Table 1.
Hemodynamic, MRI and Histological Measurements at Baseline and Follow‐Up in Mice Treated With l‐NAME and With or Without Spironolactone Pre‐Treatment
| Baseline | Follow‐Up (7 Weeks) | |||||||
|---|---|---|---|---|---|---|---|---|
| Placebo (n=14) | l‐NAME (n=22) | l‐NAME+S (n=21) | P Value | Placebo (n=14) | l‐NAME (n=17) | l‐NAME+S (n=18) | P Value | |
| Body weight, g | 37.6±2.5 | 37.1±2.6 | 38.8±2.16 | 0.02 | 44.28±4.5** | 40±2.0**,†† | 43±3.6** | 0.01 |
| HR, bpm | 511±112 | 502±89 | 478±88 | 0.35 | 472±60 | 447±48* | 474±51 | 0.13 |
| Mean arterial blood pressure, mm Hg | 91.0±8.0 | 86.8±7.4 | 87.0±6.8 | 0.93 | 89.2±6.4 | 124±6.1**,†† | 107±5.3** | <0.001 |
| MRI | ||||||||
| LVEF, % | 57.8±3.7 | 59.7±3.34 | 60.0±3.65 | 0.84 | 60.3±3.2 | 51.3±8.2**,†† | 52.7±7.5**,†† | 0.63 |
| LVEDV, μL | 128±30.1 | 102±9.4†† | 99.3±6.1†† | 0.46 | 111±26.2* | 118±34* | 90±24† | 0.01 |
| LVESV, μL | 54±13.1 | 41.1±5.5†† | 39.9±5.6†† | 0.55 | 44±12.0* | 57 ±19**,†† | 44±16 | 0.04 |
| LVmass, μg | 94.5±16.3 | 91.7±12.2 | 88.2±11.8 | 0.46 | 98.5±14.4 | 163±19**,†† | 96 ±13 | <0.001 |
| LV mass‐to‐volume ratio | 0.77±0.17 | 0.90±0.12 | 0.88±0.09 | 0.54 | 0.94±0.29* | 1.47±0.38**,†† | 1.14±0.33**,† | 0.01 |
| LV mass index to body weight, μg/g | 3.40±0.79 | 2.47±0.31 | 2.27±0.23 | 0.08 | 2.54±0.69* | 4.07±0.42**,†† | 2.30±0.36 | <0.001 |
| MRI extracellular volume fraction (ECV) | 0.27±0.03 | 0.27±0.04 | 0.28±0.05 | 0.59 | 0.26±0.03 | 0.43±0.09**,†† | 0.25±0.03 | <0.001 |
| MRI intracellular life time of water, s | 0.14±0.07 | 0.17±0.09 | 0.16±0.06 | 0.57 | 0.18±0.08 | 0.42±0.11**,†† | 0.12±0.05 | <0.001 |
| Histology | ||||||||
| Connective tissue fraction (histology) [%] | — | — | — | — | 2.6±0.6% | 8.5±1.6%†† | 2.7±0.8% | <0.001 |
| Cardiomyocyte area, μm2/103 | — | — | — | — | 17.0±1.4 | 23.9±2.6†† | 18.4±1.6 | <0.001 |
| Volume‐to‐surface ratio | — | — | — | — | 24.7±1.5 | 32.1±1.9†† | 25.3±1.4 | <0.001 |
| Cardiomyocyte volume by histology, 104×μm3 | — | — | — | — | 42±6 | 77±13†† | 47±6 | <0.001 |
Column denoted by “P value” shows P‐values for l‐NAME vs l‐NAME+S. All P values for variables with repeated measurements (ie, baseline and follow‐up measurements) were obtained from one and the same linear mixed effects model for the variable, which had study (baseline or follow‐up), animal group, and their interaction as fixed effects. For the histological variables with only one measurement per animal P values were obtained by Tukey's “Honest Significant Difference” Method. Data for placebo group are for reference, were part of previous publication, and were included in the analysis with mixed effects models. LVEF indicates left ventricular ejection fraction; l‐NAME, Nω–nitro‐l‐arginine‐methyl‐ester; LVEDV, left ventricular end‐diastolic volume; LVESV, left ventricular end‐systolic volume; S, spironolactone.
For comparisons of follow‐up vs baseline, *P<0.05 and **P<0.01.
For comparisons at baseline or follow‐up vs placebo group †P<0.05 and ††P<0.01 for l‐NAME and l‐NAME+S groups.