Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts.

Olanzapine-mediated cardiotoxicity is associated with altered energy metabolism in isolated rat hearts. Acta Biochim Pol. 2020 Jan 30;: Authors: Gulac P, Arnold M, Grman M, Carrel T, Longnus S, Stankovicova T, Tomasova L Abstract Olanzapine is an antipsychotic drug routinely used for the treatment of schizophrenia. Although the olanzapine treatment is associated with disturbed electrical heart activity, the exact mechanism underlying this severe adverse effect remains unclear. Recently, olanzapine administration was demonstrated to be associated with elevation of blood glucose and lower levels of free fatty acids. Therefore, we investigated the effect of acute olanzapine administration on pathways regulating the cardiac energy metabolism in an isolated heart. Electrical activity and contractile parameters were recorded in isolated, spontaneously beating, adult male rat hearts, perfused with either olanzapine (100 nmol/l) or the vehicle for 10 min. Regulation of key signalling molecules was evaluated by immunoblotting and ATP levels were measured spectrophotometrically. Olanzapine prolonged the QTc intervals and induced a higher number of premature ventricular beats. Furthermore, olanzapine significantly decreased the coronary flow, the rate-pressure product and the contractility (+dP/dt and -dP/dt). These changes were associated with an increased acetyl-CoA carboxylase phosphorylation and tissue ATP levels. We also found a trend for ...
Source: Acta Biochim Pol - Category: Biochemistry Authors: Tags: Acta Biochim Pol Source Type: research