death in the hippocampus. Fifty-eight adult male Wistar rats were assigned randomly into either control group (n = 8) or epilepsy group (n = 50). SE was induced in the epilepsy group using pilocarpine. Before the injection, the rats were given atropine sulfate to reduce the side effect of pilocarpine. All rats in the seizure group were grouped into either SE or non-SE, depending on whether they developed convulsive seizures. The rats in SE group were treated with chloral hydrate to stop seizures after 60 min. Control animals were treated with the same dose of 0.9 % saline. All rats were monitored for seizures. At 24 h after SE, the rats’ left brain tissues were stained by HE and TUNEL. Neuronal necrosis and apoptosis in the hippocampal CA3 area were observed. Calpain I activity in the right hippocampus was also observed using western blotting. Eighty percent of the rats in the seizure group developed SE, of which 35 % died. No rat died in both the control and non-SE groups. At 24 h after SE, the number of HE-stained neurons decreased (SE group: 55.19 ± 8.23; control group: 102.13 ± 3.73; non-SE group: 101.2 ± 2.86) and the number of TUNEL-positive neurons increased (SE group: 4.91 ± 1.35; non-SE and control group: 0). No obvious changes were observed in the neurons of the control and non-SE group animals. The 76 kDa cleavage of calpain I (the average optical density ratio is 0.096 ± 0.015) emerged in the SE group. Neuronal death has a direct relationship with calpain I activity. There is high success rate and lower death rate for pilocarpine to induce SE. At 24 h after SE, activity of calpain I, neuronal necrosis and apoptosis increased in the hippocampus. Neuronal death has a direct relationship with calpain I activity, which suggests that calpain I plays an important role in neuronal damage during SE.     

Catheter ablation of symptomatic idiopathic ventricular arrhythmias

Aims

This study was designed to gain insight into the patient characteristics, results and possible complications of ablation procedures for symptomatic idiopathic premature ventricular complexes (PVC) and idiopathic ventricular tachycardia (VT).

Methods

Data were collected from all patients who underwent radiofrequency catheter ablation for symptomatic PVCs and idiopathic VT in the Catharina Hospital between 1 January 2011 and 31 December 2015. The procedural endpoint was elimination or non-inducibility of the clinical arrhythmia. Successful sustained ablation was defined as the persistent elimination of at least 80% of the PVCs or the absence of VTs at follow-up. In case of suspected PVC-induced cardiomyopathy, the systolic left ventricular function was reassessed 3 months post procedure.

Results

Our cohort consisted of 131 patients who underwent one or more ablation procedures; 99 because of symptomatic premature ventricular complexes, 32 because of idiopathic VT. In total 147 procedures were performed. The procedural ablation success rate was 89%. Successful sustained ablation rate was 82%. Eighteen (13.2%) patients had suspected PVC-induced cardiomyopathy. In 15 of them (83%), successful sustained ablation was achieved and the left ventricular ejection fraction improved from a mean of 39% (±8.8) to 55.4% (±8.1). Most arrhythmias originated from the right ventricular outflow tract (60%) or aortic cusps (13%). Complications included three tamponades.

Conclusion

Catheter ablation therapy for idiopathic ventricular arrhythmias is very effective with a sustained success rate of 82%. In patients with PVC-induced cardiomyopathy, it leads to improvement of systolic left ventricular function. However, risk for complications is not negligible, even in experienced hands.

     

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative <Emphasis Type="Italic">FBN1</Emphasis> mutations

Background

Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation.

Methods

In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up.

Results

Changes in biventricular dimensions were assessed in 163 Marfan patients (48?% female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. ?8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. ?18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. ?8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. ?7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28).

Conclusion

Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.

     

Sporicidal efficacy of genipin: a potential theoretical alternative for biomaterial and tissue graft sterilization

Terminal sterilization of musculoskeletal allografts by gamma radiation minimizes the risk of disease transmission but impairs allograft mechanical properties. Commonly employed crosslinking agents can sterilize tissues without affecting mechanical properties adversely; however, these agents are toxic. Genipin is reported to be a benign crosslinking agent that strengthens mechanical properties of tissues; however, the antimicrobial capacity of genipin is largely unknown. The present study’s aims were: (1) to assess the sporicidal potential of genipin, (2) to improve antimicrobial capacity by changing chemical and physical treatment conditions. To establish genipin’s sterilization potential Bacillus subtilis var. niger spore strips were treated with 0–10 % genipin in PBS or in 1:1 DMSO:PBS up to 72 h at room temperature (RT). Sterilizing doses and concentrations of genipin were used to treat B. pumilus and Geobacillus stearothermophilus spores to assess broader spectrum sporicidal activity of genipin. Scanning electron microscopy (SEM) was performed to evaluate gross morphological changes after genipin treatment. Optimal sterilization conditions were determined by evaluating the effects of temperature (RT-50 °C), DMSO:PBS ratio (0:100–100:0), and treatment duration (24–72 h) on B. subtilis. Genipin penetration of full thickness bovine patellar tendon and cortical bone specimens was observed to assess the feasibility of the agent for treating grafts. Initial studies showed that after 72 h of treatment at RT with 0.63–10 % genipin/DMSO:PBS B. subtilis spore strips were sterilized; 0.63 % genipin/PBS did not sterilize spore strips at 72 h at RT. Genipin doses and concentrations that sterilized B. subtilis spore strips sterilized B. pumilus and G. stearothermophilus spore strips. SEM revealed no gross morphological differences between untreated and treated spores. Treatment optimization resulted in sterilization within 24 h with 100 % PBS, and DMSO facilitated sporicidal activity. Genipin penetrated full thickness patellar tendon specimens and 3.72 ± 0.58 mm in cortical bone specimens. Genipin sterilizes B. subtilis, B. pumilus, and G. stearothermophilus spore strips. It penetrates soft and hard tissues at doses previously shown to be non-toxic and to improve mechanical strength in collagen-rich soft tissues. Further studies are indicated to assess genipin’s effects on the mechanical properties of genipin-sterilized grafts, the ability of genipin to eradicate infectious species other than spores, and to assess whether sterilant activity persists after penetrating tissues and biomaterials.