Monocrotaline-induced pulmonary hypertension with sufficient tricuspid regurgitation in a rat model

Background and purpose

It is well known that monocrotaline (MCT) induces pulmonary hypertension (PH) in rats. This model is very useful for understanding the physiology of PH and developing treatments for PH. However, it is very difficult to estimate pulmonary artery pressure (PAP) in this model. The purpose of this study is to establish a PH model with sufficient tricuspid regurgitation (TR) to evaluate PAP.

Method

We studied 17 male rats that received 15 injections of 5?mg/kg/day of MCT (PH) or vehicle (control). Three weeks after the first MCT injection, we measured left and right ventricular dimensions, the ratio of acceleration to ejection time in pulmonary flow, and the development of TR using an echocardiograph (SONOS5500) with a s12 probe (frequency: 5–12?MHz, frame rate: 120?Hz).

Results

The right ventricular end-diastolic area in the PH group was significantly larger than that in the control group. The acceleration time/ejection time ratio and velocity time integral of the pulmonary artery in the PH group were smaller than those in the control group. In 78?% of rats in the PH group, sufficient TR was observed and estimated PAP was 75.4?±?13.8?mmHg. There was a good correlation between PAP estimated by a Doppler method and directly measured right ventricular pressure (r?=?0.94, P?<?0.0001).

Conclusion

Fifteen injections of 5?mg/kg/day of MCT could induce PH with sufficient TR in rats. Transthoracic echocardiography could be used for monitoring the progress of PH in the rat model.     

Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility

Objective

Prostacyclins have been suggested to exert positive inotropic effects which would render them particularly suitable for the treatment of right ventricular (RV) dysfunction due to acute pulmonary hypertension (PHT). Data on this subject are controversial, however, and vary with the experimental conditions. We studied the inotropic effects of epoprostenol at clinically recommended doses in an experimental model of acute PHT.

Design and setting

Prospective laboratory investigation in a university hospital laboratory.

Subjects

Six pigs (36?±?7?kg).

Interventions

Pigs were instrumented with biventricular conductance catheters, a pulmonary artery (PA) flow probe, and a high-fidelity pulmonary pressure catheter. Incremental doses of epoprostenol (10, 15, 20, 30, 40?ng?kg^–1?min^–1) were administered in undiseased animals and after induction of acute hypoxia-induced PHT.

Measurements and results

In acute PHT epoprostenol markedly reduced RV afterload (slopes of pressure-flow relationship in the PA from 7.0?±?0.6 to 4.2?±?0.7?mmHg?min?l^–1). This was associated with a paradoxical and dose-dependent decrease in RV contractility (slope of preload-recruitable stroke-work relationship from 3.0?±?0.4 to 1.6?±?0.2?mW?s?ml^–1; slope of endsystolic pressure-volume relationship from 1.5?±?0.3 to 0.7?±?0.3?mmHg?ml^–1). Left ventricular contractility was reduced only at the highest dose. In undiseased animals epoprostenol did not affect vascular tone and produced a mild biventricular decrease in contractility.

Conclusions

Epoprostenol has no positive inotropic effects in vivo. In contrast, epoprostenol-induced pulmonary vasodilation in animals with acute PHT was associated with a paradoxical decrease in RV contractility. This effect is probably caused indirectly by the close coupling of RV contractility to RV afterload. However, data from normal animals suggest that mechanisms unrelated to vasodilation are also involved in the observed negative inotropic response to epoprostenol.     

Right ventricular hypertrophy after atrial switch operation: normal adaptation process or risk factor? A cardiac magnetic resonance study

Background

Systemic right ventricle (RV) hypertrophy and impaired function occur after atrial switch for dextro-transposition of the great arteries (d-TGA). Echocardiography is limited in its ability to assess the RV. We sought to evaluate systemic RV myocardial-mass index (MMI) and function after atrial switch and to analyse the role of hypertrophy for ventricular function with special consideration of the interventricular septal (IVS) movement.

Methods

Thirty-seven consecutive patients (median age 22.9?years) after atrial switch were studied using cardiac magnetic resonance imaging (1.5T Intera, Philips) with a dedicated 5-channel phased-array surface cardiac coil. Cine steady-state free-precession sequences were acquired to obtain myocardial masses and function. The systolic movement of the IVS was defined as positive when moving towards the centroid of the RV and was defined as non-positive otherwise. Patient parameters were compared to controls.

Results

The systemic RVs were significantly larger (p?<?0.001) than the left ventricles of the control group, systolic function was significantly impaired (p?<?0.001) and MMI including the IVS was comparable (p?=?n.s.). RV-MMI excluding the IVS and RV ejection fraction (EF) demonstrated a quadratic correlation (r?=?0.6, p?<?0.001), meaning that patients with RV-MMI ≤29?g/m² and >68?g/m² had a reduced level of systolic function. Positive septal movement improved RV function compared with non-positive septal movement (p?=?0.024).

Conclusions

There seems to be a range of beneficial RV hypertrophy after atrial switch in which a sufficient RV-EF can be expected. A positive septal movement, probably the result of hypertrophic septal RV fibres, improves RV function and might be regarded as a beneficial contraction pattern.     

Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia

Objective

Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia.

Design

Prospective experimental study

Animals

Eighteen anesthetized and ventilated piglets

Interventions

Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16?mg/l). Ceftazidime was administered either through a continuous infusion of 90?mg/kg per 24?h after a bolus of 30?mg/kg or by an intermittent infusion of 30?mg/kg per 8?h.

Measurements and results

Piglets were killed 24?h after the initiation of continuous ceftazidime (n?=?6), and 1?h (peak, n?=?6) and 8?h (trough, n?=?6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7?±?3.8?μg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1?±?2.4?μg/g and 0.6?±?1?μg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.10³ vs. 4.10²?cfu/g).

Conclusions

Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.     

Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial

Purpose

Cardiac side effects of granisetron have been studied mostly in adult patients that are using cardiotoxic chemotherapeutics. There is limited evidence in pediatric age group and no information in pediatric oncology patients with non-cardiotoxic chemotherapeutics.

Methods

In this prospective, crossover randomized study, the cardiac side effects of granisetron are compared in pediatric oncology patients who had carboplatin based chemotherapy. They were randomized to receive either 10 or 40 μg kg^?1 dose^?1 of granisetron before each cycle of chemotherapy. We drew blood for creatine phosphokinase (CPK), CPK-muscle band (MB) and Troponin-T before and 24?h after administering granisetron. Electrocardiography (ECG) tracings were taken at 0, 1, 2, 3, 6 and 24?h of granisetron. Twenty-four hours Holter ECG monitorisation was performed after each granisetron infusion.

Results

A total of 16 patients (median 8.7?years of age) were treated with weekly consecutive courses of carboplatin. There was bradycardia (p?=?0.000) in patients that had granisetron at 40 μg/kg and PR interval was shortened in patients that had granisetron at 10 μg/kg dose (p?=?0.021). At both doses of granisetron, QTc interval and dispersion were found to be similar. CPK, CK-MB and Troponin-T values were found to be normal before and 24?h after granisetron infusion.

Conclusions

As the first study that has studied cardiac side effects of granisetron in patients that are not using cardiotoxic chemotherapeutics, we conclude that granisetron at 40 μg kg^?1 dose^?1 causes bradycardia only. We have also demonstrated that granisetron does not cause any clinically cardiac side effects either at 10 or 40 μg kg^?1 dose^?1. However, our results should be supported by prospective randomized studies with larger samples of patient groups.     

Right ventricular function in grown-up patients after correction of congenital right heart disease

Aims

We investigated whether a correlation exists between biomarkers of the neurohumoral system and clinical markers in grown-up patients with congenital heart disease (GUCH) and right ventricular function.

Methods and results

Prospective, cross-sectional, multicenter study of 104 GUCH patients (median) 16?years (range 6?C43?years) after corrective surgery with RV pressure and/or volume overload and 54 healthy controls. Clinical, functional, and laboratory parameters were assessed. Natriuretic peptide levels were significantly increased in GUCH patients (NTproBNP 101 vs. 25?pg/ml, p?<?0.001), but we observed no differences in norepinephrine, aldosterone, angiotensin II and Endothelin-1 levels. NTproBNP correlated significantly with clinical markers such as NYHA classification, prolonged QRS duration and reduced exercise capacity (VO₂ peak) (all p?<?0.001), as well as self-reported quality of life (p?<?0.001). MRI and echocardiography derived RV volumes were elevated and ejection fraction reduced in the patients (both p?<?0.001). Tissue Doppler parameter showed significantly restricted ventricular longitudinal systolic function (longitudinal tricuspid valve movement, 1.7 vs. 2.3?cm, p?<?0.001), suggesting stiffness and reduced RV compliance.

Conclusion

In conclusion, grown-up patients with congenital right heart disease NTproBNP correlates well with various clinical markers of RV failure, such as prolongation of QRS duration, exercise capacity, echocardiography and MRI parameters, and quality of life.     

Effects of exercise training on exercise capacity in patients with non-small cell lung cancer receiving targeted therapy

Purpose

Peak oxygen consumption (VO_2peak) is an important predictive factor for long-term prognosis in patients with non-small cell lung cancer (NSCLC). The purpose of this study was to investigate whether 8 weeks of exercise training improves exercise capacity, as assessed by VO_2peak, and other related factors in patients with NSCLC receiving targeted therapy.

Methods

A total of 24 participants with adenocarcinoma were randomly assigned to either the control group (n?=?11) or the exercise group (n?=?13). Subjects in the exercise group participated in individualized, high-intensity aerobic interval training of exercise. The outcome measures assessed at baseline and after 8?weeks were as follows: VO_2peak and the percentage of predicted VO_2peak (%predVO_2peak), muscle strength and endurance of the right quadriceps, muscle oxygenation during exercise, insulin resistance as calculated by the homeostasis model, high-sensitivity C-reactive protein, and quality of life (QoL) questionnaire inventory.

Results

No exercise-related adverse events were reported. After exercise training, VO_2peak and %predVO_2peak increased by 1.6?mL?kg^?1?min^?1 and 5.3% (p?<?0.005), respectively; these changes were associated with improvements in circulatory, respiratory, and muscular functions at peak exercise (all p?=?0.001). The exercise group also had less dyspnea (p?=?0.01) and favorably lower fatigue (p?=?0.05) than baseline.

Conclusions

Patients with NSCLC receiving targeted therapy have quite a low exercise capacity, even with a relatively high QoL. Exercise training appears to improve exercise capacity and alleviate some cancer-related symptoms.     

Positron Emission Tomography of 64Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

Purpose

This study aims to evaluate ⁶⁴Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.

Procedures

⁶⁴Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n?=?3) that received 7.4?MBq/dose, (b) with pre-dose (CD20TM, n?=?6) received 2?mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4?MBq/dose, and (c) without pre-dose (CD20TM, n?=?6) PETRIT alone received 7.4?MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72?h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.

Results

PETRIT was obtained with a specific activity of 545?±?38.91?MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24?h, spleenic uptake of PETRIT%ID/g (mean?±?STD) with and without pre-dose was 1.76?±?0.43% and 16.5?±?0.45%, respectively (P value?=?0.01). Liver uptake with and without pre-dose was 0.41?±?0.51% and 0.52?±?0.17% (P value?=?0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8?±?0.4???Sv/MBq and the spleen at 99?±?4???Sv/MBq, respectively.

Conclusions

PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.     

Transpulmonary thermodilution measurements are not affected by continuous veno-venous hemofiltration at high blood pump flow

Purpose

To assess whether continuous veno-venous hemofiltration (CVVH) with high blood pump flow alters the measurements of cardiac index (CI), global end-diastolic volume indexed (GEDVI), and extravascular lung water indexed (EVLWI) performed by transpulmonary thermodilution.

Methods

Sixty-nine patients were included if they were monitored by a PiCCO2 device and received CVVH through a femoral (n?=?62) or an internal jugular (n?=?7) dialysis catheter. The blood pump flow was set at 250?mL/min (n?=?31) or 350?mL/min (n?=?38) and the filtration flow at 6,000?mL/h. A first set of data was collected with a first transpulmonary thermodilution (TD_on). The blood pump was stopped and the continuous CI derived from pulse contour analysis was recorded (PC_off). A second data set (TD_off) was collected before and a last one (TD_on-last) after restarting the blood pump.

Results

$ {\text{CI}}_{{{\text{TD}}_{\text{on}} }} $ , $ {\text{CI}}_{{{\text{PC}}_{\text{off}} }} $ , $ {\text{CI}}_{{{\text{TD}}_{\text{off}} }} $ , and $ {\text{CI}}_{{{\text{TD}}_{{{\text{on}} - {\text{last}}}} }} $ were not significantly different in patients with a femoral dialysis catheter (3.49?±?0.96, 3.51?±?0.96, 3.51?±?0.99, and 3.44?±?1.00?L?min^?1?m^?2, respectively). This was observed with a blood pump flow at 350?mL/min and at 250?mL/min. In these patients with a femoral dialysis catheter, GEDVI did not significantly change when the blood pump was stopped. EVLWI significantly decreased when the blood pump was stopped but to a non-clinically relevant extent (?0.3?±?0.8?mL/kg). No significant changes in CI, GEDVI, and EVLWI were observed in patients with an internal jugular dialysis catheter over the study period.

Conclusions

CVVH with a high blood flow pump does not alter the transpulmonary thermodilution measurements of CI, GEDVI, and EVLWI.     

Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block

Background

The impact of atrial fibrillation (AF) on heart failure (HF) was evaluated in patients with preserved left ventricular (LV) function and long-term right ventricular (RV) pacing for complete heart block.

Methods

Clinical, echocardiographic, and laboratory parameters of HF were assessed in 35 patients with established AF who had undergone ablation of the atrioventricular node and pacemaker implantation (Group A) and 31 patients who received dual-chamber pacing for spontaneous complete heart block (Group B).

Results

During a follow-up period of 12.7?±?7.5?years, New York Heart Association (NYHA) functional class increased from 1.3?±?0.5 to 2.1?±?0.6 (p?p?p?p?=?0,21) in Group B. At the end of follow-up, markers of LV function were moderately depressed in Group A compared with those in Group B: NYHA class 2.1?±?0.6 versus 1.6?±?0.7, p?=?0.001; LVEF 53.0?±?8.2 versus 56.9?±?7.0?%, p?p?p?10?%, increasing NYHA class ≥1, and NT-proBNP levels >1,000?pg/ml.

Conclusions

Permanent AF was associated with adverse effects on LV function and symptoms of HF in patients with long-term RV pacing for complete heart block, and appears to play an important role in the development of HF in this specific patient cohort.     

Pulmonary hypertension is ameliorated in mice deficient in thrombin‐activatable fibrinolysis inhibitor

Summary. Background: The fibrinolytic system has been implicated in the pathogenesis of pulmonary hypertension (PH). Thrombin‐activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and therefore its absence would be expected to increase fibrinolysis and ameliorate PH. Objective: The objective of the present study was to evaluate the effect of TAFI deficiency on pulmonary hypertension in the mouse. Methods and results: PH was induced in C57/Bl6 wild‐type (WT) or TAFI‐deficient (KO) mice by weekly subcutaneous treatment with 600 mg kg^?1 monocrotaline (MCT) for 8 weeks. PH was inferred from right heart hypertrophy measured using the ratio of right ventricle‐to‐left ventricle‐plus‐septum weight [RV/(LV+S)]. Pulmonary vascular remodeling was analyzed by morphometry. TAFI‐deficient MCT‐treated and wild‐type MCT‐treated mice suffered similar weight loss. TAFI‐deficient MCT‐treated mice had reduced levels of total protein and tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), transforming growth factor‐β (TGF‐β) and monocyte chemoattractant protein‐1 (MCP‐1) in bronchial alveolar lavage compared with wild‐type MCT‐treated mice. The ratio of RV to (LV+S) weight was significantly higher in WT/MCT than in KO/MCT mice. The pulmonary artery wall area and vascular stenosis were both greater in MCT‐treated WT mice compared with MCT‐treated TAFI‐deficient mice. Conclusions: TAFI‐deficient MCT‐treated mice had less pulmonary hypertension, vascular remodeling and reduced levels of cytokines compared with MCT‐treated WT animals, possibly as a result of reduced coagulation activation.     

Assessing Lung Inflammation After Nanoparticle Inhalation Using 2-deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography Imaging

Purpose

The aim of the present study was to evaluate the use of 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats.

Procedures

Healthy, male Sprague–Dawley rats (n?=?30) were divided in two groups of 15 animals each. Animals from one group (n?=?15) were submitted to ZnO NPs inhalation in a chamber (10 nm to 4 μm particle size; maximum in number concentration, ～200 nm; concentration?=?245 mg/m³). Animals from the other group (n?=?15, sham group) were also exposed following the same procedure, but no NPs were introduced into the chamber. Six animals per group were submitted to [¹⁸F]FDG-positron emission tomography (PET) studies at days 1, 7, and 28 after exposition, and the [¹⁸F]FDG influx constant (K _i ) for the lungs was calculated using Patlak graphical analysis and an image derived blood input function. Nine animals per group were killed at 1, 7 and 28 days after exposure (n?=?3 per group and time point), and the lungs were harvested and submitted to immunohistochemical and histological analysis.

Results

Significantly higher mean whole-lung K _i values were obtained for animals exposed to NPs at days 1 and 7 after exposure (0.0045?±?0.0016 min^?1 and 0.0047?±?0.0015 min^?1, respectively) compared to controls (0.0024?±?0.0010 min^?1 and 0.0019?±?0.0011 min^?1 at 1 and 7 days, respectively). The K _i value for exposed animals dropped to 0.0023?±?0.0010 min^?1 at day 28. This value was not significantly different from the values obtained at 1, 7, and 28 days for the control group. Immunofluorescence staining on lung tissue slices from animals exposed to ZnO NPs showed an increase in CD11b reactivity at days 1 and 7, followed by a decrease in CD11b positive cells at 28 days. Hematoxylin–eosin staining showed histological alterations in the exposed lungs to ZnO NPs at days 1 and 7 that recovered at 28 days postexposure.

Conclusions

The [¹⁸F]FDG influx rate constant (K _i ) could be determined by PET using Patlak analysis and a corrected image derived input function. Higher K _i values were obtained for animals exposed to ZnO NPs at days 1 and 7 after exposition. These results were in good concordance with immunohistochemical assays performed on harvested tissue samples.     

Restricted Water Diffusibility as Measured by Diffusion-weighted MR Imaging and Choline Uptake in 11C-Choline PET/CT are Correlated in Pelvic Lymph Nodes in Patients with Prostate Cancer

Purpose

¹¹C-Choline-positron emission tomography (PET)/computed tomography (CT) is increasingly used in patients with prostate cancer. Another promising technique for assessment of tumor biology is diffusion-weighted MR imaging (DWI). The aim of the study was to compare the functional parameters standardized uptake value (SUV) in PET and apparent diffusion coefficient (ADC) value in DWI of lymph nodes in prostate cancer patients.

Procedures

Fourteen patients with prostate cancer underwent DWI at 1.5T and ¹¹C-Choline-PET/CT. ADC values and SUVs of all lymph nodes larger than 5 mm (n?=?55) were compared by using linear regression analysis. Performance of DWI and ¹¹C-Choline PET was assessed by receiver operator characteristic curve analysis using histopathology or clinical follow-up as standard of reference.

Results

ADC values and SUV showed a moderate but highly significant inverse correlation (r?=??0.5144, p?<?0.0001). In lymph nodes with low ADC values, the dispersion of SUV was more pronounced. Moreover, a highly significant difference was observed for mean ADC values and SUV in lymph nodes considered as benign or malignant by follow-up/histopathology (ADC 1.60?±?0.24 vs. 1.09?±?0.23?×?10^?3 mm²/s; SUV 1.82?±?0.57 vs. 4.68?±?03.12; p?<?0.0001, respectively).

Conclusion

These pilot data propose the ADC value in DWI as a new potential imaging biomarker which might provide additional information on tumor pathophysiology compared to the SUV in ¹¹C-Choline PET/CT.     

Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa

Purpose

Emergence of multidrug-resistant strains in intensive care units has renewed interest in colistin, which often remains the only available antimicrobial agent active against resistant Pseudomonas aeruginosa. The aim of this study is to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administration of colistin in piglets with pneumonia caused by P. aeruginosa.

Methods

In ventilated piglets, colistimethate was administered 24 h following bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration of colistin = 2 μg ml^?1) either by nebulization (8 mg kg^?1 every 12 h, n = 6) or by intravenous infusion (3.2 mg kg^?1 every 8 h, n = 6). All piglets were killed 49 h after inoculation. Colistin peak lung tissue concentrations and lung bacterial burden were assessed on multiple post mortem subpleural lung specimens.

Results

Median colistin peak lung concentration following nebulization was 2.8 μg g^?1 (25–75% interquartile range = 0.8–13.7 μg g^?1). Colistin was undetected in lung tissue following intravenous infusion. In the aerosol group, peak lung tissue concentrations were significantly greater in lung segments with mild pneumonia (median = 10.0 μg g^?1, 25–75% interquartile range = 1.8–16.1 μg g^?1) than in lung segments with severe pneumonia (median = 1.2 μg g^?1, 25–75% interquartile range = 0.5–3.3 μg g^?1) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts <10² cfu g^?1 following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts <10² cfu g^?1 49 h following bronchial inoculation.

Conclusion

Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.     

Green tea halts progression of cardiac transthyretin amyloidosis: an observational report

Background

Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy.

Methods

19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI (n?=?9) before and after consumption of GT and/or green tea extracts (GTE) for 12?months.

Results

Five patients were not followed up for reasons of death (n?=?2), discontinuation of GT/GTE consumption (n?=?2), and heart transplantation (n?=?1). After 12?months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (?12.5?%) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9?% in all 14 patients. Total cholesterol (191.9?±?8.9 vs. 172.7?±?9.4?mg/dL; p?p?Conclusions Our observation suggests an inhibitory effect of GT and/or GTE on the progression of cardiac amyloidosis. We propose a randomized placebo-controlled investigation to confirm our observation.     

Effect of transcatheter aortic valve implantation on the ascending aorta’s elasticity

Background

The elastic properties of the ascending aorta were studied before and 1?week after transcatheter aortic valve implantation (TAVI). Previous studies have shown that the distensibility of the ascending aorta was decreased in the early post-operative period after aortic valve replacement. Aortic stiffness is a major moderator of arterio-ventricular coupling and an independent predictor of cardiovascular risk and mortality. We evaluated the effect of TAVI on the elastic properties of the ascending aorta in the early post-operative period.

Methods

Aortic distensibility (AD) and Aortic Stiffness Index (ASI) were evaluated using echocardiographic techniques and brachial artery pressure obtained by sphygmomanometry 2–3?days before and 7–8?days after TAVI.

Results

A total of 30 patients (14 males) were studied with a mean age of 79.9?±?4.7?years and aortic valve area before TAVI of 0.61?±?0.16?cm². Mean arterial pressure decreased significantly after TAVI (from 89.6?±?8.9?mmHg to 83.3?±?10.9?mmHg, p?=?0.004). AD did not change significantly after TAVI (pre: 1.89?±?1.11?cm²/(dynes?×?10⁶), post: 2.05?±?1.50?cm²/(dynes?×?10⁶); p?=?0.813). ASI also remained unchanged (pre: 11.4?±?6.5, post: 15.6?±?14.9; p?=?0.349).

Conclusions

The elastic properties of the ascending aorta did not change significantly in the early post-procedural period after TAVI. This may in part be attributable to the less invasive procedure (compared to aortic valve replacement) which has no effect on vasa vasorum flow.     

Right ventricular ejection fraction is better reflected by transverse rather than longitudinal wall motion in pulmonary hypertension

Background

Longitudinal wall motion of the right ventricle (RV), generally quantified as tricuspid annular systolic excursion (TAPSE), has been well studied in pulmonary hypertension (PH). In contrast, transverse wall motion has been examined less. Therefore, the aim of this study was to evaluate regional RV transverse wall motion in PH, and its relation to global RV pump function, quantified as RV ejection fraction (RVEF).

Methods

In 101 PH patients and 29 control subjects cardiovascular magnetic resonance was performed. From four-chamber cine imaging, RV transverse motion was quantified as the change of the septum-free-wall (SF) distance between end-diastole and end-systole at seven levels along an apex-to-base axis. For each level, regional absolute and fractional transverse distance change (SFD and fractional-SFD) were computed and related to RVEF. Longitudinal measures, including TAPSE and fractional tricuspid-annulus-apex distance change (fractional-TAAD) were evaluated for comparison.

Results

Transverse wall motion was significantly reduced at all levels compared to control subjects (p < 0.001). For all levels, fractional-SFD and SFD were related to RVEF, with the strongest relation at mid RV (R² = 0.70, p < 0.001 and R² = 0.62, p < 0.001). For TAPSE and fractional-TAAD, weaker relations with RVEF were found (R² = 0.21, p < 0.001 and R² = 0.27, p < 0.001).

Conclusions

Regional transverse wall movements provide important information of RV function in PH. Compared to longitudinal motion, transverse motion at mid RV reveals a significantly stronger relationship with RVEF and thereby might be a better predictor for RV function.     

Direct Characterization of Arterial Input Functions by Fluorescence Imaging of Exposed Carotid Artery to Facilitate Kinetic Analysis

Purpose

With the goal of facilitating tracer kinetic analysis in small-animal planar fluorescence imaging, an experimental method for characterizing tracer arterial input functions is presented. The proposed method involves exposing the common carotid arteries by surgical dissection, which can then be imaged directly during tracer injection and clearance.

Procedures

Arterial concentration curves of IRDye-700DX-carboxylate, IRDye-800CW-EGF, and IRDye-800CW conjugated to anti-EGFR Affibody are recovered from athymic female mice (n?=?12) by directly imaging exposed vessels. Images were acquired with two imaging protocols: a slow-kinetics approach (temporal resolution?=?45 s) to recover the arterial curves from two tracers simultaneously, and a fast-kinetics approach (temporal resolution?=?500 ms) to characterize the first-pass peak of a single tracer. Arterial input functions obtained by the carotid imaging technique, as well as plasma curves measured by blood sampling were fit with a biexponential pharmacokinetic model.

Results

Pharmacological fast- and slow-phase rate constants recovered with the proposed method were 0.37?±?0.26 and 0.007?±?0.001 min^?1, respectively, for the IRDye700DX-C. For the IRDye800CW-EGF, the rate constants were 0.11?±?0.13 and 0.003?±?0.002 min^?1. These rate constants did not differ significantly from those calculated previously by blood sampling, as determined by an F test; however, the between-subject variability was four times lower for arterial curves recovered using the proposed technique, compared with blood sampling.

Conclusions

The proposed technique enables the direct characterization of arterial input functions for kinetic analysis. As this method requires no additional instrumentation, it is immediately deployable in commercially available planar fluorescence imaging systems.     

Does the surface-treated AN69 membrane prolong filter survival in CRRT without anticoagulation?

Purpose

The need for continuous anticoagulation remains a significant drawback in continuous renal replacement therapy (CRRT), especially in patients with increased bleeding risk. Polyethyleneimine treatment of the AN69 membrane (AN69ST) reduces thrombogenicity through decreased contact activation and promotion of heparin binding. The aim of this study is to evaluate whether this membrane prolongs filter survival in CRRT without anticoagulation.

Methods

A single-center, prospective, randomized, double-blind controlled trial with cross-over design comparing filter survival with the AN69ST membrane and the original AN69 membrane in 39 patients treated with continuous venovenous hemofiltraton (CVVH) without additional heparin.

Results

Filter survival with the AN69ST membrane (n?=?75) was 14.2?±?8.2?h, which is not significantly different from the 13.3?±?10.3?h for the original AN69 membrane (n?=?76; p?=?0.59). Limiting the analysis to those treatments that were interrupted for filter clotting yielded similar results: 14.4?±?8.2?h for the AN69 ST membrane (n?=?62) versus 14.1?±?7.5?h for the original AN69 membrane (n?=?56) (p?=?0.93).

Conclusions

Compared with the original AN69 membrane, the surface-treated AN69ST membrane does not prolong filter survival during CVVH without systemic anticoagulation and with the CRRT settings used in this study.