Large Animal Models of Ischemic Cardiomyopathy: Are They Enough to Bridge the Translational Gap?

Nguyen, Patricia K.; Wu, Joseph C.

doi:10.1007/s12350-015-0078-7

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…In addition to the above rat AMI model exerting a significant cardio-protective effect against IRI, a porcine AMI model, bearing a high similarity in coronary arterial structure and cardiac kinetics to human [ 32 , 33 , 34 , 35 , 36 ], was then established for further assessment of DBPR807. According to the experimental protocol shown in Figure 5 A, a single dose of DBPR807 (3 mg/kg, IV) was injected 30 min before LAD artery reperfusion during 90-min balloon occlusion.…”

Section: Resultsmentioning

confidence: 99%

Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention

Yeh

Lee

Song

et al. 2022

IJMS

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CXCR4 antagonists have been claimed to reduce mortality after myocardial infarction in myocardial infarction (MI) animals, presumably due to suppressing inflammatory responses caused by myocardial ischemia-reperfusion injury, thus, subsequently facilitating tissue repair and cardiac function recovery. This study aims to determine whether a newly designed CXCR4 antagonist DBPR807 could exert better vascular-protective effects than other clinical counterparts (e.g., AMD3100) to alleviate cardiac damage further exacerbated by reperfusion. Consequently, we find that instead of traditional continuous treatment or multiple-dose treatment at different intervals of time, a single-dose treatment of DBPR807 before reperfusion in MI animals could attenuate inflammation via protecting oxidative stress damage and preserve vascular/capillary density and integrity via mobilizing endothelial progenitor cells, leading to a desirable fibrosis reduction and recovery of cardiac function, as evaluated with the LVEF (left ventricular ejection fraction) in infarcted hearts in rats and mini-pigs, respectively. Thus, it is highly suggested that CXCR4 antagonists should be given at a single high dose prior to reperfusion to provide the maximal cardiac functional improvement. Based on its favorable efficacy and safety profiles indicated in tested animals, DBPR807 has a great potential to serve as an adjunctive medicine for percutaneous coronary intervention (PCI) therapies in acute MI patients.

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Section: Resultsmentioning

confidence: 99%

Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention

Yeh

Lee

Song

et al. 2022

IJMS

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“…In MI research, it is essential to correctly identify the perfusion and coronary collateral circulation systems in the animal of choice, as the variations in these structures across animals can significantly affect the early and progressive response to ischemia ( Harken et al, 1981 ; Hill and Iaizzo, 2009 ). In this regard, swine and ovine models are preferred to smaller animals, such as rodents and canines, as their coronary arterial structure and scant collateral arteries resemble those of humans, which allows for the creation of predictable infarct size at a preferred location in the myocardium ( Dixon and Spinale, 2009 ; Nguyen and Wu, 2015 ). Moreover, swine, sheep, and human myocardia share high degrees of similarities in cardiac kinetics ( Milani-Nejad and Janssen, 2014 ) and healing characteristics following injury ( Lelovas et al, 2014 ).…”

Section: Reviewmentioning

confidence: 99%

Current Status and Limitations of Myocardial Infarction Large Animal Models in Cardiovascular Translational Research

Shin

Shudo

2021

Front. Bioeng. Biotechnol.

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Establishing an appropriate disease model that mimics the complexities of human cardiovascular disease is critical for evaluating the clinical efficacy and translation success. The multifaceted and complex nature of human ischemic heart disease is difficult to recapitulate in animal models. This difficulty is often compounded by the methodological biases introduced in animal studies. Considerable variations across animal species, modifications made in surgical procedures, and inadequate randomization, sample size calculation, blinding, and heterogeneity of animal models used often produce preclinical cardiovascular research that looks promising but is irreproducible and not translatable. Moreover, many published papers are not transparent enough for other investigators to verify the feasibility of the studies and the therapeutics’ efficacy. Unfortunately, successful translation of these innovative therapies in such a closed and biased research is difficult. This review discusses some challenges in current preclinical myocardial infarction research, focusing on the following three major inhibitors for its successful translation: Inappropriate disease model, frequent modifications to surgical procedures, and insufficient reporting transparency.

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“…The first step is the selection of a suitable animal model that produces transferable results for future human clinical applications. In many cardiac surgery studies, pig models have been established due to their special anatomical and physiological similarities to the human heart [ 13 ]. Thus, not only heart valves and coronary care are comparable, but also the hemodynamics of the circulatory system.…”

Section: Clinical Relevance Of Data Analyzing Cardioplegic Solutions In Pig Modelsmentioning

confidence: 99%

Relevance and Recommendations for the Application of Cardioplegic Solutions in Cardiopulmonary Bypass Surgery in Pigs

et al. 2021

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Cardioplegic solutions play a major role in cardiac surgery due to the fact that they create a silent operating field and protect the myocardium against ischemia and reperfusion injury. For studies on cardioplegic solutions, it is important to compare their effects and to have a valid platform for preclinical testing of new cardioplegic solutions and their additives. Due to the strong anatomical and physiological cardiovascular similarities between pigs and humans, porcine models are suitable for investigating the effects of cardioplegic solutions. This review provides an overview of the results of the application of cardioplegic solutions in adult or pediatric pig models over the past 25 years. The advantages, disadvantages, limitations, and refinement strategies of these models are discussed.

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Large Animal Models of Ischemic Cardiomyopathy: Are They Enough to Bridge the Translational Gap?

Cited by 6 publications

References 40 publications

Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention

Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention

Current Status and Limitations of Myocardial Infarction Large Animal Models in Cardiovascular Translational Research

Relevance and Recommendations for the Application of Cardioplegic Solutions in Cardiopulmonary Bypass Surgery in Pigs

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