In Vivo Thromboscintigraphy With Indium-111-Labeled Platelets In A Dog-Catheter Model

1981 ◽  
Author(s):  
D C Price ◽  
M J Lipton ◽  
J A Hartmeyer ◽  
R J Prager

Autologous platelets from mongrel dogs have been labeled with 200-400 μCi Indium-111 complexed to oxine using the technique of Thakur, McAfee and others. Intraarterial thrombogenesis was studied in vivo by advancing a polyethylene angiographic catheter from a femoral into a carotid artery, then serially imaging the catheter over periods of 0.5-3 hours by scintillation camera with interfaced computer. Quantitative uptake was derived from computer processing of the studies, and compared with in vitro In-111 counts and clot weight obtained at various times by catheter excision. Labeled platelets were injected prior to or at periods of 2 or 24 hours after catheter insertion in order to evaluate both forming and preformed thrombus. Platelet In-111 radioactivity was found to peak at 30-80 minutes in newly forming thrombus and to fall thereafter. In vitro In-111 activity correlated well with wet clot weight.In-111 (% inj. dose) = 0.00209 × (mgm clot) + 0.00091 (r = 0.882) (n = 24)In vivo correlation was also linear, but with a broader scatter of data points. At the peak, In-111 uptake was 0.06044). 019% of i.d. per cm of catheter by in vitro measurement, and clot weight was 27.9±5.6 mgm per cm. Preformed thrombus picked up substantially less of the label (2 hr: 0.017±0.011% i.d./cm; 24 hr: 0.00245).001% i.d./cm) (n=6) and was not imageable in vivo. The study documents the effectiveness of this new platelet radiolabel for quantitative in vivo scintigraphy of newly forming thrombus, which can be useful for comparison of different anti-thrombogenic regimens and different biomaterials. It also indicates, however, the problems that can be anticipated in attempting to image established thrombus in vivo.

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. e66-e73 ◽  
Author(s):  
Chih-Wen Ni ◽  
Haiwei Qiu ◽  
Amir Rezvan ◽  
Kihwan Kwon ◽  
Douglas Nam ◽  
...  

Abstract Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.


Author(s):  
M D Ezekowitz ◽  
E O Smith ◽  
A C Cox ◽  
S W Herren ◽  
F B Taylor

Indium-III is 2.8 day half-life gamma emitting radionuclide which is suitable for scintigraphic study and has been used to label platelets without causing significant attenuation of function. The purpose of this study was to utilize this technique for localization of left ventricular mural thrombi in patients with regional LV dysfunction. The patient population consisted of 55 patients between the ages of 24 and 77 (53.4 ± 11.3, mean ± 1SD). Twenty-four required coronary artery bypass surgery with aneurysmectomy for intractable angina and/or heart failure. This provided an opportunity to validate the preoperative findings at surgery. Platelets were separated from 43 ml blood in ACD solution by centrifugation and were labelled in ACD:saline (1:7) solution at a pH of 6.5-7.0. A total of 3.8 ± 2.9 × 109 (mean ± 1SD) platelets labelled with 451.9 ± 111.6 μCi with a final labelling efficiency of 72.1±14.1% were injected IV. Platelet recovery at 15 minutes was 51.1 ± 17.7% (mean ± 1SD). EM studies before and after labelling showed no morphological change due to the labelling procedure. Aggregation of platelets in response to ADP and collagen was not altered significantly during the labelling process. Patients on aspirin showed the expected inhibitory effect of aspirin on collagen and ADP induced aggregation. Patients were imaged in multiple views on at least alternate days for a maximum of 8 days. Seventeen had positive studies. In those patients in which surgical confirmation of the scintigraphic studies was possible, a sensitivity of 72% and specificity of 100% was found. We conclude that: 1) Indium-111 platelet scintigraphy promises to be a reliable method of identifying intracardiac thrombi. 2) It may also be useful in monitoring thrombus activity in vivo. 3) Patients on aspirin incorporated platelets onto the thrombus surface in spite of showing the expected inhibitory response to ADP and collagen induced aggregation in vitro.


2020 ◽  
Vol 115 ◽  
pp. 111093
Author(s):  
Xiao Yu ◽  
Dongyang Li ◽  
Yuanchao Liu ◽  
Pengfei Ding ◽  
Xianghui He ◽  
...  

2016 ◽  
Vol 120 (10) ◽  
pp. 1141-1150 ◽  
Author(s):  
Steven G. Denniss ◽  
Rebecca J. Ford ◽  
Christopher S. Smith ◽  
Andrew J. Jeffery ◽  
James W. E. Rush

Exaggerated cyclooxygenase (COX) and thromboxane-prostanoid (TP) receptor-mediated endothelium-dependent contraction can contribute to endothelial dysfunction. This study examined the effect of resveratrol (RSV) on endothelium-dependent contraction and cell signaling in the common carotid artery (CCA) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)-stimulated endothelium-dependent nitric oxide synthase (NOS)-mediated relaxation in precontracted SHR CCA was impaired (maximum 73 ± 6% vs. 87 ± 5% in WKY) ( P < 0.05) by competitive COX-mediated contraction. Chronic (28-day) treatment in vivo (drinking water) with a ∼0.075 mg·kg−1·day−1 RSV dose affected neither endothelium-dependent relaxation nor endothelium-dependent contraction and associated prostaglandin (PG) production evaluated in non-precontracted NOS-blocked CCA. In contrast, a chronic ∼7.5 mg·kg−1·day−1 RSV dose improved endothelium-dependent relaxation (94 ± 6%) and attenuated endothelium-dependent contraction (58 ± 4% vs. 73 ± 5% in No-RSV) and PG production (183 ± 43 vs. 519 ± 93 pg/ml) in SHR CCA, while U46619-stimulated TP receptor-mediated contraction was unaffected. In separate acute in vitro experiments, 20-μM RSV preincubation attenuated endothelium-dependent contraction (6 ± 4% vs. 62 ± 2% in No Drug) and PG production (121 ± 15 vs. 491 ± 93 pg/ml) and attenuated U46619-stimulated contraction (134 ± 5% vs. 171 ± 4%) in non-precontracted NOS-blocked SHR CCA. Compound C, a known AMP-activated protein kinase (AMPK) inhibitor, did not prevent the RSV attenuating effect on Ach- and U46619 -stimulated contraction but did prevent the RSV attenuating effect on PG production (414 ± 58 pg/ml). These data demonstrate that RSV can attenuate endothelium-dependent contraction both by suppressing arterial wall PG production, which may be partially mediated by AMPK, and by TP receptor hyporesponsiveness, which does not appear to be mediated by AMPK.


2010 ◽  
Vol 13 (6) ◽  
pp. 1204-1214 ◽  
Author(s):  
Franz Josef Gildehaus ◽  
Florian Haasters ◽  
Inga Drosse ◽  
Erika Wagner ◽  
Christian Zach ◽  
...  

2014 ◽  
Vol 41 (9) ◽  
pp. 1710-1719 ◽  
Author(s):  
Andor W. J. M. Glaudemans ◽  
Elena Bonanno ◽  
Filippo Galli ◽  
Clark J. Zeebregts ◽  
Erik F. J. de Vries ◽  
...  

Microsurgery ◽  
1998 ◽  
Vol 18 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Giulio Gherardini ◽  
Ali Gürlek ◽  
Douglas Cromeens ◽  
Ghislaine A. Joly ◽  
Bao-Guang Wang ◽  
...  

2004 ◽  
Vol 19 (1) ◽  
pp. 93-98 ◽  
Author(s):  
L. Aloj ◽  
M. Panico ◽  
C. Caraco ◽  
S. Del Vecchio ◽  
C. Arra ◽  
...  

2010 ◽  
Vol 109 (2) ◽  
pp. 305-313 ◽  
Author(s):  
Nisreen Mansour Omar ◽  
Janice M. Marshall

We investigated how the ability of adenosine to release nitric oxide (NO) from carotid artery in vitro, and dilator responses evoked in carotid circulation in vivo by systemic infusion of adenosine, change with age in rats of 4–5, 10–12, and 42–44 wk (juvenile, mature, and middle aged). A secondary aim was to follow age-related changes in carotid/cerebral autoregulation. In opened carotid artery, graded doses of adenosine evoked graded increases in NO output measured with a NO sensor that were greater in mature and middle-aged than juvenile rats. Infusion of adenosine to reduce mean arterial pressure (ABP) to ∼60 mmHg increased carotid vascular conductance (CVC) in all groups, but the increase was larger in mature rats; carotid blood flow (CBF) was unchanged in juvenile, increased in mature, but fell in 4/8 middle-aged rats. The NO synthase inhibitor nitro l-arginine methyl ester (l-NAME; 10 mg/kg iv) increased baseline ABP in all groups but caused larger percentage reductions in baseline CVC and CBF in mature and middle-aged than juvenile rats. Thereafter, the adenosine-evoked increase in CVC was unchanged in juvenile and middle-aged rats, yet CBF remained constant in juvenile but increased in middle-aged rats. In mature rats, the evoked increases in CVC and CBF were attenuated and further attenuated by l-NAME at 30 mg/kg. We propose that the ability of adenosine to release NO and cause vasodilation in the carotid artery and its circulation is greater in mature, than juvenile or middle-aged rats, but NO has greater tonic dilator influence in carotid circulation of mature and middle-aged than juvenile rats. By middle age, the lower limit of cerebral autoregulation has increased such that the tonic dilator influence of NO on ABP and CVC limits autoregulation of CBF to depressor responses. However, partial NO synthase inhibition overcomes this impairment, raising baseline ABP and allowing adenosine-evoked increases in CVC to increase CBF.


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