Embozene™ microspheres induced nonreperfused myocardial infarction in an experimental swine model

Varga-Szemes, Ákos; Kiss, Pál; Brott, Brigitta C.; Wang, Dezhi; Símor, Tamás; Elgavish, Gabriel A.

doi:10.1002/ccd.24418

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…Generally, chronic infarctions in large animal models are obtained by surgical ligation of a coronary artery via a thoracotomy [ 19 , 21 – 23 ], the use of the ameroid constrictor, or occlusion, either temporary using an angioplasty balloon catheter [ 6 – 9 , 15 , 17 , 20 , 24 – 29 ] or permanent with different embolization systems, including the endovascular deployment of a “flow reductor” inside the target coronary artery [ 30 ], microbead embolization [ 31 , 32 ], embolization using gelfoam alone [ 4 , 33 ] or in combination with coils, [ 34 ] and deployment of an ivalon plug [ 35 ]. A closed chest minimally invasive model is more comparable to human MI pathology than open chest models [ 27 ], and it carries less risk of complications and infections [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a Closed Chest Model of Chronic Myocardial Infarction in Swine: Magnetic Resonance Imaging and Pathological Evaluation

et al. 2013

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Our aim was to develop an easy-to-induce, reproducible, and low mortality clinically relevant closed-chest model of chronic myocardial infarction in swine using intracoronary ethanol and characterize its evolution using MRI and pathology. We injected 3-4 mL of 100% ethanol into the mid-LAD of anesthetized swine. Heart function and infarct size were assessed serially using MRI. Pigs were euthanized on days 7, 30, and 90 (n = 5 at each timepoint). Postoperative MRI revealed compromised contractility and decreased ejection fraction, from 53.8% ± 6.32% to 43.79% ± 7.72% (P = 0.001). These values remained lower than baseline thorough the followup (46.54% ± 11.12%, 44.48% ± 7.77%, and 40.48% ± 6.40%, resp., P < 0.05). Progressive remodeling was seen in all animals. Infarcted myocardium decreased on the first 30 days (from 18.09% ± 7.26% to 9.9% ± 5.68%) and then stabilized (10.2% ± 4.21%). Pathology revealed increasing collagen content and fibrous organization over time, with a rim of preserved endocardial cells. In conclusion, intracoronary ethanol administration in swine consistently results in infarction. The sustained compromise in heart function and myocardial thinning over time indicate that the model may be useful for the preclinical evaluation of and training in therapeutic approaches to heart failure.

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Section: Discussionmentioning

confidence: 99%

Development of a Closed Chest Model of Chronic Myocardial Infarction in Swine: Magnetic Resonance Imaging and Pathological Evaluation

et al. 2013

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“…Farm swine (n ¼ 3, 30 kg) received humane care in compliance with the UCSF IACUC. This animal model has similar vascular anatomy and physiology to humans, and has been used extensively in prior IAC simulations [26,27]. Interventional procedures included anesthesia (Isoflurane), X-ray fluoroscopy, percutaneous transarterial catheterization of the hepatic artery, and percutaneous transvenous catheterization of the vena cava.…”

Section: Methods Of Approachmentioning

confidence: 99%

Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical Study

Patel

Saeed

Yee

et al. 2014

Journal of Medical Devices

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Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical StudyTo develop a novel endovascular chemotherapy filter (CF) able to remove excess drug from the blood during intra-arterial chemotherapy delivery (IAC), thus preventing systemic toxicities and thereby enabling higher dose IAC. A flow circuit containing 2.5 mL of ion-exchange resin was constructed. Phosphate-buffered saline (PBS) containing 50 mg doxorubicin (Dox) was placed in the flow model with the hypothesis that doxorubicin would bind rapidly to resin. To simulate IAC, 50 mg of doxorubicin was infused over 10 min into the flow model containing resin. Similar testing was repeated with porcine serum. Doxorubicin concentrations were measured over 60 min and compared to controls (without resin). Single-pass experiments were also performed. Based on these experiments, an 18F CF was constructed with resin in its tip. In a pilot porcine study, the device was deployed under fluoroscopy. A control hepatic doxorubicin IAC model (no CF placed) was developed in another animal. A second CF device was created with a resin membrane and tested in the infrarenal inferior vena cava (IVC) of a swine. In the PBS model, resin bound 76% of doxorubicin in 10 min, and 92% in 30 min (P < 0.001). During IAC simulation, 64% of doxorubicin bound in 10 min and 96% in 60 min (P < 0.001). On average, 51% of doxorubicin concentration was reduced during each pass in single pass studies. In porcine serum, 52% of doxorubicin bound in 10 min, and 80% in 30 min (P < 0.05). CF device placement and administration of IAC were successful in three animals. No clot was present on the resin within the CF following the in vivo study. The infrarenal IVC swine study demonstrated promising results with up to 85% reduction in peak concentration by the CF device. An endovascular CF device was developed and shown feasible in vitro. An in vivo model was established with promising results supporting high-capacity rapid doxorubicin filtration from the blood that can be further evaluated in future studies.

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“…One and a half month‐old growing farm pigs (30–32 kg, Pork Power Co., Turlock, CA) received humane care in compliance with the IACUC. This animal model has similar LV anatomy and physiology to humans . A fixed landmark on the left anterior descending (LAD) coronary artery (distal to 2nd diagonal) was used for positioning the angioplasty balloon catheter, LAD occlusion and microemboli delivery to create a reproducible area at risk and minimize fatal fibrillation .…”

Section: Methodsmentioning

confidence: 99%

MRI demonstrates a decrease in myocardial infarct healing and increase in compensatory ventricular hypertrophy following mechanical microvascular obstruction

Bajwa

Suhail

et al. 2014

Magnetic Resonance Imaging

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Embozene™ microspheres induced nonreperfused myocardial infarction in an experimental swine model

Abstract: The generation of nonreperfused MI is feasible by percutaneous injection of Embozene into the coronary artery system. The MI model thus obtained is suitable for the purposes of MRI experiments.

Cited by 11 publications

References 18 publications

Development of a Closed Chest Model of Chronic Myocardial Infarction in Swine: Magnetic Resonance Imaging and Pathological Evaluation

Development of a Closed Chest Model of Chronic Myocardial Infarction in Swine: Magnetic Resonance Imaging and Pathological Evaluation

Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical Study

MRI demonstrates a decrease in myocardial infarct healing and increase in compensatory ventricular hypertrophy following mechanical microvascular obstruction

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