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A novel method optimizing the normalization of cardiac parameters in small animal models: the importance of dimensional indexing.

Am J Physiol Heart Circ Physiol. 2019 Apr 12;:

Authors: Hagdorn QAJ, Bossers GPL, Koop AMC, Piek A, Eijgenraam TR, van der Feen DE, Silljé HHW, de Boer RA, Berger RMF

Abstract
AIMS: For indexing cardiac measures in small animal models, tibia length (TL) is a recommended surrogate for body weight (BW) that aims to avoid biases due to disease-induced BW changes. However, we question if indexing by TL is mathematically correct. This study aimed to investigate the relation between TL and BW, heart weight, ventricular weights and left ventricular diameter to optimize the current common practice of indexing cardiac parameters in small animal models.
METHODS AND RESULTS: In 29 healthy Wistar rats (age 5-34 weeks), and 116 healthy Black 6 mice (age 3-17 weeks) BW appeared to scale non-linearly to TL1, but linearly to TL3. Formulas for indexing cardiac weights were derived. To illustrate the effects of indexing, cardiac weights between the 50% with highest BW, and the 50% with lowest BW were compared. The non-indexed cardiac weights differed significantly between groups, as could be expected (p<0.001). However, after indexing by TL1, indexed cardiac weights remained significantly different between groups (p<0.001). Using the derived formulas for indexing, indexed cardiac weights were similar between groups.
CONCLUSIONS: In healthy rats and mice, BW and heart weights scale linearly to TL3. This indicates that not TL1, but TL3 is the optimal surrogate for BW. New formulas for indexing heart weight and isolated ventricular weights are provided, and we propose a concept in which cardiac parameters should not all be indexed to the same measure, but one-dimensional measures to BW1/3 or TL1, two-dimensional measures to BW2/3 or TL2 and three-dimensional measures to BW or TL3.

PMID: 30978120 [PubMed – as supplied by publisher]

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