TNF- inhibition alleviates the functional post-infarction recovery of the heart

Objective: To evaluate, in vitro, the cardiac functional effects of TNF-α antagonist administration in rats after myocardial infarction.

Methods: Myocardial infarction was reproduced using a proven model based on isoproterenol i/p administra-tion in rats in 2 consecutive days in a similar dose, 150 mg/kg. In another group the animals after isoprotere-nol induced myocardial infarction (series IMI) have received daily TNF-α antagonist, a specific monoclonal antibody (ma-TNF-α) i/p in dose of 50 mg/kg during days (series IMI+ma-TNF-α). In both series the ani-mals were sacrificed after 10 days from the 1st injecti-on and their isolated hearts ware perfused with Krebs solution according to Langendorff and Neely-Rovetto models. Rats of control series administered physiologic solution.

Results: The most remarkable and statistical authentic changes of left ventricle dysfunction in 10 days after IMI in comparison to control were following: (1) diminuti-on of cardiac output (CO), systolic pressure (SP) and +dP/dT max by respectively 28.7 and 34.7 and 23.3%;

(2) negative inotropic effect to action of endothelin-1 (ET-1) manifested by decrease of SP during stimulation by 13.9%; (3) increasing by 83.3% of end diastolic pre-ssure (EDP) in maximal volume loading effort: 17.6 ± 1.66 vs. 9.6 ± 0.85 mm Hg. The ma-TNF-α administra-tion in post-infarction period led to noticeable bene-fits such as: (1) significant enhancement of SP and CO respectively by 17.3 and 18.6%; (2) appearance of the positive inotropic effect developing to ET-1 action and (3) a more than double reduction of EDP difference: 13.8 ± 1.26 vs. 9.6 ± 0.85 mm Hg (+44%).

Conclusions: T he beneficial effect of AM-TNF-α on functional recovery of heart in experimental myocardi-al infarction clearly indicates the role of inflammation in post-infarction remodeling of the myocardium and justifies inflammation as a target of forecast prediction and therapy as well.

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)