We would like to thank the scientists at Charles River Research Models and Services for their critique of our report.5 Vendors of laboratory animals are in a unique position to thoroughly study the health of rodent colonies, and this type of effort would benefit both the company and the consumer. We reported the observation that hearts with concentric left ventricular (LV) hypertrophy and narrowed LV chambers are present in 38% of Sprague–Dawley rats. We are confident that this phenotype is worthy of description.
Dismissing our findings as a phenomenon of rigor mortis is a perfunctory explanation for the quantified differences that were seen in LV wall thickness and cardiomyocyte measurements between the Sprague–Dawley and Lewis rat hearts. Rigor mortis is a chemical change resulting in a stiffening of the body muscles as ATP is converted to ADP and lactic acid is produced lowering the cellular pH, promoting chemical bridges to form between actin and myosin, leading to the formation of rigor.4 Typically, the onset of rigor in humans is first observed 2 to 6 h following death and develops over the first 12 h. Rigor mortis in rat muscle is apparent from 6 to 24 h after death using scanning electron microscopy and the light microscopy by phosphotungstic acid-hematoxylin staining.7 However, we witnessed concentric LV wall thickening and slit-like LV chambers within minutes after euthanasia of Sprague–Dawley rats, well before rigor mortis would occur. Our necropsies were performed at room temperature, so rigor mortis would not be expected to cause “pseudohypertrophy” of the LV until 3 h postmortem based on the temperature.3 Furthermore, the hearts from the Sprague–Dawley and Lewis rats were handled in a similar manner. Therefore, the postmortem influence on each would be similar. If postmortem cardiomyocyte contraction was the underlying cause of the LV hypertrophy, both Lewis and Sprague–Dawley rats should have had similar LV free wall and LV chamber measurements, which was not the case. Therefore, we disagree with the scientists at Charles River Research Models and Services that postmortem contraction could have caused all of the evidence of myocardial thickening seen in the Sprague–Dawley rats in our study.
The low mortality associated with surgery reported by the scientists at Charles River Research Models and Services does not exclude the possibility of LV concentric hypertrophy in Sprague–Dawley rats. The lifespan of all commercially available rat strains and stocks has been declining, possibly due to interaction between genomic and environmental factors.6 Because laboratory rats are essential for research, ongoing efforts to monitor the health of rats are of paramount importance. We agree that studies using echocardiography and incorporating cardiac-weight to body-weight ratios should be conducted by objective laboratories to better characterize the pathophysiology of cardiac hypertrophy. Ultimately, thorough study of myocyte gene expression, cardiomyocyte apoptosis, defects in energy metabolism, or cardiac extracellular matrix composition may reveal the mechanisms underlying the cardiomyopathy in Sprague–Dawley rats.1,2
Letters to the Editor
Letters discuss material published in CM in the previous 3 issues. They can be submitted through email (journals@aalas.org) or by regular mail (9190 Crestwyn Hills Dr, Memphis, TN 38125). Letters are not necessarily acknowledged upon receipt nor are the authors necessarily consulted before publication. Whether published in full or part, letters are subject to editing for clarity and space. The authors of the cited article will generally be given an opportunity to respond in the same issue in which the letter is published.
Sincerely,
Ryan M McAdams, MD
Assistant Professor of Pediatrics, Department of Pediatrics University of Washington
Ronald J McPherson, PhD
Research Scientist, Department of Pediatrics University of Washington
Nazila M Dabestani
Student, Department of Pediatrics University of Washington
Christine A Gleason, MD
W Alan Hodson Endowed Chair in Pediatrics Professor of Pediatrics and Head, Department of Pediatrics University of Washington
Sandra E Juul, MD, PhD
Professor of Pediatrics, Department of Pediatrics University of Washington
References
- 1.Bernardo BC, Weeks KL, Pretorius L, McMullen JR. 2010. Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. Pharmacol Ther 128:191–227 [DOI] [PubMed] [Google Scholar]
- 2.Gupta S, Das B, Sen S. 2007. Cardiac hypertrophy: mechanisms and therapeutic opportunities. Antioxid Redox Signal 9:623–652 [DOI] [PubMed] [Google Scholar]
- 3.Krompecher T. 1981. Experimental evaluation of rigor mortis. V. Effect of various temperatures on the evolution of rigor mortis. Forensic Sci Int 17:19–26 [DOI] [PubMed] [Google Scholar]
- 4.Lee Goff M. 2009. Early post-mortem changes and stages of decomposition in exposed cadavers. Exp Appl Acarol 49:21–36 [DOI] [PubMed] [Google Scholar]
- 5.McAdams RM, McPherson RJ, Dabestani NM, Gleason CA, Juul SE. 2010. Left ventricular hypertrophy is prevalent in Sprague–Dawley rats. Comp Med 60:357–363 [PMC free article] [PubMed] [Google Scholar]
- 6.Nohynek GJ, Longeart L, Geffray B, Provost JP, Lodola A. 1993. Fat, frail, and dying young: survival, body weight, and pathology of the Charles River Sprague–Dawley-derived rat prior to and since the introduction of the VAFR variant in 1988. Hum Exp Toxicol 12:87–98 [DOI] [PubMed] [Google Scholar]
- 7.Zhigang L, Xufu Y, Fei X, Xuemei P. 1999. Morphological changes of rats muscles at various postmortem intervals by scanning electron microscopy. Chin Med Sci J 14:255–258 [PubMed] [Google Scholar]