The influence of body weight and oxidative stress in heart failure with preserved ejection fraction, experimental model

Introduction: Heart failure with preserved ejection fraction (HFpEF) represents a complex and heteroge-neous clinical syndrome, which is increasingly preva-lent and associated with poor outcomes. The HFpEF treatment options are limited and mostly based on the treatment and relief of the comorbidities and the use of diuretics. One of the non-cardiac important co-morbidities associated with HFpEF is obesity. Obesity through the associated subclinical inflammatory state, vascular endothelial dysfunction and systemic oxidati-ve stress may influence systolic and/or diastolic heart function.

Objective: In this context the aim of our study was 1) to explore the relationship between obesity and heart function in a heart failure rat model and 2) to assess the efficacy of an antioxidant treatment with alpha-lipoic acid.

Methods: Six weeks old Sprague-Dawley rats were either included in the Control group (n=6) or sub-jected to abdominal aortic banding (AAB) and sub-sequently divided into 3 groups: rats fed with stan-dard diet (AAB+standard diet) (n=8), hypercaloric diet (AAB+DIO) (n=9) and rats fed with hypercalo-ric diet and additionally treated with alpha lipoic acid (AAB+DIO+AL) (n=9). Alpha lipoic acid (AL) was administered intraperitoneal discontinuously daily for two weeks every month. Over a 28-week period, rats were monitored by measurements of body wei-ght (BW), systolic blood pressure (SBP) and echocar-diographic parameters. General oxidative status was evaluated by measurement of plasma hydroperoxides levels (FORT test).

Results: Starting with the 8th week, the hypercaloric diet induced a significant (p<0.05) increase in rats’ BW with ~11.5% over the Control group. The weight gain was associated with a significant increase (p<0.05) in SBP and plasma hydroperoxides. Regarding heart function, we noted a significant decrease in early-to-late fi-ling ratio (E/A) in the AAB rats fed with hypercaloric diet since week 20 (p<0.05) while for AAB rats fed with standard diet this reduction in E/A ratio is less intense and occurs only at 28 weeks (p<0.05). After 28 weeks of study the ejection fraction was reduced with ~12% in both legated groups regardless of type of diet. The discontinuous treatment with AL reduced the rats’ BW fed with DIO with 7-10% (p<0.05) and improved SBP and plasma hydroperoxides levels as early as week 8. In this context, in the rats fed with hypercaloric diet and treated concomitantly with AL, the E/A ratio decreases only after 28 weeks (p<0.05).

Conclusions: In our experimental conditions abdomi-nal aorta banding was associated with an alteration of diastolic function after 28 weeks, process that occurred earlier on the background of BW gain. The discontinu-ous treatment with alpha-lipoic acid associated to the hypercaloric diet was able to reduce the rats’ BW, SBP and plasma hydroperoxides and to delay the onset of diastolic dysfunction. These promising results could open new perspectives for the use of alpha-lipoic acid in cardiometabolic disorders.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)