scholarly journals CineCT imaging platform for in-vivo and ex-vivo measurement of myocardial biomechanics post myocardial infarction and following intramyocardial delivery of theranostic hydrogel

2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
D Midgett ◽  
RA Ricardo Avendano ◽  
IM Inga Melvinsdottir ◽  
SU Selen Uman ◽  
SLT Stephanie Thorn ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Myocardial Strain ◽  
Perfused Heart ◽  
Active Deformation ◽  
Intramyocardial Injection ◽  
Passive Deformation ◽  
Intramyocardial Delivery ◽  
Yorkshire Pigs

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH) Purpose Myocardial infarction (MI) induces acute regional changes in myocardial strain and stiffness in the infarct and the remote areas of the left ventricle (LV), which lead to adverse changes in LV geometry and function. We hypothesize that cineCT imaging could evaluate these biomechanical changes along with the effects of intramyocardial delivery of theranostic hydrogels.  Introduction We present an experimental platform to assess changes in the deformation of the LV myocardium using contrast cineCT (CCT) imaging of the beating porcine heart (active deformation) before and after acute MI and intramyocardial delivery of an imageable theranostic hydrogel. We then assess the acute effects of hydrogel delivery early post-MI on biomechanics (passive deformation) using an ex vivo perfused heart preparation.  Methods Contrast cineCT imaging was performed using 64-slice CT on 5 Yorkshire pigs without MI (n = 3) or with MI (n = 2). MI pigs had serial imaging performed before and 1 hour after acute surgical coronary occlusion to induce anterolateral MI. One MI pig was also imaged 1 hour after intramyocardial injection of a novel imageable theranostic iodinated hydrogel within the MI region. Post euthanasia, excised hearts were flushed with chilled UW cardioplegic solution and mounted on a custom inflation apparatus for cineCT imaging during LV inflation by external pump. LV pressure was cycled between 10 and 60 mmHg at 35 bpm. Dilute iohexol was injected into aortic root and UW perfusate (15 ml, 1 ml/sec). CineCT image series were reconstructed, contrast enhanced, resampled to the LV long axis (Z), and exported as a series of 10 CT volumes covering 0-90% of the cardiac/inflation cycle. Volumes were registered incrementally using nonlinear image registration (BioImageSuite) and the calculated displacement at each time point was exported at a resolution of 1 mm. A custom Matlab program was used to fit the displacement field to local trilinear polynomials and then calculate the displacement gradients and 3D Lagrangian strains. To estimate the accuracy of this approach, cardiac volumes were also numerically deformed using a 10 pixel translation and 5% triaxial stretch. Results We successfully acquired serial in-vivo and ex-vivo 3D CineCT images for assessment of the active and passive LV myocardial deformation and tracked deformation through the full cardiac/inflation cycle (Figure 2). Numerical deformation tests showed average tracking errors of < 0.2 mm (1/4 pixel) in the X,Y,Z directions of the volume. These resulted in Lagrangian strain errors of < 0.47% for the in-plane strains EXX and EYY (radial and circumferential plane) and < 0.5% for EZZ (long axis).  Conclusions We have developed a novel CineCT imaging platform that allows for high resolution in-vivo and ex-vivo measurement of myocardial biomechanics post-MI and following intramyocardial delivery of imageable theranostic hydrogels, which may improve early active and passive biomechanics.

scholarly journals Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zeping Qiu ◽  
Jingwen Zhao ◽  
Fanyi Huang ◽  
Luhan Bao ◽  
Yanjia Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Fibrosis ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Cost Effective ◽  
Intramyocardial Injection ◽  
Undesirable Consequence ◽  
Adverse Remodeling

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

scholarly journals Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 899
Author(s):  
Clara Liu Chung Ming ◽  
Kimberly Sesperez ◽  
Eitan Ben-Sefer ◽  
David Arpon ◽  
Kristine McGrath ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ex Vivo ◽  
Myocardial Damage ◽  
Cardiovascular Disorder ◽  
Model Systems ◽  
Ex Vivo Model ◽  
Disease Manifestation

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

scholarly journals Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

2021 ◽  
Author(s):  
Clara Liu Chung Ming ◽  
Kimberly Sesperez ◽  
Eitan Ben-Sefer ◽  
David Arpon ◽  
Kristine McGrath ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ex Vivo ◽  
Myocardial Damage ◽  
Cardiovascular Disorder ◽  
Model Systems ◽  
Ex Vivo Model ◽  
Disease Manifestation

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

Ex vivo-expanded bone marrow CD34+ for acute myocardial infarction treatment: in vitro and in vivo studies

Cytotherapy ◽  
2011 ◽  
Vol 13 (9) ◽  
pp. 1140-1152 ◽  
Author(s):  
Monica Gunetti ◽  
Alessio Noghero ◽  
Fabiola Molla ◽  
Lidia Irene Staszewsky ◽  
Noeleen de Angelis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Bone Marrow ◽  
Ex Vivo ◽  
In Vivo Studies

scholarly journals Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

2018 ◽  
Vol 114 (8) ◽  
pp. 1178-1188 ◽  
Author(s):  
Daniel S Gaul ◽  
Julien Weber ◽  
Lambertus J van Tits ◽  
Susanna Sluka ◽  
Lisa Pasterk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Bone Marrow ◽  
Arterial Thrombosis ◽  
Ex Vivo ◽  
Neutrophil Extracellular Traps ◽  
Wild Type ◽  
Rotational Thromboelastometry ◽  
Extracellular Traps

AbstractAimsSirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI).Methods and resultsUsing a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3−/− mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P < 0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry revealed accelerated clot formation and increased clot stability in Sirt3−/− compared to wild-type blood. rotational thromboelastometry of cell-depleted plasma showed accelerated clotting initiation in Sirt3−/− mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap formation was increased in Sirt3−/− bone marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3−/− mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in bone marrow -derived Sirt3−/− neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, P < 0.01).ConclusionsSirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of neutrophil extracellular traps and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+-boosters may provide a novel therapeutic target to prevent or treat thrombotic arterial occlusion in myocardial infarction or stroke.

scholarly journals Effects of Sodium Nitroprusside on Platelet Adhesion, Subsequent Aggregation and Vasoconstriction

1977 ◽  
Author(s):  
H.R. Baumgartner
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Sodium Nitroprusside ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Balloon Catheter ◽  
Strong Inhibitor ◽  
Induced Aggregation

Sodium nitroprusside (SNP), a potent vasodilator, has shown beneficial effects in acute myocardial infarction. Since platelets may play an important role in the pathogenesis of myocardial infarction, the effect of SNP on their interaction with rabbit aorta subendothelium was investigated in vivo and under controlled blood flow conditions ex vivo and in vitro.One iliac artery and the abdominal aorta were denuded of endothelium by balloon catheter injury during infusion of glucose, SNP at 6 or 12 μg/kg/min in groups of 12, 6 and 7 rabbits respectively. The aorta and their branches were perfuse-fixed under controlled pressure 10 min after denudation. Morphometric evaluation showed dose-dependent and significant (2p < 0.01 or 0.001) inhibition of platelet spreading, adhesion and aggregation. The latter was abolished at the higher dose of SNP. Denudation and subsequent platelet adhesion caused strong vasoconstriction (2p < 0.001) which was inhibited by SNP (2p < 0.01).By exposure of subendothelium to either citrated blood or native blood in a flow chamber (2000 sec-1 shear rate) strong inhibition of spreading and adhesion-induced aggregation was again demonstrated at 6 and 12 μg/kg/min SNP. In vitro, adhesion-induced aggregation was completely abolished after the addition of SNP to rabbit (at 20 μg/ml) or human blood (2 μg/ml). 1 μg/ml PGE1 was needed to induce a similar inhibitory effect.Thus SNP is a strong inhibitor of platelet function and of injury + platelet induced vasoconstriction. These findings may explain its beneficial effect in acute myocardial infarction.

scholarly journals Lower retention after retrograde coronary venous infusion compared with intracoronary infusion of mesenchymal stromal cells in the infarcted porcine myocardium

2019 ◽  
Vol 3 (1) ◽  
pp. e000006 ◽  
Author(s):  
Wouter A Gathier ◽  
Mira van der Naald ◽  
Bas R van Klarenbosch ◽  
Anton E Tuinenburg ◽  
John LM Bemelmans ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Pericardial Fluid ◽  
Cardiac Cell ◽  
Cell Retention ◽  
Intramyocardial Injection ◽  
Advantages And Disadvantages ◽  
Venous Infusion

BackgroundCommonly used strategies for cell delivery to the heart are intramyocardial injection and intracoronary (IC) infusion, both having their advantages and disadvantages. Therefore, alternative strategies, such as retrograde coronary venous infusion (RCVI), are explored. The aim of this confirmatory study was to compare cardiac cell retention between RCVI and IC infusion. As a secondary end point, the procedural safety of RCVI is assessed.MethodsFour weeks after myocardial infarction, 12 pigs were randomised to receive mesenchymal stromal cells, labelled with Indium-111, via RCVI (n=6) or IC infusion (n=6). Four hours after cell administration, nuclear imaging was performed to determine the number of cells retained in the heart both in vivo and ex vivo. Procedure-related safety measures were reported.ResultsCardiac cell retention is significantly lower after RCVI compared with IC infusion (in vivo: RCVI: median 2.89% vs IC: median 13.74%, p=0.002, ex vivo: RCVI: median 2.55% vs IC: median 39.40%, p=0.002). RCVI led to development of pericardial fluid and haematomas on the frontal wall of the heart in three cases. Coronary venous dissection after RCVI was seen in three pigs, of which one also developed pericardial fluid and a haematoma. IC infusion led to no flow in one pig.ConclusionRCVI is significantly less efficient in delivering cells to the heart compared with IC infusion. RCVI led to more procedure-related safety issues than IC infusion, with multiple cases of venous dissection and development of haematomas and pericardial fluid collections.

scholarly journals Pharmacological Justification for the Medicinal Use of Plumeria rubra Linn. in Cardiovascular Disorders

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 251
Author(s):  
Imran Ahmad Khan ◽  
Musaddique Hussain ◽  
Shahzada Khurram Syed ◽  
Malik Saadullah ◽  
Ali M. Alqahtani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Antioxidant Properties ◽  
Rabbit Aorta ◽  
Cardiovascular Disorders ◽  
Aorta Ring ◽  
Crude Leaf Extract ◽  
Underlying Mechanisms ◽  
Plumeria Rubra

Plumeria rubra (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of P. rubra in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of P. rubra were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, P. rubra displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. P. rubra has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.

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