scholarly journals Safety study of malapposition of the bio-corrodible nitrided iron stent in vivo

2021 ◽  
Vol 10 (1) ◽  
pp. 839-846
Author(s):  
Xiaoli Shi ◽  
Jin Wang ◽  
Gui Zhang ◽  
Lu Zhang ◽  
Wanqian Zhang ◽  
...  

Abstract To evaluate the safety of stent malapposition of corrodible nitride iron stent as biodegradable cardiovascular implants, a total of 108 stents were implanted into the abdominal aortas, iliac arteries, and iliac artery bifurcations of 36 New Zealand white rabbits separately. Each rabbit was implanted with three stents. After a follow-up period of 3 months, no thrombus and embolism were found in local and downstream vessels. And no other adverse events occurred either. Stent strut covered by endothelial layer started to show signs of degradation, while struts exposed to bifurcated blood flow covered by a layer of tissue and no rust particle was found on the surface. Also, there were no traces of thrombosis and traces of excess inflammation. The authors conclude that the risk brought by stent malapposition in less than 9 months is acceptable.

2021 ◽  
pp. neurintsurg-2020-017261
Author(s):  
Stefan Wanderer ◽  
Basil Erwin Grüter ◽  
Fabio Strange ◽  
Gwendoline Boillat ◽  
Sivani Sivanrupan ◽  
...  

BackgroundAneurysm wall degeneration is linked to growth and rupture. To address the effect of aspirin (ASA) on aneurysm formation under various wall conditions, this issue was analyzed in a novel rabbit bifurcation model.MethodsBifurcation aneurysms created in 45 New Zealand White rabbits were randomized to vital (n=15), decellularized (n=13), or elastase-degraded (n=17) wall groups; each group was assigned to a study arm with or without ASA. At follow-up 28 days later, aneurysms were evaluated for patency, growth, and wall inflammation at macroscopic and histological levels.Results36 rabbits survived to follow-up at the end of the trial. None of the aneurysms had ruptured. Patency was visualized in all aneurysms by intraoperative fluorescence angiography and confirmed in 33 (92%) of 36 aneurysms by MRI/MRA. Aneurysm size was significantly increased in the vital (without ASA) and elastase-degraded (with and without ASA) groups. Aneurysm thrombosis was considered complete in three (50%) of six decellularized aneurysms without ASA by MRI/MRA. Locoregional inflammation of the aneurysm complex was significantly reduced in histological analysis among all groups treated with ASA.ConclusionASA intake prevented inflammation of both the periadventitial tissue and aneurysm wall, irrespective of initial wall condition. Although ASA prevented significant growth in aneurysms with vital walls, this preventive effect did not have an important role in elastase-degraded pouches. In possible translation to the clinical situation, ASA might exert a potential preventive effect during early phases of aneurysm formation in patients with healthy vessels but not in those with highly degenerative aneurysm walls.


2020 ◽  
Author(s):  
Juejun Liu ◽  
Changzheng Chen ◽  
Lu Li ◽  
Yishuang Xu ◽  
Zuohuizi Yi ◽  
...  

Abstract Background: Optical coherence tomography angiography (OCTA) is a principally new imaging technique that provide quantitative method to analyze choriocapillaris (CC) flow changes, while assessment of CC in vivo could be valuable in understanding the pathological mechanism of chronic central serous chorioretinopathy (CCSC) and the therapeutic effects of photodynamic therapy (PDT). In this study, we sought to quantify blood flow changes in CC of CCSC patients receiving half-dose PDT using OCTA.Methods: A total of 28 affected eyes and 24 unaffected eyes of 26 CCSC patients receiving half-dose PDT, and 40 eyes of 20 healthy gender- and age-matched subjects were retrospectively enrolled. The proportion of total areas of flow signal voids (FSV, %) in CC level of OCTA was assessed in both eyes of the CCSC patients at baseline and repeated in multiple sections at 1-week, 1-month, 3-month and 6-month intervals after PDT. In addition, CC patterns in response to PDT at early stage and their subsequent morphologic changes were qualitatively documented using OCTA. Results: For affected eyes, significant decrease in FSV was found at 6-m follow-up when compared with that at 1-m follow-up (p=0.036). When compared to normal control eyes, FSV in affected eyes was significantly higher at 1-m, 3-m and 6-m follow-up (p<0.05 for all), while FSV in unaffected eyes was significantly higher at baseline, 1-w, 1-m and 3-m follow-up (p<0.05 for all). Three CC patterns of early response to PDT were identified, including signs of recovery with more even flow signals, transient appearance of worse ischemia and secondary neovascularization within CC level.Conclusion: Abnormal CC flow attenuation remains in completely resolved eyes of CCSC patients treated with half-dose PDT.


1993 ◽  
Vol 16 (4) ◽  
pp. 218-228 ◽  
Author(s):  
S.D. Shefer ◽  
J. Ferreira ◽  
C. J-P. Mullon ◽  
R. Langer

An extracorporeal circuit incorporating a plasma separator reactor (PSR) was designed to modify low density lipoproteins (LDL). The PSR was tested in vivo with hypercholesterolemic New Zealand White rabbits. The bioreactor enzymatically converts LDL to a form that can be removed by the body at an enhanced rate. The physiological response of hypercholesterolemic New Zealand White rabbits to 90 minute extracorporeal treatments was monitored. The total plasma cholesterol concentration in the treated rabbits fell sharply (up to 40% decrease) during and following the treatment. Results of safety tests indicate no significant enzyme leaching from the device, no disruption or damage to erythrocytes, no increase in white blood cell count and no liver damage as indicated by five enzyme assays. All safety measurements suggest that the treatment is safe.


1988 ◽  
Vol 65 (2) ◽  
pp. 706-713 ◽  
Author(s):  
V. B. Antony ◽  
C. L. Owen ◽  
D. English

Injection of phorbol 12-myristate 13-acetate (PMA) into polymorphonuclear leukocyte (PMN)-depleted, PMN cytoplast-repleted New Zealand White rabbits caused the development of acute lung injury in vivo. PMN cytoplasts are nucleus- and granule-free vesicles of cytoplasm capable of releasing toxic O2 radicals but incapable of releasing granule enzymes. PMN cytoplasts when activated by PMA reduced 66 +/- 12.7 nmol of cytochrome c compared with 2.6 +/- 0.7 nmol in their resting state and did not release a significant quantity of granule enzymes (P greater than 0.05). Injection of PMA into New Zealand White rabbits caused a significant decrease (P less than 0.05) in the number of circulating cytoplasts. Increases in lung weight-to-body weight ratios in PMA-treated rabbits (9.8 +/- 0.5 X 10(-3] compared with saline-treated rabbits (5.3 +/- 0.2 X 10(-3] were also noted. Levels of angiotensin-converting enzyme in lung lavage as well as the change in alveolar-arterial O2 ratio correlated with the numbers of cytoplasts in lung lavage (P = 0.001, r = 0.84 and P = 0.0166, r = 0.73, respectively). Albumin in lung lavage increased to 1,700 +/- 186 mg/ml in PMA-treated rabbits from 60 +/- 30 mg/ml in saline-treated rabbits. These changes were attenuated by pretreatment of rabbits with dimethylthiourea (DMTU). In vitro, cytoplasts were able to mediate increases in endothelial monolayer permeability. This was evidenced by increases in fractional transit of albumin across endothelial monolayers when treated with PMA-activated cytoplasts (0.08 +/- 0.01 to 0.28 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Lea J Sayce ◽  
Maria E Powell ◽  
Emily E Kimball ◽  
Patty Chen ◽  
Gary J Gartling ◽  
...  

New Zealand white rabbits (Oryctolagus cuniculus) are an established in vivo model for the study of structural and functional consequences of vocal-fold vibration. Research design requires invasive laryngotracheal procedures, and the presence of laryngospasms or pain responses (or both) hinder phonation-related data collection. Published anesthesia regimens report respiratory depression and muscle tone changes and have been unsuccessful in mitigating autonomic laryngeal responses in our protocol. Infusion of ketamine hydrochloride and dexmedetomidine hydrochloride in pediatric medicine provides effective analgesia and sedation for laryngotracheal procedures including intubation and bronchoscopy; however, data evaluating the use of ketamine–dexmedetomidine infusion in rabbits are unavailable. This study reports a new infusion regimen, which was used in 58 male New Zealand white rabbits that underwent a nonsurvival laryngotracheal procedure to induce phonotraumatic vocal-fold injury. Animals were sedated by using ketamine hydrochloride (20 mg/kg IM) and dexmedetomidine (0.125 mg/kg IM). Maintenance anesthesia was provided by using continuous rate intravenous infusion of ketamine hydrochloride (343 μg/kg/min) and dexmedetomidine (1.60 μg/kg/min). A stable plane of anesthesia with no autonomic laryngeal response (laryngospasm) was achieved in 32 of the 58 rabbits (55%). Laryngospasms occurred in 25 of 58 animals (43%) and were controlled in 20 cases (80%) by providing 0.33 mL 2% topical lidocaine, incremental increase in infusion rate, or both. Continuous rate infusion of ketamine hydrochloride–dexmedetomidine with prophylactic topical lidocaine provides a predictable and adjustable surgical plane of anesthesia, with minimal confounding respiratory and autonomic laryngeal responses, during extended-duration laryngotracheal surgery in rabbits. This regimen should be considered as an alternative to injection maintenance for prolonged, invasive procedures.


2019 ◽  
Vol 133 (7) ◽  
pp. 869-884 ◽  
Author(s):  
Xianglan Liu ◽  
Ruoxi Zhang ◽  
Jingbo Hou ◽  
Jian Wu ◽  
Maomao Zhang ◽  
...  

Abstract Background: Early strut coverage after sirolimus-eluting stent (SES) implantation is associated with the activation of inflammation, but the underlying mechanisms are not completely understood. The present study aimed to identify the relationship between the anti-inflammatory cytokine interleukin (IL) 35 (IL-35) and early strut coverage in vivo and in vitro. Methods: We utilized a retrospective study design to measure IL-35 levels in 68 stents from 68 patients with coronary artery disease and recorded serial optical coherence tomography (OCT) images (0 and 3 months) to assess stent endothelialization. The mechanism underlying the regulatory effects of IL-35 on macrophages and human umbilical vein endothelial cells (HUVECs) was also investigated. SESs were surgically implanted into the right common carotid arteries of 200 male New Zealand White rabbits receiving intravenous injections of IL-35 or a placebo. Results: At the 3-month OCT evaluation, complete endothelium coverage was correlated with IL-35 levels. IL-35 induced the activation of an anti-inflammatory M2-like macrophage phenotype by targeting the signal transducer and activators of transcription (STAT)1/4 signalling pathway, and IL-35-treated macrophages induced endothelial proliferation and alleviated endothelial dysfunction. IL-35-treated New Zealand White rabbits with implanted SESs showed lower percentages of cross-sections with an uncovered strut, elevated mean neointimal hyperplasia (NIH) thickness, and inhibited inflammatory responses. Conclusions: We investigated the effect of IL-35 expression on early stent endothelialization in vivo and in vitro and identified a crucial role for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype. The present study highlights a new therapeutic strategy for early stent endothelialization.


1997 ◽  
Vol 272 (6) ◽  
pp. H2701-H2707 ◽  
Author(s):  
G. Nickenig ◽  
O. Jung ◽  
K. Strehlow ◽  
O. Zolk ◽  
W. Linz ◽  
...  

Low-density lipoprotein increases the AT1-receptor gene expression in vascular smooth muscle cells. To elucidate whether elevated cholesterol serum levels upregulate the AT1 receptor and its functional response to angiotensin II in vivo, we compared 1) the vasoconstrictive effect of angiotensin II and 2) the level of expression of the vascular AT1 receptor in aortas of normocholesterolemic and hypercholesterolemic rabbits. Contraction experiments on isolated aortic rings showed that the angiotensin II-induced vasoconstriction was increased in hypercholesterolemic New Zealand White rabbits compared with normocholesterolemic New Zealand White rabbits. This difference in the angiotensin II-induced vasoconstriction was caused by a twofold increase in the density of cell surface AT1 receptors in hypercholesterolemic rabbits, as assessed by radioligand binding assays. The enhanced expression of AT1 receptors on the surface of these vascular cells was caused by elevated steady-state levels of the AT1-receptor mRNA to 220 +/- 35% in aortas excised from hypercholesterolemic rabbits compared with levels in aortas from normocholesterolemic rabbits, as measured by Northern blot analysis. These data indicate that hypercholesterolemia is associated with upregulation of expression and function of vascular AT1 receptors in vivo. This suggests a novel mechanism by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis if the phenomenon is confirmed in humans.


1987 ◽  
Author(s):  
R Edwards ◽  
W Brande

Bacterial 1ipopolysaccharide (LPS) ts a potent stimulus for monocyte tissue factor (MTF) generation jn. vitro. We have examined the effect of small amounts of LPS on MTF expression in vivo. LPS (0.1 - 50ug) was injected into the ear veins of 66 New Zealand White rabbits. Arterial blood was collected immediately prior to LPS (TO), and 5 (T5) and 30 (T30) minutes later. Mononuclear cell suspensions (MC) were assessed for monocyte (Mo) content and MTF generation was determined in both unstimulated and LPS-stimulated MC cultures (18 hours incubation). As seen in the table, T5 cells obtained following in vivo exposure to 5 or lOug LPS demonstrated spontaneous MTF generation in the absence of in vitro stimulation. By T30, the Mo content of MC decreased from 28% to 17% and MTF generation was decreased in both stimulated and unstimulated cultures. However, this decreased MTF could not be explained by reduction in Mo number. In reconstitution experiments, T30 lymphoctes (Ly) did not suppress TO MTF generation and TO Ly did not restore T30 MTF generation, suggesting that the decreased MTF generation is not mediated by increased Ly suppressor activity. Neither heparin, warfarin nor hydrocortisone had any effect on Mo count or on MTF generation. These experiments suggest that small amounts of LPS activate a subpopulation of Mo, which is quickly lost from the circulation, while the remaining Mo are resistant to further LPS stimulation. Direct activation of this subpopulation of competent Mo by LPS may contribute to activation of blood coagulation in sepsis.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shweta Sinha ◽  
Ajay Prakash ◽  
Bikash Medhi ◽  
Alka Sehgal ◽  
Daniela I. Batovska ◽  
...  

Abstract Objective Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. Results In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL (intraperitoneal route), 69.89 ± 5.49 µg/mL (oral route), and 3.74 ± 1.64 µg/mL (oral route). The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.


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