Development of an Ovine Model of Myocardial Infarction

Rabbani, Shahram; Ahmadi, Hossein; Fayazzadeh, Ehsan; Sahebjam, Mohammad; Boroumand, Mohammad Ali; Sotudeh, Masoud; Nassiri, Seyed Mahdi

doi:10.1111/j.1445-2197.2007.04359.x

Cited by 12 publications

(15 citation statements)

References 11 publications

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“…Previous ovine models of postinfraction heart failure through the ligation of either the distal LAD or the diagonal branches off of the LAD have shown reproducible results. This has been attributed to the consistent territory of myocardium supplied by this artery as well as the lack of collateral vascularity [16–18]. …”

Section: Discussionmentioning

confidence: 99%

A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets

Spata

Bobek

Whitson

et al. 2013

BioMed Research International

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Objective. There is a paucity of a biological large animal model of myocardial infarction (MI). We hypothesized that, using autologous-aggregated platelets, we could create an ovine model that was reproducible and more closely mimicked the pathophysiology of MI. Methods. Mepacrine stained autologous platelets from male sheep (n = 7) were used to create a myocardial infarction via catheter injection into the mid-left anterior descending (LAD) coronary artery. Serial daily serum troponin measurements were taken and tissue harvested on post-embolization day three. Immunofluorescence microscopy was used to detect the mepacrine-stained platelet-induced thrombus, and histology performed to identify three distinct myocardial (infarct, peri-ischemic “border zone,” and remote) zones. Results. Serial serum troponin levels (μg/mL) measured 0.0 ± 0.0 at baseline and peaked at 297.4 ± 58.0 on post-embolization day 1, followed by 153.0 ± 38.8 on day 2 and 76.7 ± 19.8 on day 3. Staining confirmed distinct myocardial regions of inflammation and fibrosis as well as mepacrine-stained platelets as the cause of intravascular thrombosis. Conclusion. We report a reproducible, unique model of a biological myocardial infarction in a large animal model. This technique can be used to study acute, regional myocardial changes following a thrombotic injury.

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Section: Discussionmentioning

confidence: 99%

A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets

Spata

Bobek

Whitson

et al. 2013

BioMed Research International

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“…For this reason, a reproducible model of myocardial infarction in large animals is an essential step not only in the development of new therapies but also improved understanding of cell and molecular pathology following cardiac ischemia (5). Both in experimental animal models and patients, lethal arrhythmia is the leading cause of death following MI, accounting for 12.5–29.4% and 30–40% of mortality in large animal models and humans, respectively (6,7,8,9). In an effort to more closely approximate clinical scenarios and to decrease mortality of experimental animals, actively preventing arrhythmias following infarction is critical in large animal studies.…”

Section: Discussionmentioning

confidence: 99%

“…Large animal models of myocardial infarction have been used in experimental cardiology for many decades as they accurately model this devastating human disease. However the experimental MI procedure is associated with high mortality due to arrhythmias, ranging from 16% to 29% in ovine models (6,7,8), and even higher incidence in swine models. The incidence of ventricular fibrillation in pigs is 19% within the first 10 minutes after the occlusion of a coronary artery, increasing to 38% in 20 to 40 minutes after ischemia, with a mortality of 12.5% due to ventricular fibrillation (9).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic amiodarone and lidocaine improve survival in an ovine model of large size myocardial infarction

Li¹,

Wei²,

Watkins³

et al. 2013

Journal of Surgical Research

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Background Large animal models serve as a critical link in the translation of basic science to clinical practice. However, large animal models of MI, especially a large size MI, are associated with high mortality due to arrhythmia. The prophylactic effect of amiodarone and lidocaine were retrospectively reviewed in our ovine MI model. Methods One hundred-fourteen Dorset hybrid sheep with 25–30% MI were included in this study. Animals were prophylacticly treated with amiodarone plus lidocaine before ligation of the 4–6 coronary artery branches supplying the apex of the heart (arrhythmia-prevention group, AP group, n=45) and with epinephrine (shock-prevention group, SP group, n=49), respectively. Animals without prophylactic treatment (no-prevention group, NP group, n=20) were used as the control group. The incidence of arrhythmia requiring treatment, mortality due to arrhythmias, hemodynamics and arterial blood gas values during the surgery were analyzed in these three groups. Results There was no significant difference in infarct size among the three groups. The incidence of arrhythmia requiring treatment was significantly decreased in the AP group compared to the NP or SP groups 4.4% (AP) vs. 35% (SP) or 45% (NP) p<0.05). The mortality due to lethal arrhythmia was 2.2% in the AP group, significantly lower than in the NP group (15%) or the SP group (18.4%). Besides heart rate (HR), hemodynamic data there were no significant differences between the AP and NP group. Metabolic acidosis was not observed in any group as indicated by pH and lactate values. Conclusions Prophylactic amiodarone plus lidocaine decreased the mortality due to lethal arrhythmia after acute myocardial infarction in our sheep model without significant negative effect on hemodynamics. However, epinephrine improved hemodynamics but also increased mortality due to lethal arrhythmia. Thus, prophylactic amiodarone plus lidocaine is recommended to improve the stability in a large MI animal model.

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“…Surgical procedures were performed under general anaesthesia and electrocardiographic monitoring (Rabbani et al ., ; Kim et al ., ). The sheep were anaesthetized by intravenous injection of sodium pentobarbital (30 mg/kg).…”

Section: Methodsmentioning

confidence: 96%

“…The sheep were anaesthetized by intravenous injection of sodium pentobarbital (30 mg/kg). Acute MI was inducted by ligating the second diagonal branch of the left anterior descending coronary artery, as described previously (Rabbani et al ., ). Occlusion of the coronary artery was confirmed by the cyanotic appearance of the ischaemic area and ventricular hypokinesia, plus ST‐segment changes on electrocardiography (ECG).…”

Section: Methodsmentioning

confidence: 97%

Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction

Fathi

Nassiri

Atyabi

et al. 2012

J Tissue Eng Regen Med

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Hydrogels are currently used as interesting constructs for the delivery of proteins. In this study, a novel polyvinyl alcohol-dextran (PVA-Dex) blend hydrogel was used for controlled delivery of basic-fibroblast growth factor (bFGF). These biocompatible constructs were sutured to the epicardium as patches on the heart surface to provide slow release of bFGF to the infarcted site in an ovine model of myocardial infarction (MI). Eighteen sheep were randomly divided into three groups (n = 6 each), including group I (control without any patch and bFGF), group II (patch without bFGF) and group III (patch incorporating 100 µg bFGF). They were subjected to coronary artery ligation after lateral thoracotomy, and then in groups II and III the patches were implanted 20-30 min after MI. Cardiac function was assessed by both echocardiography and magnetic resonance imaging (MRI) 2 months after implantation. Then the animals were sacrificed and the hearts subjected to histopathological examination, immunohistochemistry and electron microscopy. Heart lysates were subject to protein expression analysis through western blotting. The results showed that sustained release of bFGF using PVA-Dex blend hydrogel strongly stimulated angiogenesis and increased wall thickness index in the infarcted myocardium. The patch also significantly attenuated the increase in left ventricular end-systolic diameter, but it did not improve cardiac function within 2 months of myocardial infarction. In conclusion, PVA-Dex gel incorporating bFGF can be used as a sustained release construct for therapeutic angiogenesis in ischaemic heart disease.

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Development of an Ovine Model of Myocardial Infarction

Abstract: In conclusion, we developed a practical and safe method for producing myocardial infarction in large animal models.

Cited by 12 publications

References 11 publications

A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets

A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets

Prophylactic amiodarone and lidocaine improve survival in an ovine model of large size myocardial infarction

Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction

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