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LETTERS TO THE EDITOR
1University of Central Florida, Orlando, Florida; and 2University of Wisconsin, Madison, Wisconsin
REPLY: Dr. Lygate (5) has suggested that the variability observed in infarct size in the surgical mouse myocardial infarction model (10–70%) (1, 7) mandates larger sample sizes than used in our study (9). Although we agree that variable infarct size certainly occurs with this model, our presented data show clear, statistically significant differences with the given sample sizes. Our protocol may reduce variability in infarct size by careful attention to a proximal ligation of the left coronary immediately at the site where it emerges from under the left atrium as well as by eliminating mice that do not have a clear area of distal blanching of myocardium after immediate ligation (4, 8, 9). The more distal the ligation is made, the more the variability in coronary anatomy of the mouse heart impacts infarct size. Thus the referenced study by Patten et al. (7), which stated that the suture on the left coronary was placed approximately midway between the apex and base of the left ventricle, likely introduced greater variability in infarct size than we observed. Another study referenced by Dr. Lygate further makes this point in that Takagawa et al. (10) systematically created large infarctions by using proximal left coronary ligations (4 mm from apex) and small infarctions by distal ligations (2 mm from apex). We conclude that with careful attention to surgical technique, the range of infarct sizes can be much smaller than the 10–70% suggested by Dr. Lygate and that with the techniques used in our study, statistically significant results with the stated sample sizes were obtained.
Second, Dr. Lygate questions the validity of the infarct size measurements made at the mid-papillary muscle level. This approach is a common technique used in the literature, including a contemporary study (2). Although we certainly concede that absolute quantification of size of the infarction relative to the total left ventricle would require additional sampling, our purpose was to compare two groups of animals assessed in the same fashion at the mid-papillary level. This was the region where the samples were taken for assessment of apoptosis, so it was desirable to have the closest matched regions for apoptosis and infarct size measurements. Using this uniform sampling method, we observed statistically significant differences.
Finally, Dr. Lygate raises the question as to whether the decrease in apoptosis, hypertrophy, and fibrosis were direct effects of ESC treatment or simply reflected the reduction in infarct size. Dr. Lygate states that the extent of apoptosis correlates directly with infarct size and cites relevant literature (3, 7); however, these references simply look at apoptosis levels following infarction without intervention. A broader examination of the literature in which intervention groups are compared with control myocardial infarction groups reveals that a correlation between infarct size and the extent of apoptosis is oftentimes not present (2, 6). To begin to address this issue directly for apoptosis in our study, we provided data in Figure 1H (9) showing that there is not a simple correlation between infarct size and apoptotic nuclei and that the two groups of data are clearly separate. Nevertheless, we acknowledge that fully understanding the mechanisms underlying the observed effects will require substantial future studies.
FOOTNOTES
Address for reprint requests and other correspondence: D. K. Singla, College of Medicine, Biomolecular Sciences Center, Burnett School of Biomedical Science, Univ. of Central Florida, Orlando, FL 32816 (e-mail: dsingla{at}mail.ucf.edu)
REFERENCES
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