Evidence of sex differences in cancer‐related cardiac complications in mouse models of pancreatic and liver cancer

Figures

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  FIGURE 1. Schematic overview of the study workflow, electrocardiogram analysis, and histology.

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  FIGURE 2. Time domain analysis of HRV reveals higher variability in female cancer mice. (a) Representative electrocardiogram traces of female mice (left panels) and male mice (right panels) showing control (gray), pancreatic cancer (purple), and liver cancer (orange) study groups. (b) Poincaré plots for female (left panel) and male (right panel) mice show HRV in control (gray), pancreatic cancer (purple), and liver cancer (orange) study groups. (c) SD1, (d) SD2, (e) SD1/SD2 ratios, and (f) median heart rate are shown for each group, with female mice on the left and male mice on the right panels. A Nonparametric Wilcoxon Rank Sum test was used to determine statistical differences by comparing pancreatic and liver cancer groups to control at a significance level of p < 0.05. All data are shown as box‐and‐whiskers plots with upper and lower bars corresponding to the 25th and 75th percentiles and the middle bar to the median. Sample sizes were the following: control: male = 5 (61 recordings), female = 5 (75 recordings); pancreatic cancer: male = 5 (5 recordings), female = 9 (9 recordings); liver cancer: male = 5 (5 recordings), female = 7 (7 recordings). A.U., arbitrary unit; HRV, heart rate…

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  FIGURE 3. Frequency domain analysis of HRV reveals higher variability in female cancer mice. (a) Representative power spectral density (PSD) of female mice (left panels) and male mice (right panels) showing control (gray), pancreatic cancer (purple), and liver cancer (orange) study groups. (b) LF (0.1–1.5 Hz), (c) HF (1.5–4 Hz) bands, and (d) LF/HF ratios are shown for each group, with female mice on the left and male mice on the right panels. A Nonparametric Wilcoxon Rank Sum test was used to determine statistical differences by comparing pancreatic and liver cancer groups to control at a significance level of p < 0.05. All data are shown as box‐and‐whiskers plots with upper and lower bars corresponding to the 25th and 75th percentiles and the middle bar to the median. Sample sizes were the following: control: male = 5 (61 recordings), female = 5 (75 recordings); pancreatic cancer: male = 5 (5 recordings), female = 9 (9 recordings); liver cancer: male = 5 (5 recordings), female = 7 (7 recordings). HF, high frequency; LF, low frequency.

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  FIGURE 4. Structural changes quantification of Masson's trichrome staining. (a) The ratio of fibrosis (blue) to myocardium (pink) is shown for each chamber. A Nonparametric Wilcoxon Rank Sum test was used to determine statistical differences by comparing pancreatic and liver cancer groups to control at a significance level of p < 0.05. All data are shown as box‐and‐whiskers plots with upper and lower bars corresponding to the 25th and 75th percentiles and the middle bar to the median. Sample sizes were the following: control: male = 4 (RA—8, LA—8, RV—12, LV—12 images), female = 5 (RA—10, LA—10, RV—15, LV—15 images); pancreatic cancer: male = 3 (RA—6, LA—6, RV—9, LV—9 images), female = 10 (RA—1, LA—18, RV—30, LV—30 images); liver cancer: male = 3 (RA—6, LA—6, RV—9, LV—9 images), female = 9 (RA—18, LA—12, RV—27, LV—27 images). LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. (b) Representative images of Masson's trichrome staining cross‐sections of LV. The scale bar size is 200 μm.