TNFalpha and NFkB activation are associated with functional alterations in heart of anemic iron-deficient rats. A tissue Doppler imaging analysis

TOBLLI JE; GIANI JF; MUÑOZ MC; DOMINICI FP; RIVAS M

MUNICH, GERMANY

Congreso; EUROPEAN SOCIETY OF CARDIOLOGY CONGRESS 2008; 2008

EUROPEAN SOCIETY OF CARDIOLOGY

Iron deficiency (ID) is the most common nutritional deficiency worldwide. Furthermore, ID causes not only anemia but also cardiomyopathy. Additionally, anemia is a significant predictor of poor outcome in patients with heart failure. In this study we evaluated functional and inflammatory parameters in heart of a rat model of ID. Sprague-Dawley rats in two groups: Group-A (n=12) anemic and Group-B (n=12) non-anemic. Group-A received an iron deficient diet for 16 weeks after weaning and Group-B with standard rat chow. Hemoglobin (Hb) and serum iron (SI) were evaluated throughout the study. Echocardiography was performed without anesthesia. The end-diastolic left ventricular dimension (LVDd), end-systolic left ventricular dimension (LVDs), diastolic interventricular sepal thickness (IVS), diastolic left ventricular posterior wall thickness (LVPW) and LV fractional shortening (FS) were evaluated. A tissue Doppler Imaging (TDI) was performed to measure s (systolic) wave and e wave (early diastolic filling). All rats were killed at the end of the 16th week. NFkB(p65) total protein and NFkB(p65) phosphorylation (NFkB(p65) p) as well as TNF-alpha were determined by western blot in heart homogenates. Data are expressed as mean ± SD in arbitrary units. Results: Group-A vs. Group-B: 1-Hb (g/dl): 9.3±0.5 vs. 15.4±0.4 p<0.01; 2-SI (mcg/dl) 34.7±8.8 vs. 147.5±17.4 p<0.01.The heart from anemic animals presented an increase in: 1-NFkB (p65) total protein (130.5±29.2 vs. 102.8±4.8 p<0.03); 2- NFkB(p65)p (216.8±56.0 vs. 73.2±11.0 p<0.01); and 3-TNF-alpha protein  (244.3± 45.0 vs. 89.5±9.9 p<0.02), with respect to non anemic rats. Echocardiography: (Mean ± SD). Group A vs. Group B: 1-Heart rate (beat/min)= 585±20* vs. 493±11; 2-LVSd (mm)= 3.1±0.4* vs. 2.1±0.2; 3-LVDd (mm)= 5.9±0.3* vs. 4.7±0.5; 4-LVPW (mm)= 1.5±0.1* vs. 1.1±0.1; 5-IVS (mm)= 1.6±0.1* vs. 1.2±0.1; 6-FS (%)= 45.7±6.1* vs. 53.9±3.6. Tissue Doppler Imaging: Group A vs. Group B. 1-s wave (cm/s)= 22.3±5.8* vs. 34.6±3.4; 8-e wave (cm/s)= 35.0±4.2* vs. 62.5±3.2. (* p<0.01). There was a significant correlation between 1-Hb and NFkB(p65)p (r=-0.76 p<0.01) Hb and TNFalpha (r=-0.85 p<0.01); 2-SI and NFkB(p65)p (r=-0.84 p<0.01); SI and TNFalpha (r=-0.81 p<0.01); 3-SF% and NFkB(p65)p (r=-0.75 p<0.01); FS% and TNFalpha (r=-0.68 p<0.02); 4-e wave and NFkB(p65)p (r=-0.73 p<0.01); e wave and TNFalpha (r=-0.83 p<0.01). In conclusion, anemic ID rats presented an enlargement of LV dimensions with systolic and diastolic dysfunction versus non-anemic rats. These alterations seem to be associated with the activation of NFkB pathway and an increase in TNFalpha expression in heart.