TY - JOUR
T1 - Long-term severe diabetes only leads to mild cardiac diastolic dysfunction in Zucker diabetic fatty rats
AU - Daniels, Anneleen
AU - Linz, Dominik
AU - van Bilsen, Marc
AU - Ruetten, Hartmut
AU - Sadowski, Thorsten
AU - Ruf, Sven
AU - Juretschke, Hans-Paul
AU - Neumann-Haefelin, Claudia
AU - Munts, Chantal
AU - van der Vusse, Ger J.
AU - van Nieuwenhoven, Frans A.
PY - 2012/2
Y1 - 2012/2
N2 - Aims Type 2 diabetes mellitus (DM) leads to cardiac dysfunction irrespective of hypertension and coronary artery disease; this is called diabetic cardiomyopathy. Here, we investigated the severity of diabetic cardiomyopathy and myocardial remodelling in aged Zucker diabetic fatty (ZDF) rats. Methods and results Body weight, blood glucose and glycated haemoglobin (Hb(A1c)) levels, and urinary albumin excretion were monitored regularly in ZDF rats (n = 19) and control littermates (n = 19) up to age 45 weeks. ZDF rats were severely diabetic during the entire study period and demonstrated decreased body and heart weights at sacrifice. Left ventricular (LV) function was determined using magnetic resonance imaging (MRI) at age 44 weeks and revealed similar LV ejection fraction and cardiac output index in control and ZDF rats, indicating preserved systolic function. LV pressure characteristics assessed at age 45 weeks showed significant, but mild elevations of LV end-diastolic pressure (+45%) and relaxation time constant Tau (+54%) in ZDF rats, indicating diastolic dysfunction. Histological analyses revealed a significantly increased LV collagen content (+50%), but no cardiomyocyte hypertrophy in ZDF rats. Conclusion The present study clearly shows that long term, severe DM in 45-week-old ZDF rats resulted in relatively mild impairment of diastolic LV function, whereas systolic function was well preserved. These data do not support the notion that diabetes per se is a critical factor in the induction of a clinically relevant degree of cardiac dysfunction. Co-morbidities such as hypertension and coronary artery disease probably have larger impacts on myocardial function in diabetic individuals.
AB - Aims Type 2 diabetes mellitus (DM) leads to cardiac dysfunction irrespective of hypertension and coronary artery disease; this is called diabetic cardiomyopathy. Here, we investigated the severity of diabetic cardiomyopathy and myocardial remodelling in aged Zucker diabetic fatty (ZDF) rats. Methods and results Body weight, blood glucose and glycated haemoglobin (Hb(A1c)) levels, and urinary albumin excretion were monitored regularly in ZDF rats (n = 19) and control littermates (n = 19) up to age 45 weeks. ZDF rats were severely diabetic during the entire study period and demonstrated decreased body and heart weights at sacrifice. Left ventricular (LV) function was determined using magnetic resonance imaging (MRI) at age 44 weeks and revealed similar LV ejection fraction and cardiac output index in control and ZDF rats, indicating preserved systolic function. LV pressure characteristics assessed at age 45 weeks showed significant, but mild elevations of LV end-diastolic pressure (+45%) and relaxation time constant Tau (+54%) in ZDF rats, indicating diastolic dysfunction. Histological analyses revealed a significantly increased LV collagen content (+50%), but no cardiomyocyte hypertrophy in ZDF rats. Conclusion The present study clearly shows that long term, severe DM in 45-week-old ZDF rats resulted in relatively mild impairment of diastolic LV function, whereas systolic function was well preserved. These data do not support the notion that diabetes per se is a critical factor in the induction of a clinically relevant degree of cardiac dysfunction. Co-morbidities such as hypertension and coronary artery disease probably have larger impacts on myocardial function in diabetic individuals.
KW - Diabetes mellitus
KW - Cardiac function
KW - Myocardial remodelling
KW - Cardiac fibrosis
U2 - 10.1093/eurjhf/hfr166
DO - 10.1093/eurjhf/hfr166
M3 - Article
C2 - 22253456
SN - 1388-9842
VL - 14
SP - 193
EP - 201
JO - European journal of heart failure
JF - European journal of heart failure
IS - 2
ER -