Perfusion Computer Tomography Assessment of the Effect of Angiotensin II On Blood Flow Distribution in Rabbits with Intrarenal VX2 Tumors.

BACKGROUND/AIMS: Unlike other organs, which only have one set of capillary network, the renal microvasculature consists of two sets of capillary network series connected by efferent arterioles. Angiotensin II constricts the efferent glomerular artery. Hence, renal tumor blood flow (BF) distribution may be different from tumors in other organs. This study aims to investigate the effects of angiotensin II on the hemodynamics of intrarenal VX2 tumors using perfusion computed tomography(CT). METHODS: Twenty-four male New Zealand white rabbits were randomly divided into three groups: groups A (blank controls), group B (negative controls), and group C (angiotensin II-treated animals). Group B and C were established to the model of intrarenal VX2 tumors. Furthermore, perfusion CT of the kidney was performed in each group. Prior to perfusion CT scan in group C, the mean arterial blood was elevated to 150-160 mmHg by angiotensin II. The BF, blood volume (BV), mean transit time (MTT), capillary permeability-surface area product (PS), and relative permeability-surface area product (RPS) of tumors and renal tissues were calculated. RESULTS: Compared with normal renal cortex tissues in group A, the BF, BV and PS values of tumors in group B were significantly lower, MTT was prolonged and RPS increased. Compared with group B, only the RPS of these tumors increased from 83.23 ± 29.17% to 120.94 ± 31.84% by angiotensin II infusion. Angiotensin II significantly increased the RPS value of the renal cortex distant from the tumor (CDT) and the right renal cortex (RRC). CONCLUSIONS: Perfusion CT can accurately observe the influence of angiotensin II on normal and tumor BF in kidneys. This clarifies the effect of angiotensin II on intrarenal tumor hemodynamics.

Morphometric and hemodynamic analysis of atherosclerotic progression in human carotid artery bifurcations.

Although atherosclerosis has been widely investigated at carotid artery bifurcation, there is a lack of morphometric and hemodynamic data at different stages of the disease. The purpose of this study was to determine the lesion difference in patients with carotid artery disease compared with healthy control subjects. The three-dimensional (3D) geometry of carotid artery bifurcation was reconstructed from computed tomography angiography (CTA) images of Chinese control subjects (n = 30) and patients with carotid artery disease (n = 30). We defined two novel vector angles (i.e., angles 1 and 2) that were tangential to the reconstructed contour of the 3D vessel. The best-fit diameter was computed along the internal carotid artery (ICA) center line. Hemodynamic analysis was performed at various bifurcations. Patients with stenotic vessels have larger angles 1 and 2 (151 ± 11° and 42 ± 20°) and smaller diameters of the external carotid artery (ECA) (4.6 ± 0.85 mm) compared with control subjects (144 ± 13° and 36 ± 16°, 5.2 ± 0.57 mm) although there is no significant difference in the common carotid artery (CCA) (7.1 ± 1.2 vs. 7.5 ± 1.0 mm, P = 0.18). In particular, all patients with carotid artery disease have a stenosis at the proximal ICA (including both sinus and carina regions), while 20% of patients have stenosis at the middle ICA and 20% have stenosis expansion to the entire cervical ICA. Morphometric and hemodynamic analyses suggest that atherosclerotic plaques initiate at both sinus and carina regions of ICA and progress downstream.

A Photothermal Therapy Strategy for Monitoring Real-Time Temperature in Kidney Cancers by Injecting Gold Nanorods with Phosphors.

Photothermal ablation therapy (PTA) has been widely reported; however, it is not possible to predict the internal temperature of the tumor in real time that causes ineffective treatment and normal tissue burns. Here, we have designed a photothermal therapy strategy under real-time temperature monitoring by injecting gold nanorods (AuNRs) and NaYF4: Yb3+ /Er3+ into the tumor site where AuNRs are used for PTA of cancer cells by converting the absorbed energy into heat and using Yb3+ , Er3+-NaYF 4 phosphors to monitor the temperature inside the tumor. Our experiments confirm the effectiveness of this strategy, which is expected to be an aid in the development of real-time temperature monitoring and effective photothermal therapy for the treatment of cancers.

Inhalation of Ultrafine Zinc Particles Impaired Cardiovascular Functions in Hypertension-Induced Heart Failure Rats With Preserved Ejection Fraction.

Although it is possible for inhalation of ultrafine particles to impair human health, its effect is not clear in patients with HFpEF. This study investigated cardiac and hemodynamic changes in hypertension-induced rats of HFpEF after inhaling ultrafine zinc particles for a while. Multiple experimental measurements were carried out in DSS rats fed with high salt (HS) and low salt (LS) diets as well as HS diet with the inhalation of ultrafine zinc particles (defined as HP). Cardiac strain and strain rate were quantified by the speckle tracking echocardiography. The pressure and flow waves were recorded in the carotid artery and abdominal aorta and analyzed by the models of Windkessel and Womersley types. HS and HP rats were found to show lower strains on endocardium and epicardium than LS rats. The inhalation of ultrafine zinc particles further reduced the strain in the longitudinal direction on the endocardium of rats with HFpEF, but had relatively small effects on the epicardium. The inhalation of ultrafine zinc particles resulted in the increase of systemic resistance and the decrease of total vascular compliance as well as the increased PWV and induced more severe vascular stiffening in rats with HFpEF. In summary, the inhalation of ultrafine zinc particles deteriorated local myocardial dysfunctions in the LV and the hemodynamic environment in peripheral arteries in rats of HFpEF. This study is of importance to understand the mechanisms of cardiovascular impairments owing to air pollution.

Surface-adaptive zwitterionic nanoparticles for prolonged blood circulation time and enhanced cellular uptake in tumor cells.

Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(ß-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanoparticles without compromising their long circulating capability, providing a practical method for improving the tumor-targeting efficiency of particulate drug delivery systems. STATEMENT OF SIGNIFICANCE: Herein we demonstrate a general strategy to integrate non-fouling zwitterionic surface on the nanoparticles without compromising their capability of tumor accumulation, by constructing a surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(ß-amino ester) (PAE) heterogeneous surfaces. At the blood pH (7.4), PAE chains collapsed to the inner of the shell due to the deprotonation, and the forming micro-phase separation structure was synergistic with zwitterionic surface to prolong the circulation time of MSMs in the blood. While at the tumor sites, PAE was protonated, and the positively charged surface of MSMs enhanced cellular uptake. This self-assembly-based strategy is compatible to other zwitterionic materials, endowing a great flexibility for the construction of responsive drug delivery systems particularly to the novel chemotherapeutic agents.

The Structure-function remodeling in rabbit hearts of myocardial infarction.

Animal models are of importance to investigate basic mechanisms for ischemic heart failure (HF). The objective of the study was to create a rabbit model through multiple coronary artery ligations to investigate the postoperative structure-function remodeling of the left ventricle (LV) and coronary arterial trees. Here, we hypothesize that the interplay of the degenerated coronary vasculature and increased ventricle wall stress relevant to cardiac fibrosis in vicinity of myocardial infarction (MI) precipitates the incidence and progression of ischemic HF Echocardiographic measurements showed an approximately monotonic drop of fractional shortening and ejection fraction from 40% and 73% down to 28% and 58% as well as persistent enlargement of LV cavity and slight mitral regurgitation at postoperative 12 weeks. Micro-CT and histological measurements showed that coronary vascular rarefaction and cardiac fibrosis relevant to inflammation occurred concurrently in vicinity of MI at postoperative 12 weeks albeit there was compensatory vascular growth at postoperative 6 weeks. These findings validate the proposed rabbit model and prove the hypothesis. The post-MI rabbit model can serve as a reference to test various drugs for treatment of ischemic HF.

Growth, ageing and scaling laws of coronary arterial trees.

Despite the well-known design principles of vascular systems, it is unclear whether the vascular arterial tree obeys some scaling constraints during normal growth and ageing in a given species. Based on the micro-computed tomography measurements of coronary arterial trees in mice at different ages (one week to more than eight months), we show a constant exponent of 3/4, but age-dependent scaling coefficients in a length-volume scaling law (Lc=K(length-volume) · Vc³/4; Lc is the crown length, Vc is the crown volume, K(length-volume) is the age-dependent scaling coefficient) during normal growth and ageing. The constant 3/4 exponent represents the self-similar fractal-like branching pattern (i.e. basic mechanism to regulate the development of vascular trees within a species), whereas the age-dependent scaling coefficients characterize the structural growth or resorption of vascular trees during normal growth or ageing, respectively. This study enhances the understanding of age-associated changes in vascular structure and function.