atrial-natriuretic-factor and Heart-Failure--Diastolic

Inherited dilated cardiomyopathy (DCM) is a progressive disease that often results in death from congestive heart failure (CHF) or sudden cardiac death (SCD). Mouse models with human DCM mutation are useful to investigate the developmental mechanisms of CHF and SCD, but knowledge of the severity of CHF in live mice is necessary. We aimed to diagnose CHF in live DCM model mice by measuring voluntary exercise using a running wheel and to determine causes of death in these mice.. A knock-in mouse with a mutation in cardiac troponin T (ΔK210) (DCM mouse), which results in frequent death with a t(1/2) of 70 to 90 days, was used as a DCM model. Until 2 months of age, average wheel-running activity was similar between wild-type and DCM mice (approximately 7 km/day). At approximately 3 months, some DCM mice demonstrated low running activity (LO: <1 km/day) while others maintained high running activity (HI: >5 km/day). In the LO group, the lung weight/body weight ratio was much higher than that in the other groups, and the lungs were infiltrated with hemosiderin-loaded alveolar macrophages. Furthermore, echocardiography showed more severe ventricular dilation and a lower ejection fraction, whereas Electrocardiography (ECG) revealed QRS widening. There were two patterns in the time courses of running activity before death in DCM mice: deaths with maintained activity and deaths with decreased activity.. Our results indicate that DCM mice with low running activity developed severe CHF and that running wheels are useful for detection of CHF in mouse models. We found that approximately half of ΔK210 DCM mice die suddenly before onset of CHF, whereas others develop CHF, deteriorate within 10 to 20 days, and die.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cause of Death; Disease Models, Animal; Electrocardiography; Fibrosis; Heart Failure, Diastolic; Humans; Lung; Mice; Mice, Transgenic; Myocardium; Natriuretic Peptide, Brain; Organ Size; Physical Conditioning, Animal; Running

Diastolic heart failure often coexists with atrial fibrillation (AF). Elevated plasma levels of natriuretic peptides are the left ventricular (LV) marker of diastolic dysfunction.. To evaluate the influence of sinus rhythm restoration on ANP and BNP levels in patients with normal and impaired LV diastolic function.. The study included 42 patients (19 men, 23 women), aged 58.6 +/- 8.2 years with non-valvular persistent AF with preserved LV systolic function who were successfully converted to sinus rhythm by DC cardioversion (CV) and maintained sinus rhythm for at least 30 days. On day 30 following CV in patients with sinus rhythm, Doppler echocardiography was performed to assess LV diastolic function. ECG, echocardiography, ANP and BNP plasma level measurements were made at baseline 24 h before CV and 24 h as well as 30 days after CV.. The average ANP level in the whole study group during AF was 254.9 +/- 79.9 pg/ml and the average BNP level was 113.6 +/- 49.1 pg/ml. There was an evident decrease in ANP/BNP serum concentration in all the patients after successful DC cardioversion. Measured on the 30th day after CV, ANP and BNP levels were 153.2 +/- 67.9 pg/ml and 61.9 +/- 25.1 pg/ml respectively (p < 0.001). Thirty days after CV normal LV diastolic function was diagnosed in 15 patients and in 27 patients impaired diastolic function: 20 with impaired LV relaxation and 7 with impaired LV compliance. The extent of natriuretic peptides drop was dependent on the LV diastolic function, being more substantial in the subgroup with impaired LV diastolic function. In the subgroup with LV diastolic dysfunction the average ANP serum concentration measured 30 days after conversion was reduced by 111.2 +/- 93.9 pg/ml (37%) (p < 0.001) and BNP level was reduced by 67.5 +/- 36.0 pg/ml (46%) (p < 0.001). In patients with normal diastolic function sinus rhythm restoration significantly influenced ANP level, while having no relevant effect on BNP plasma concentration. The average ANP reduction in this subgroup was 64.4 +/- 71.8 pg/ml (by 38%) and BNP reduction was 11.4 +/- 16.7 pg/ml (by 23%) (NS).. The drop in ANP and BNP plasma concentrations after conversion to sinus rhythm in patients with AF depends on the LV diastolic function. Restoration of sinus rhythm is associated with improvement of the heart's haemodynamics, especially in patients with impaired LV diastolic function, which may be inferred from the more pronounced decrease of BNP level after DC cardioversion in this subgroup, as compared to that with normal LV function.

Topics: Adult; Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Electric Countershock; Female; Heart Failure, Diastolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Dysfunction, Left