Td Nguyen

Echocardiography Alone Allows the Determination of Heart Failure Stages in Rats with Pressure Overload

BACKGROUND There is currently no standard for the assessment of contractile function in animals. We aimed to determine whether transthoracic echocardiography in rats with chronic pressure overload allows determining the stage of hypertrophy and heart failure (HF). METHODS Pressure overload was created by placement of a metal clip around the thoracic aorta at a weight of 40 to 50 g. After 1, 2, 6, 10, and 20 weeks, we performed echocardiography according to the American Heart Association guidelines (n = 26, four to six rats for each time point). We also obtained heart, lung, and body weights and regularly evaluated clinical signs of HF. RESULTS : Pressure overload caused significant hypertrophy within 1 week. Contractile function was normal until 6 weeks when diastolic dysfunction appeared. After 10 weeks of pressure overload, systolic function decreased. At 20 weeks, hearts were dilated and cardiac index was decreased. These findings correlated with increased lung-to-body weight ratio after 6 weeks and clinical signs of HF after 20 weeks. CONCLUSION Echocardiography alone allows the reproducible determination of HF stages after aortic constriction in rats.

OLEATE CONTROLS THE EFFECTS OF GLP-1 AND EXENDIN-4 ON MYOCARDIAL GLUCOSE UTILIZATION AND CONTRACTILE FUNCTION

Methods: Rat hearts were perfused with buffer containing only glucose (5mM) or glucose (5mM) and oleate (0.4mM) for 60 minutes in the working mode. After 30 minutes, GLP-1 or exendin-4 (0.5 nM or 5 nM) was added. We measured changes in cardiac GU ([2-3H] glucose) and GO ([U-14C] glucose). Results: In the absence of oleate, 5nM GLP-1 elevated GU (4.68±0.29 vs. 3.85±0.44 μmolglc/min/gdry, p<0.05) and GO (2.78±0.35 vs. 1.86±0 .4, p<0.01). Exendin-4 increased GO at both 0.5 nM (4.84±0.76 vs. 4.02±0.76 μmolglc/min/gdry, p<0.05) and 5nM (3.67±0.71 vs. 3.03±0.84 μmolglc/min/gdry, p<0.05). Neither GLP-1 nor exendin-4 showed any effect on cardiac power. However, in the presence of oleate, GLP-1 did not change glucose utilization and exendin-4 unexpectedly decreased GU at both 0.5nM (0.64±0.07 vs. 1.91±0.19 μmolglc/min/gdry, p<0.001) and 5nM (1±0.15 vs. 1.82±0.11, p<0.05). Besides, both 5nM GLP-1 (15.1±1.4 vs. 25.97±3.73 mW/gdry, p<0.05) and exendin-4 at 0.5 nM (25.18±3.5 vs. 30.89±4.21 mW/gdry, p<0.05) or 5nM (26.58±3.15 vs. 35.19±0.77 mW/gdry, p<0.05) diminished cardiac power. Conclusions: Oleate at physiological concentration masks the stimulating effects of GLP-1 and exendin-4 on myocardial glucose utilization and even causes exendin-4 to depress cardiac GU. We also suggest that oleate utilization is involved in the negative inotropic effects of both peptides.