A Model of Blood Component–Heart Interaction in Cardiac Ischemia–Reperfusion Injury using a Langendorff-Based Ex Vivo Assay

2019 ◽  
Vol 25 (2) ◽  
pp. 164-173 ◽  
Author(s):  
Johanna M. Muessig ◽  
Sema Kaya ◽  
Luise Moellhoff ◽  
Johanna Noelle ◽  
Leonie Hidalgo Pareja ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Function ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiac Ischemia ◽  
Transfer Model ◽  
Blood Components ◽  
The Impact ◽  
Human Rbcs

Introduction: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide. Cellular interactions of red blood cells (RBCs) and platelets with endothelial cells and cardiomyocytes play a crucial role in cardiac ischemia/reperfusion (I/R) injury. However, addressing the specific impact of such cell-to-cell interactions in commonly employed in vivo models of cardiac I/R injury is challenging due to overlap of neuronal, hormonal, and immunological pathways. This study aimed to refine a Langendorff-based ex vivo transfer model to evaluate the impact of specific blood components on cardiac I/R injury. Material and methods: Murine whole blood, defined murine blood components (RBCs, platelet-rich plasma [PRP], and platelet-poor plasma [PPP], respectively) as well as human RBCs were loaded to the coronary system of isolated murine hearts in a Langendorff system before initiating global ischemia for 40 minutes. Following 60 minutes of reperfusion with Krebs Henseleit Buffer, left ventricular function and coronary flow were assessed. Infarct size was determined by specific histological staining following 120 minutes of reperfusion. Results: Loading of murine whole blood to the coronary system of isolated murine hearts at the beginning of 40 minutes of global ischemia improved left ventricular function after 60 minutes of reperfusion and reduced the infarct size in comparison to buffer-treated controls. Similarly, isolated murine RBCs, PRP, and PPP mediated a protective effect in the cardiac I/R model. Furthermore, human RBCs showed a comparable protective capacity as murine RBCs. Conclusion: This Langendorff-based transfer model of cardiac I/R injury is a feasible, time-, and cost-effective model to evaluate the impact of blood components on myocardial infarction. The presented method facilitates loading of blood components of genetically modified mice to murine hearts of a different mouse strain, thus complementing time- and cost-intensive chimeric models and contributing to the development of novel targeted therapies.

scholarly journals Limb remote ischemia per-conditioning protects the heart against ischemia–reperfusion injury through the opioid system in rats

2018 ◽  
Vol 96 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Li Zhang ◽  
Hui Guo ◽  
Fang Yuan ◽  
Zeng-chao Hong ◽  
Yan-ming Tian ◽  
...  
Keyword(s):  
Protein Expression ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiac Ischemia ◽  
Cardiac Protection ◽  
Expression Levels ◽  
Infarct Area

Remote ischemia per-conditioning (RPerC) has been demonstrated to have cardiac protection, but the underlying mechanism remains unclear. This study aimed to investigate the mechanism underlying cardiac protection of RPerC. Adult male Sprague–Dawley rats were used in this study. Cardiac ischemia/reperfusion (I/R) was induced by 30 min of occlusion and 3 h of reperfusion of the left anterior descending coronary artery. RPerC were performed by 5 min of occlusion of the right femoral artery followed by 5 min of reperfusion for three times during cardiac ischemia. The hemodynamics, left ventricular function, arrhythmia, and infarct area were measured. Protein expression levels of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), protein kinase C-ε (PKCε), and PKCδ in the myocardium were assayed. During I/R, systolic artery pressure and left ventricular function were decreased, infarct area was increased, and arrhythmia score was increased (P < 0.05). However, changes of the above parameters were significantly attenuated in RPerC-treated rats compared with control rats (P < 0.05). The cardiac protective effects of RPerC were prevented by naloxone or glibenclamide. Also, RPerC increased the protein expression levels of eNOS, iNOS, PKCε, and PKCδ in the myocardium compared with control rats. These effects were blocked by naloxone, an opioid receptor antagonist, and glibenclamide, an ATP-sensitive K+ channel blocker (KATP). In summary, this study suggests that RPerC protects the heart against I/R injury through activation of opioid receptors and the NO–PKC–KATP channel signaling pathways.

The Impact Of Lifelong Physical Activity And Myocardial Infarction On Left Ventricular Function

2015 ◽  
Vol 47 ◽  
pp. 853
Author(s):  
Maria T.E. Hopman ◽  
Martijn F.H. Maessen ◽  
Rik H.G. Hansen ◽  
Dick H.J. Thijssen ◽  
Arie van Dijk ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
The Impact

scholarly journals Macrophage depletion impairs adequate cardiac repair in mouse models of myocardial infarction with variable transmurality - insights from multimodality molecular imaging

2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
A Hess ◽  
LBN Langer ◽  
TL Ross ◽  
FM Bengel ◽  
JT Thackeray
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Cardiac Repair ◽  
Lv Function ◽  
Cardiac Inflammation ◽  
Macrophage Depletion ◽  
Pet Ct ◽  
Ex Vivo Autoradiography ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG) Introduction Balanced myocardial tissue inflammation following acute myocardial infarction (MI) is needed for optimal cardiac repair. Macrophages contribute to wound healing, but may also be deleterious. Purpose We investigated the impact of macrophage depletion on early cardiac inflammation and later functional outcome in two models of MI with variable transmurality. Methods C57BL/6N mice received clodronate-liposomes for macrophage depletion (n = 49) or control PBS-liposomes (n = 23). After 24h, mice underwent permanent occlusion (PO) or transient ischemia-reperfusion (I/R, 60min) of the left coronary artery or sham surgery. Cardiac inflammation was assessed on MI + 1d, 3d, and 7d by CXCR4-targeted PET/CT using 68Ga-pentixafor. 99mTc-sestamibi SPECT/CT and cardiac magnetic resonance (CMR) calculated infarct sizes and left ventricular (LV) function at 1wk and 6wks. 18F-NaF PET/CT measured tissue microcalcification at 4wks. Imaging signals were validated by ex vivo autoradiography and immunohistochemistry. Results Clodronate macrophage depletion did not affect infarct size compared to PBS, but perfusion defects at 6wks were significantly larger after PO compared to I/R (%LV, 32 ± 11 vs 14 ± 10, p = 0.01). In both models, infarct CXCR4 expression was higher after macrophage depletion vs PBS at all timepoints (%injected dose (ID)/g; d3: PO: 1.4 ± 0.2 vs 0.9 ± 0.1; I/R: 1.4 ± 0.2 vs 1.0 ± 0.02; p &lt; 0.05), and confirmed by ex vivo autoradiography. Immunostaining demonstrated fewer macrophages and higher neutrophil content within the myocardium after macrophage depletion vs PBS at 1d, 3d, and 7d post-MI. Acute LV rupture after PO was more frequent in macrophage-depleted than PBS mice (37% vs 17%). Conversely, surviving PO mice showed a similarly impaired ejection fraction (EF) after macrophage depletion vs PBS at 6wks (%, 32 ± 9 vs 32 ± 11, p = 0.84). No acute LV rupture was observed after I/R, but macrophage depletion led to worse EF (%, 42 ± 11 vs 54 ± 3, p = 0.1). Macrophage-depleted mice exhibited a dense intracavity thrombus adherent to the infarct wall after either injury, as visualized on CMR at 1wk. 18F-NaF PET identified active calcification localized to the thrombus region 4wks after MI, which was colocalized to CT opaque regions at 6wks. Conclusion Macrophage depletion impairs cardiac repair via several mechanisms including neutrophil-dominated inflammation, LV thrombus formation and tissue calcification. This observation underscores the requirement of macrophages for effective healing and may explain adverse response to broad anti-inflammatory therapy in myocardial ischemia.

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