A practical guide to setting up pig models for cardiovascular catheterization, electrophysiological assessment and heart disease research

Schüttler, Dominik; Tomsits, Philipp; Bleyer, Christina; Vlcek, Julia; Pauly, Valerie; Hesse, Nora; Sinner, Moritz F.; Merkus, Daphne; Hamers, Jules; Kääb, Stefan; Clauß, Sebastian

doi:10.1038/s41684-021-00909-6

Cited by 17 publications

(20 citation statements)

References 49 publications

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“…Furthermore, the porcine immune system is very similar to the human immune system, especially compared to mice ( Mair et al, 2014 ; Pabst, 2020 ). Clinical routine techniques and equipment used for humans can easily be applied to pigs, a large number of disease models have been established and well characterized ( Schuttler et al, 2022 ), and targeted genetic modification has become feasible with recent technological advances ( Park et al, 2015 ; Langin et al, 2018 ; Renner et al, 2020 ; Riedel et al, 2020 ; Stirm et al, 2021 ). Moreover, pigs present action potentials and electrophysiological properties similar to humans as they express the same major ion currents (except I to ) ( Kaese et al, 2013 ; Piktel and Wilson, 2019 ).…”

Section: Future Challenges: Studying Macrophages In Arrhythmogenesis ...mentioning

confidence: 99%

Cardiac Macrophages and Their Effects on Arrhythmogenesis

et al. 2022

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Cardiac electrophysiology is a complex system established by a plethora of inward and outward ion currents in cardiomyocytes generating and conducting electrical signals in the heart. However, not only cardiomyocytes but also other cell types can modulate the heart rhythm. Recently, cardiac macrophages were demonstrated as important players in both electrophysiology and arrhythmogenesis. Cardiac macrophages are a heterogeneous group of immune cells including resident macrophages derived from embryonic and fetal precursors and recruited macrophages derived from circulating monocytes from the bone marrow. Recent studies suggest antiarrhythmic as well as proarrhythmic effects of cardiac macrophages. The proposed mechanisms of how cardiac macrophages affect electrophysiology vary and include both direct and indirect interactions with other cardiac cells. In this review, we provide an overview of the different subsets of macrophages in the heart and their possible interactions with cardiomyocytes under both physiologic conditions and heart disease. Furthermore, we elucidate similarities and differences between human, murine and porcine cardiac macrophages, thus providing detailed information for researchers investigating cardiac macrophages in important animal species for electrophysiologic research. Finally, we discuss the pros and cons of mice and pigs to investigate the role of cardiac macrophages in arrhythmogenesis from a translational perspective.

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Section: Future Challenges: Studying Macrophages In Arrhythmogenesis ...mentioning

confidence: 99%

Cardiac Macrophages and Their Effects on Arrhythmogenesis

et al. 2022

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“…Inclusion in either the CTL or the IHF group was random. Ischemic heart failure was induced by occlusion of the left anterior descending artery (LAD) for 90 min as previously described [ 13 , 14 ]. After 30 days, IHF pigs underwent the same experimental procedures as age- and weight-matched controls.…”

Section: Methodsmentioning

confidence: 99%

“…Experimental procedures were recently described in detail [ 13 , 14 ]. In short, all pigs were given seven days of acclimatization in the facility to avoid any stress-induced alterations of experimental results.…”

Section: Methodsmentioning

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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“…Model induction was previously described in detail. 7,10 In brief, pigs were sedated (by intramuscular ketamine [20 mg/kg], azaperone [10 mg/kg] and atropine [.05 mg/kg]), anaesthetized (induced by intravenous midazolam [.5 mg/kg] and maintained by intravenous fentanyl [.05 mg/kg], propofol [.5 mg/kg/min]) and mechanically ventilated (initial parameters: peak pressure 18-25 mmHg, peep 5 mmHg, tidal volume 6-8 mL/ kg, FiO2 21%; further adjustments according to regular blood gas test results). The right external jugular vein and right carotid artery were surgically prepared, and sheaths were inserted (9F and 8F, respectively).…”

Section: Pig Modelmentioning

confidence: 99%

Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure

Zhang,

Vlcek,

Pauly

et al. 2023

Eur J Clin Investigation

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BackgroundAtrial fibrillation (AF) is the most common arrhythmia and is associated with considerable morbidity and mortality. Ischaemic heart failure (IHF) remains one of the most common causes of AF in clinical practice. However, ischaemia‐mediated mechanisms leading to AF are still incompletely understood, and thus, current treatment approaches are limited. To improve our understanding of the pathophysiology, we studied a porcine IHF model.MethodsIn pigs, IHF was induced by balloon occlusion of the left anterior descending artery for 90 min. After 30 days of reperfusion, invasive haemodynamic measurements and electrophysiological studies were performed. Masson trichrome and immunofluorescence staining were conducted to assess interstitial fibrosis and myofibroblast activation in different heart regions.ResultsAfter 30 days of reperfusion, heart failure with significantly reduced ejection fraction (left anterior obique 30°, 34.78 ± 3.29% [IHF] vs. 62.03 ± 2.36% [control], p < .001; anterior–posterior 0°, 29.16 ± 3.61% vs. 59.54 ± 1.09%, p < .01) was observed. These pigs showed a significantly higher susceptibility to AF (33.90% [IHF] vs. 12.98% [control], p < .05). Histological assessment revealed aggravated fibrosis in atrial appendages but not in atrial free walls in IHF pigs (11.13 ± 1.44% vs. 5.99 ± .86%, p < .01 [LAA], 8.28 ± .56% vs. 6.01 ± .35%, p < .01 [RAA]), which was paralleled by enhanced myofibroblast activation (12.09 ± .65% vs. 9.00 ± .94%, p < .05 [LAA], 14.37 ± .60% vs. 10.30 ± 1.41%, p < .05 [RAA]). Correlation analysis indicated that not fibrosis per se but its cross‐regional heterogeneous distribution across the left atrium was associated with AF susceptibility (r = .6344, p < .01).ConclusionOur results suggest that left atrial cross‐regional fibrosis difference rather than overall fibrosis level is associated with IHF‐related AF susceptibility, presumably by establishing local conduction disturbances and heterogeneity.

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A practical guide to setting up pig models for cardiovascular catheterization, electrophysiological assessment and heart disease research

Cited by 17 publications

References 49 publications

Cardiac Macrophages and Their Effects on Arrhythmogenesis

Cardiac Macrophages and Their Effects on Arrhythmogenesis

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

Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure

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