How to improve the overall quality of cardiac morphometric data

By the mid-1990s, experts realized that drugs leading to improved ventricular remodeling were doing something remarkable in cardiac patients. The "age of cardiac remodeling" had begun. This created an experimental need for high-quality assessment of changes in cardiac tissue composition, including myocyte shape, myocardial fibrosis/collagen, and vascular remodeling. Many working in the field today have little or no training related to recognition of fixation artifacts or common errors associated with quantitative morphology. Unfortunately, such skills had become somewhat of a lost art during the ages of cardiac physiology in the mid-20th century and molecular biology, gaining prominence by the mid-1970s. Consequently, cardiac remodeling studies today are often seriously flawed to the point where data are not reproducible and subsequent researchers may be chasing the molecular basis of a nonexistent or erroneous phenotype. The current unacceptably high incidence of irreproducible data is a serious waste of time and resources as recently noted in comments by the National Institutes of Health director. The goal of this "how to" article is to share some lessons I have learned during nearly 40 years of assessing morphological changes in the heart. It is possible for any laboratory to routinely publish highly reproducible morphological data that stand the test of time and contribute to our fundamental knowledge of cardiac remodeling and the molecular mechanisms that drive it.