Estimated Functional Diameter of Alveolar Septal Microvessels at the Zone I‐II Border

Conhai, Robert L.; Rodenkirch, Lance A.

doi:10.3109/10739689709148317

Cited by 9 publications

(11 citation statements)

References 13 publications

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“…Previous study on large microbubbles revealed that they coalesced in the capillary and subsequently to shrink to flow through or collapse[36]. Most microbubbles larger than 10 μm will be filtered by the pulmonary capillary[21] in consistent with our microscopic image of the microbubbles after passing through the grade 595 1/2 filter paper (Fig 3A and Fig 3B). In our study, all the mice are well tolerated with the size of the microbubbles showing no observable heart distress.…”

Section: Discussionsupporting

confidence: 86%

“…The ultrasound generates inertial cavitation improving the permeability of cell membranes and enabling extracellular molecules transport directly into the cytosol[20]. In addition, large microbubbles with diameter more than 10 μm will collapse and release its contents into lung capillary bed leading to the lung targeted release[21]. Animal studies have shown that these microbubbles don't affact hemodynamic and flow at similar velocity as red blood cells if they are injected into a peripheral vein[22,23] Thus a combination of microbubbles with conventional jetPEI for gene silencing in vivo tends to be highly interested.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis

Zha

Xie

et al. 2017

PLoS ONE

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Pleiotrophin (PTN) is a secreted cytokine that is expressed in various cancer cell lines and human tumor such as colon cancer, lung cancer, gastric cancer and melanoma. It plays significant roles in angiogenesis, metastasis, differentiation and cell growth. The expression of PTN in the adult is limited to the hippocampus in an activity-dependent manner, making it a very attractive target for cancer therapy. RNA interference (RNAi) offers great potential as a new powerful therapeutic strategy based on its highly specific and efficient silencing of a target gene. However, efficient delivery of small interfering RNA (siRNA) in vivo remains a significant hurdle for its successful therapeutic application. In this study, we first identified, on a cell-based experiment, applying a 1:1 mixture of two PTN specific siRNA engenders a higher silencing efficiency on both mRNA and protein level than using any of them discretely at the same dose. As a consequence, slower melanoma cells growth was also observed for using two specific siRNA combinatorially. To establish a robust way for siRNA delivery in vivo and further investigate how silence of PTN affects tumor growth, we tested three different methods to deliver siRNA in vivo: first non-targeted in-vivo delivery of siRNA via jetPEI; second lung targeted delivery of siRNA via microbubble coated jetPEI; third tumor cell targeted delivery of siRNA via transferrin-polyethylenimine (Tf-PEI). As a result, we found that all three in-vivo siRNAs delivery methods led to an evident inhibition of melanoma growth in non-immune deficiency C57BL/6 mice without a measureable change of ALT and AST activities. Both targeted delivery methods showed more significant curative effect than jetPEI. The lung targeted delivery by microbubble coated jetPEI revealed a comparable therapeutic effect with Tf-PEI, indicating its potential application for target delivery of siRNA in vivo.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis

Zha

Xie

et al. 2017

PLoS ONE

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“…Upon peripheral intravenous injection, most of them can pass through the lung. Any microbubbles larger than 10 μm will be filtered by the lung capillary bed (12). Animal studies have shown that these microbubbles flow at approximately the same velocity as red blood cells, and they do not alter hemodynamics if they are injected into a peripheral vein (13, 14).…”

mentioning

confidence: 99%

In vivo study of microbubbles as an MR susceptibility contrast agent

Wong

Huang

Kim

et al. 2004

Magnetic Resonance in Med

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The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison®, was studied with rat liver imaging at 7 T. Optison® suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (⌬R 2 *) of 29.1 ؎ 1.6 s -1 (N ‫؍‬ 2) and 61.5 ؎ 12.9 s -1 (N ‫؍‬ 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO 2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro ⌬R 2 * measurements of Optison® suspension at different concentrations are also reported. Magn Reson Med 52:445-452, 2004.

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“…In a subsequent report (3), we estimated the functional diameter of these vessels in zone I to be 1.7 µm. When we raised the pulmonary arterial pressure (Ppa) to equal the inflation pressure (zone I/II border), we estimated that the microvessel diameter would increase to 6-8 µm (4).…”

mentioning

confidence: 99%

Functional diameters of alveolar microvessels at high lung volume in zone II

Conhaim

Rodenkirch

1998

Journal of Applied Physiology

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To estimate the functional diameter of alveolar microvessels, we perfused isolated rat lungs with fluorescent latex particles (1 diameter/lung) at inflation, pulmonary arterial, and left atrial pressures of 25, 30, and 0 cmH2O, respectively. We used confocal microscopy to count latex particles within septal microvessels and flow cytometry to count particle concentrations in venous outflow. We found 1-, 2-, and 4-micron-diameter particles within septal vessels of 45 +/- 12, 31 +/- 12, and 25 +/- 9%, respectively, of examined alveoli. Particles of 5-micron diameter were absent from septal vessels but were present within a small percentage of corner vessels. Particle concentrations in the venous outflow for 1-, 2-, 4-, and 5-micron-diameter particles were 54 +/- 28, 67 +/- 32, 2.2 +/- 0.3, and 0.4 +/- 0.3%, respectively, of the arterial inflow. Particles with diameters of 6 or 10 micron were absent from venous outflow. Our results suggest that, under these conditions, the functional diameter of the septal microvessels is approximately 4 micron and that the diameter of the adjacent corner vessels is slightly larger but <6 micron.

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Estimated Functional Diameter of Alveolar Septal Microvessels at the Zone I‐II Border

Abstract: In a previous study, conducted at the same value of Pinflat, but with PPA set at 15 or 20 (5 or 10 cm H2O into zone I). We estimated the capillary diameter to be 1.7 microns. Thus, the septal capillary diameter seems to increase by three- to fourfold as PPA is raised to equal Pinflat.

Cited by 9 publications

References 13 publications

Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis

Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis

In vivo study of microbubbles as an MR susceptibility contrast agent

Functional diameters of alveolar microvessels at high lung volume in zone II

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