Abstract
BackgroundThe cardiac regenerative potential of newly developed therapies is traditionally evaluated in rodent models of surgically induced myocardial ischemia. A generally accepted key parameter for determining the success of the applied therapy is the infarct size. Although regarded as a gold standard method for infarct size estimation in heart ischemia, histological planimetry is time-consuming and highly variable amongst studies. The purpose of this work is to contribute towards the standardization and simplification of infarct size assessment by providing free access to a novel semi-automated software tool. The acronym MIQuant was attributed to this application.Methodology/Principal FindingsMice were subject to permanent coronary artery ligation and the size of chronic infarcts was estimated by area and midline-length methods using manual planimetry and with MIQuant. Repeatability and reproducibility of MIQuant scores were verified. The validation showed high correlation (r midline length = 0.981; r area = 0.970 ) and agreement (Bland-Altman analysis), free from bias for midline length and negligible bias of 1.21% to 3.72% for area quantification. Further analysis demonstrated that MIQuant reduced by 4.5-fold the time spent on the analysis and, importantly, MIQuant effectiveness is independent of user proficiency. The results indicate that MIQuant can be regarded as a better alternative to manual measurement.ConclusionsWe conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification. The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, therefore, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies.
Highlights
Cardiovascular disease is a leading cause of morbidity and mortality worldwide
We conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification
The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies
Summary
Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Heart failure due to ischemic coronary artery disease is currently the most common cardiac disorder and it correlates with a worse prognosis [1,2]. The physiological, histological and molecular changes associated with clinical ischemic heart disease have been clarified with the use of experimental models of myocardial infarction (MI) developed in both large animals, including dogs and swine, as well as in small rodents [3,4]. The latter are more applicable for high-throughput screening of novel therapeutic approaches, due to the easy maintenance, short reproductive cycle and to the latest advances in gene-targeting and transgenic technologies.
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