Large Animal Models of Heart Failure

Silva, Kleiton Augusto Santos; Emter, Craig A.

doi:10.1016/j.jacbts.2020.04.011

Cited by 34 publications

(20 citation statements)

References 160 publications

(180 reference statements)

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“…Large animal models play a critical and expansive role in translating preclinical trials and approving new cardiovascular therapies. Some remarkably striking features such as greater anatomical-physiological similarity make them an absolute necessity in translational cardiovascular research (Silva & Emter, 2020).…”

Section: Introductionmentioning

confidence: 99%

Morphological importance of coronary ostia in sheep and swine

Pereira

Prates

Seyfert

et al. 2022

Anat Histol Embryol

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The aortic valve was investigated in 58 sheep and 60 swine without heart disease.After fixation in 4% formalin, the distance between the ostia and the elements of the right/left aortic sinuses was measured. For the left coronary ostium (LCO), it was found that in sheep 81% were below and 19% at the level of intercomissural line (IL). In pigs, 88.3% were below and 11.7% at the IL level. In sheep, the OCL was close to the right valve commissure (CVR) in 98.3% and close to the left valve commissure (CVV) in 1.7%. In pigs, it was close to RVC at 83.3% and close to LVC at 16.7%. Regarding to RCO, it was found that in sheep 69% was below, 1.7% was above and 29.3% at the IL level. In pigs, 20% were below, 15% above and 65% at the IL level. The distance of the RCO in relation to the valve commissures was 56.9% close to LVC and 43.1% close to RVC in sheep. In pigs, 81.7% were close to LVC and 18.3% close to RVC. The position of LCO was balanced between sheep and swine, while the RCO in swine was closer to CVE when compared with sheep. The accessory coronary ostium was observed in 18.6% of sheep and 10% of pigs. Thus, it is concluded that in sheep and swine the left coronary artery is perfused only in ventricular diastole. Perfusion of the right coronary artery occurs more frequently in diastole and less frequently in ventricular systole.

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Section: Introductionmentioning

confidence: 99%

Morphological importance of coronary ostia in sheep and swine

Pereira

Prates

Seyfert

et al. 2022

Anat Histol Embryol

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“…Pigs share a vast number of physiological and anatomical similarities with humans. More importantly, humans and pigs express the same major ion channels in cardiac myocytes, resulting in similar action potential length and morphology, in both the atria and ventricles [ 27 , 39 , 42 ], making the pig an ideal model for the study of electrophysiology [ 27 ]. We investigated a porcine ischemic heart failure model, since one of the main triggers leading to AF is acute myocardial infarction (AMI) [ 26 , 43 ] with up to 25% of patients developing AF during or after AMI [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Sex on the Susceptibility for Atrial Fibrillation in Pigs with Ischemic Heart Failure

Pauly

Vlcek

Zhang

et al. 2023

Cells

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Atrial fibrillation (AF) is the most prevalent arrhythmia, often caused by myocardial ischemia/infarction (MI). Men have a 1.5× higher prevalence of AF, whereas women show a higher risk for new onset AF after MI. However, the underlying mechanisms of how sex affects AF pathophysiology are largely unknown. In 72 pigs with/without ischemic heart failure (IHF) we investigated the impact of sex on ischemia-induced proarrhythmic atrial remodeling and the susceptibility for AF. Electrocardiogram (ECG) and electrophysiological studies were conducted to assess electrical remodeling; histological analyses were performed to assess atrial fibrosis in male and female pigs. IHF pigs of both sexes showed a significantly increased vulnerability for AF, but in male pigs more and longer episodes were observed. Unchanged conduction properties but enhanced left atrial fibrosis indicated structural rather than electrical remodeling underlying AF susceptibility. Sex differences were only observed in controls with female pigs showing an increased intrinsic heart rate, a prolonged QRS interval and a prolonged sinus node recovery time. In sum, susceptibility for AF is significantly increased both in male and female pigs with ischemic heart failure. Differences between males and females are moderate, including more and longer AF episodes in male pigs and sinus node dysfunction in female pigs.

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“…However, variations in the duration of occlusion, site of occlusion, and duration of reperfusion, among other parameters, are known to influence the infarct site, size, and ultimately the experimental outcome. For instance, occlusion of the LAD is used frequently to induce MI [ 88 , 89 ]. However, since this method is known to cause ventricular fibrillations and therefore higher mortality rates in pigs, many studies have alternatively occluded the left circumflex artery (LCx) to improve the survival of pigs post-MI.…”

Section: The Pig As a Translational MI Modelmentioning

confidence: 99%

Preclinical Large Animal Porcine Models for Cardiac Regeneration and Its Clinical Translation: Role of hiPSC-Derived Cardiomyocytes

Sridharan

Pracha

Rana

et al. 2023

Cells

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Myocardial Infarction (MI) occurs due to a blockage in the coronary artery resulting in ischemia and necrosis of cardiomyocytes in the left ventricular heart muscle. The dying cardiac tissue is replaced with fibrous scar tissue, causing a decrease in myocardial contractility and thus affecting the functional capacity of the myocardium. Treatments, such as stent placements, cardiac bypasses, or transplants are beneficial but with many limitations, and may decrease the overall life expectancy due to related complications. In recent years, with the advent of human induced pluripotent stem cells (hiPSCs), newer avenues using cell-based approaches for the treatment of MI have emerged as a potential for cardiac regeneration. While hiPSCs and their derived differentiated cells are promising candidates, their translatability for clinical applications has been hindered due to poor preclinical reproducibility. Various preclinical animal models for MI, ranging from mice to non-human primates, have been adopted in cardiovascular research to mimic MI in humans. Therefore, a comprehensive literature review was essential to elucidate the factors affecting the reproducibility and translatability of large animal models. In this review article, we have discussed different animal models available for studying stem-cell transplantation in cardiovascular applications, mainly focusing on the highly translatable porcine MI model.

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Large Animal Models of Heart Failure

Cited by 34 publications

References 160 publications

Morphological importance of coronary ostia in sheep and swine

Morphological importance of coronary ostia in sheep and swine

Effects of Sex on the Susceptibility for Atrial Fibrillation in Pigs with Ischemic Heart Failure

Preclinical Large Animal Porcine Models for Cardiac Regeneration and Its Clinical Translation: Role of hiPSC-Derived Cardiomyocytes

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