Comparison of the effects of adenosine, isoproterenol and their combinations on pulmonary transit time in rats using contrast echocardiography.

AIMS: To compare the effects of adenosine (Ade), isoproterenol (Iso) and their combinations on pulmonary transit time (PTT) in rats using contrast echocardiography. MATERIAL AND METHODS: Thirty-two adult Sprague Dawley (SD) rats were divided into four groups (n=8) according the medicines of tail-intravenous injection: Group 1, control; Group 2, Ade; Group 3, Iso; Group 4, Ade+Iso. They all underwent conventional echocardiography and contrast echocardiography with measurements of PTT. RESULTS: With Ade injection, OnsetRV-OnsetLV PTT (PTT1), PeakRV-PeakLV PTT (PTT2) and OnsetRV-PeakLV PPT (PTT3) decreased and PTT3 had the largest decreased percentage, with the highest performance in differentiating the Ade group from the control group [the area under receiver operating characteristic curve (AUC), sensitivity and Youden's index was maximal]. With Iso injection, PTT1, PTT2 and PTT1 all increased and PTT1 had the largest increased percentage, with the highest performance in differentiating the Iso group from the control group (AUC, sensitivity and Youden's index was maximal). With a combination injection of Ade and Iso, the PTT values were similar to the control group and no PTT coulddifferentiate the Ade+Iso group from the control group. CONCLUSIONS: Ade or/and Iso exerted distinct effects on PTT. These findings remind us that it is a necessary to consider the effects of medicine (especially cardiopulmonary vasoactive drugs) on the PTT values. At the same time, it provides the basis for the clinical transformation of consecutive Iso/Ade treatment from the perspective of pulmonary circulation.

A novel application of pulmonary transit time to differentiate between benign and malignant pulmonary nodules using myocardial contrast echocardiography.

Malignant pulmonary nodules (PNs) are often accompanied by vascular dilatation and structural abnormalities. Pulmonary transit time (PTT) measurement by contrast echocardiograghy has used to assess the cardiopulmonary function and pulmonary vascular status, such as hepatopulmonary syndrome and pulmonary arteriovenous fistula, but has not yet been attempted in the diagnosis and differential diagnosis of PNs. The aim of this work was to evaluate the feasibility and performance of myocardial contrast echocardiography (MCE) for differentiating malignant PNs from benign ones. The study population consisted of 201 participant: 66 healthy participants, 65 patients with benign PNs and 70 patients with malignant PNs. Their clinical and conventional echocardiographic characteristics were collected. MCE with measurements of PTT were performed. There was no difference in age, sex, heart rate, blood pressure, smoking rate, background lung disease, pulmonary function, ECG, myocardial enzymes, cardiac size and function among the healthy participant, patients with benign and malignant PNs (P > 0.05). PTT did not differ significantly in patients with PNs of different sizes, nor did they differ in patients with PNs of different enhancement patterns (P > 0.05). However, the PTT were far shorter (about one half) in patients with malignant PNs than in patients with benign ones (1.88 ± 0.37 vs. 3.73 ± 0.35, P < 0.001). There was no significantly different between patients with benign PNs and healthy participant (3.73 ± 0.35 vs.3.89 ± 0.36, P > 0.05). The area under the receiver operating characteristics curve (AUC) of PTT was 0.99(0.978-1.009) in discriminating between benign and malignant PNs. The optimal cutoff value was 2.78 s, with a sensitivity of 98.52%, a specificity of 97.34%, and a accuracy of 97.69%. MCE had a powerful performance in differentiating between benign and malignant PNs, and a pulmonary circulation time of < 2.78 s indicated malignant PNs.

Coronary sinus flow is reduced in methamphetamine abusers: a transthoracic echocardiographic study.

To compare the coronary sinus flow among healthy participants, methamphetamine abusers without chest pain and those with chest pain. One hundred and eight methamphetamine abusers: 53 ones without chest pain, 55 ones with chest pain, free of ascertained coronary artery disease, were enrolled in this study. A control group of 50 age-matched male healthy participants was studied for comparison. Standard 2D, flow and tissue Doppler echo with measurements of cardiac morphologic and functional indicators, coronary sinus flow, and inferior vena cava (IVC) ultrasound with measurements of the IVC dimensions and their collapsibility index were performed, respectively. Compared to healthy participants, methamphetamine abusers had higher blood pressure, greater left ventricular mass index and more impaired diastolic function, with preserved cardiac sizes, systolic function and right atrial pressure. Methamphetamine abusers with chest pain had faster heart rate than those without chest pain and healthy participants. Coronary sinus flow was significantly less in methamphetamine abusers than in healthy participants (P < 0.05), and was extremely lower in those with chest pain than in healthy participants (about one-fourth) (P < 0.01). The area under the curve (AUC) of coronary sinus flow was 0.913 (0.864-0.962), and the cutoff value with 221.65 mL/min had sensitivity of 83.4%, specificity of 87.2% and accuracy of 85.2% for differentiating methamphetamine abusers from healthy participants. While the AUC of coronary sinus flow was 0.996 (0.989-1.003), and the cutoff value with 172.59 mL/min had sensitivity of 100%, specificity of 93.3% and accuracy of 96.5% for predicting methamphetamine abusers with chest pain. Coronary sinus flow is significant reduced in methamphetamine abusers, which is maybe a good indicator for indentifying methamphetamine abusers from normal population, and for predicting methamphetamine abusers with chest pain.

The safety and feasibility of diagnostic acoustic radiation force impulse elastography used for eyes. A preliminary in vivo study.

AIMS: To assess the safety and feasibility of acoustic radiation force impulse (ARFI) elastography in the eyes of rats. Material and methods: One hundred and twenty-six SD rats were divided into 7 groups. Group 1 was the control group and Group 2 to Group 7 were investigated by ARFI elastography using increased powers of 5%, 10%, 20%, 50%, and 100% and repetitions of 5 or 10. The changes of ocular architecture structures and functions were examined by phthalmoscopic, histopathologic, and light reflex examination, and the expression level of IL-6, IL-8, and TNF-α was determined in days 1, 3, and 7 after ARFI elastography, respectively. RESULTS: A satisfactory ARFI elastography was obtained in all SD rats. The shear wave velocity (SWV) values of soft tissues behind the eyeball were significantly greater than those of the eyes (1.89±0.95 vs. 0.84±0.36 m/s, p<0.05). The SWV values of eyes and the soft tissues behind the eyeball did not differ among any groups at any time-point (p>0.05). The SD rats of each group showed good light perception, pupillary light reflex, and avoidance reaction induced by the sudden bright light from the dark environment at any time. In each group, ocular architecture structures were well preserved, and with a normal expression level of IL-6, IL-8, and TNF-α (p>0.05). CONCLUSIONS: Diagnostic ARFI elastography is a safe and feasible ultrasonic imaging mode and may potentially be applied for human eyes in its present form.

An immunohistochemical analysis of a rat model of proliferative vitreoretinopathy and a comparison of the expression of TGF-ß and PDGF among the induction methods.

Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment surgery or ocular trauma. Our previous study indicated that intravitreal co-injection of retinal pigmented epithelial (RPE)-J cells and platelet-rich plasma (PRP) (not RPE-J cells or PRP alone) in Wistar rat eyes can successfully induce a model of PVR. But which cells are involved in this process and why different induction methods, intravitreal injection of RPE-J cells or/and PRP, induced a different situation remain to be unknown. In this study, immunohistochemistry was performed to identify the main cell types involved in this process. The expression levels of transforming growth factor (TGF)-ß2, platelet-derived growth factor (PDGF)-AA and PDGF-BB were tested using enzyme-linked immunosorbent assay (ELISA). The results showed that RPE cells, glial cells, fibroblasts and macrophages took part in the pathogenesis of this model. The expression levels and durations of TGF-ß2 and PDGF-BB partially explained the different results induced by the different induction methods. This provides an experimental proof for attenuation of the experimental PVR by targeting at a specific cells or growth factor.

Comparative analysis of gene transfer to human and rat retinal pigment epithelium cell line by a combinatorial use of recombinant adeno- associated virus and ultrasound or/and microbubbles.

Ultrasound-targeted microbubble destruction has been utilized to deliver a drug/gene into cells in both in vitro and in vivo studies. This work was performed to investigate the feasibility of gene transfer to human retinal pigment epithelium cell line(ARPE-19) and rat retinal pigment epithelium cell line(RPE-J) by a combinatorial use of recombinant adeno-associated virus (rAAV) and ultrasound (US) or/and microbubbles (MBs) and compare the difference between them. Different doses of serotype 2 rAAV encoding a enhanced green fluorescent protein (rAAV2-EGFP) gene and MBs was administered to ARPE-19 and RPE-J cells under different US conditions. Transfection efficiency and cell viability were assessed by fluorescence microscopy, flow cytometry (FCM) analysis, trypan blue staining. The results indicated that US and MBs could respectively improve rAAV2-mediated gene transfer to RPE-J cells, but neither US nor MBs could do so in ARPE-19 cells. US plus MBs could significantly enhance rAAV2-mediated gene transfer to ARPE-19 cells, however, the same effects were not seen in RPE-J cells. These findings demonstrated it is not always coincident that US, MBs and US plus MBs exert the similar effects on gene transfer in vitro RPE cells. So, it is necessary to choose appropriate RPE cell line for the study of US or/and MBs-mediated rAAV gene transfer in retinal gene therapy.

Comparative analysis of the effects of ultrasound-targeted microbubble destruction on recombinant adeno-associated virus- and plasmid-mediated transgene expression in human retinal pigment epithelium cells.

Ultrasound-targeted microbubble destruction (UTMD) has been utilized to deliver a drug/gene into cells in both in vitro and in vivo studies. This study was performed to investigate the feasibility of UTMD-enhanced recombinant adeno-associated virus- (rAAV) and plasmid-mediated transfection into the human retinal pigment epithelium (RPE) cell line ARPE-19. Additionally, the transfection efficiency of rAAV and plasmid was compared in order to choose the appropriate gene vector or strategy to be used with UTMD for RPE-based gene modification. rAAV or plasmid encoding an enhanced green fluorescent protein gene was administered to ARPE-19 cells under various UTMD conditions. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide (MTT) assay. Transfection efficiency was determined by fluorescence microscopy and flow cytometry. UTMD significantly enhanced the transfection efficiency of rAAV and plasmid in ARPE-19 cells without adverse effects on cell viability. The transfection efficiency of rAAV was higher than that of plasmid. rAAV is therefore an appropriate gene vector for use with UTMD in retinal gene modification.