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Salt and Angiotensin II Treatment Induces Fluid Congestion and Heart Failure with Increased Mortality in Balb/C Mice but Not in C57BL/6J
Author(s) -
Joensson Sofia Tora,
BecriovicAgic Mediha,
Hulström Michael
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.962.6
Subject(s) - heart failure , medicine , angiotensin ii , blood pressure , stroke volume , heart rate , cardiology , cardiac output , sodium , renal function , excretion , cardiac function curve , endocrinology , chemistry , organic chemistry
Heart and kidney failure causes many hospitalizations, and is associated with high mortality rate. We have previously shown that 3% sodium diet and Angiotensin II (0.5 μg/min/kg) leads to clinical signs of heart failure with decreased blood pressure, edema and mortality in Balb/C while C57BL/6J are protected. The aim of the present investigation was to study heart function using left ventricular catheterization and to formally analyze mortality using meta‐analysis across all our studies. Mice were treated with a 3% sodium diet and AngII (0.5 μg/min/kg) using Alzet osmotic pumps for four days. Left ventricular catheterization showed lower heart rate and cardiac output in Balb/C (596±9.8 bpm, 7.1±0.74 ml/min) compared to C57BL/6J (517±6.2 bpm, 5.2±0.29 ml/min p<0.05) after Salt+AngII treatment. Stroke volume was lower in Balb/C treated with Salt+AngII compared to control treatment, but no difference was seen in C57BL/6J. The results were reproduced using echocardiography, which also showed a diastolic dysfunction. However, compliance as measured using the pressure volume relationship was not affected. This may be consistent with a fluid congestion and right heart failure as Balb/C show a lower urine output (0.24±0.04 vs. 0.46±0.02 ml/h, p<0.001) and sodium excretion (2.7±0.5 vs.3.5±0.3, p<0.05) with the combination treatment in spite of similar intake. Meta‐analysis of the mortality of 121 animals from four different experimental series showed a relative risk of 0.16 (95% CI 0.05–0.49) in favor of C57BL/6J after combination treatment with high‐sodium diet and AngII. This provides a rigorous statistical analysis of our observation that Balb/C is much more susceptible to heart failure. Similar analysis of sodium diet (n=96, RR 0.3, 95% CI 0.04–2.54), or AngII treatment alone (n= 83, RR 0.4, 95% CI 0.12–1.36) showed no significant difference. In conclusion, Balb/C mice have reduced cardiac function compared to C57BL/6J when treated with Salt and AngII, which leads to a higher mortality in Balb/C mice. Support or Funding Information Swedish Heart‐Lung foundation, Ake Wiberg foundation, Swedish Society for Medical Research