scholarly journals Translational failure of anti-inflammatory compounds for myocardial infarction: a meta-analysis of large animal models

2015 ◽  
Vol 109 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Gerardus P. J. van Hout ◽  
Sanne J. Jansen of Lorkeers ◽  
Kimberly E. Wever ◽  
Emily S. Sena ◽  
Lisanne H. J. A. Kouwenberg ◽  
...  
2014 ◽  
Vol 1 (1) ◽  
pp. e00004 ◽  
Author(s):  
G.P.J. van Hout ◽  
S.J. Jansen of Lorkeers ◽  
K.E. Wever ◽  
E.S. Sena ◽  
W.W. van Solinge ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Marc-Antoine Isorni ◽  
Amaury Casanova ◽  
Julie Piquet ◽  
Valérie Bellamy ◽  
Charly Pignon ◽  
...  

Objective.To develop a rabbit model of closed-chest catheter-induced myocardial infarction.Background.Limitations of rodent and large animal models justify the search for clinically relevant alternatives.Methods.Microcatheterization of the heart was performed in 47 anesthetized 3-4 kg New Zealand rabbits to test five techniques of myocardial ischemia: free coils (n=4), interlocking coils (n=4), thrombogenic gelatin sponge (n=4), balloon occlusion (n=4), and alcohol injection (n=8). In order to limit ventricular fibrillation, an antiarrhythmic protocol was implemented, with beta-blockers/amiodarone before and xylocaine infusion during the procedure. Clinical, angiographic, and echographic data were gathered. End points included demonstration of vessel occlusion (TIMI flow grades 0 and 1 on the angiogram), impairment of left ventricular function at 2 weeks after procedure (by echocardiography), and pathologically confirmed myocardial infarction.Results.The best arterial access was determined to be through the right carotid artery. The internal mammary guiding catheter 4-Fr was selected as the optimal device for selective intracoronary injection. Free coils deployed prematurely and tended to prolapse into the aorta. Interlocking coils did not deploy completely and failed to provide reliable results. Gelatin sponge was difficult to handle, adhered to the catheter, and could not be clearly visualized by fluoroscopy. Balloon occlusion yielded inconsistent results. Alcohol injection was the most efficient and reproducible method for inducing myocardial infarction (4 out of 6 animals), the extent of which could be fine-tuned by using a coaxial balloon catheter as a microcatheter (0.52 mm) to achieve a superselective injection of 0.2 mL of alcohol. This approach resulted in a 20% decrease in LVEF and infarcted myocardium was confirmed histologically.Conclusions.By following a stepwise approach, a minimally invasive, effective, and reproducible rabbit model of catheter-induced myocardial infarction has been developed which addresses the limitations of rodent experiments while avoiding the logistical and cost issues associated with large animal models.


2011 ◽  
Vol 91 (4) ◽  
pp. 649-658 ◽  
Author(s):  
T. I. G. van der Spoel ◽  
S. J. Jansen of Lorkeers ◽  
P. Agostoni ◽  
E. van Belle ◽  
M. Gyongyosi ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1836
Author(s):  
Daina Martínez-Falguera ◽  
Oriol Iborra-Egea ◽  
Carolina Gálvez-Montón

Myocardial infarction is the main driver of heart failure due to ischemia and subsequent cell death, and cell-based strategies have emerged as promising therapeutic methods to replace dead tissue in cardiovascular diseases. Research in this field has been dramatically advanced by the development of laboratory-induced pluripotent stem cells (iPSCs) that harbor the capability to become any cell type. Like other experimental strategies, stem cell therapy must meet multiple requirements before reaching the clinical trial phase, and in vivo models are indispensable for ensuring the safety of such novel therapies. Specifically, translational studies in large animal models are necessary to fully evaluate the therapeutic potential of this approach; to empirically determine the optimal combination of cell types, supplementary factors, and delivery methods to maximize efficacy; and to stringently assess safety. In the present review, we summarize the main strategies employed to generate iPSCs and differentiate them into cardiomyocytes in large animal species; the most critical differences between using small versus large animal models for cardiovascular studies; and the strategies that have been pursued regarding implanted cells’ stage of differentiation, origin, and technical application.


2011 ◽  
Vol 57 (14) ◽  
pp. E1011
Author(s):  
Tycho Van der Spoel ◽  
Sanne Jansen of Lorkeers ◽  
Pierfrancesco Agostoni ◽  
Eric Van Belle ◽  
Joost Sluijter ◽  
...  

2019 ◽  
Vol 316 (6) ◽  
pp. F1227-F1235 ◽  
Author(s):  
Yu Qi Lee ◽  
Emma L. Beckett ◽  
Dean V. Sculley ◽  
Kym M. Rae ◽  
Clare E. Collins ◽  
...  

Maternal undernutrition during pregnancy is prevalent across the globe, and the origins of many chronic diseases can be traced back to in utero conditions. This systematic review considers the current evidence in animal models regarding the relationship between maternal global nutrient restriction during pregnancy and offspring kidney structure and function. CINAHL, Cochrane, EMBASE, MEDLINE, and Scopus were searched to November 2017. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles were screened by two independent reviewers. Twenty-eight studies met the inclusion criteria: 16 studies were on rats, 9 on sheep, 2 on baboons, and 1 on goats. The majority of the rat studies had maternal global nutrient restriction during pregnancy at 50% of ad libitum while restriction for sheep and baboon studies ranged from 50% to 75%. Because of the heterogeneity of outcome measures and the large variation in the age of offspring at followup, no meta-analysis was possible. Common outcome measures included kidney weight, nephron number, glomerular size, glomerular filtration rate, and creatinine clearance. To date, there have been no studies assessing kidney function in large animal models. Most studies were rated as having a high or unknown risk of bias. The current body of evidence in animals suggests that exposure to maternal global nutrient restriction during pregnancy has detrimental effects on offspring kidney structure and function, such as lower kidney weight, lower nephron endowment, larger glomerular size, and lower glomerular filtration rate. Further long-term followup of studies in large animal models investigating kidney function through to adulthood are warranted.


Author(s):  
Hye Sook Shin ◽  
Heather Hyeyoon Shin ◽  
Yasuhiro Shudo

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.


Sign in / Sign up

Export Citation Format

Share Document