Potential Cardioprotective Effects of Orlistat for Treatment of Myocardial
Francisco Sandro Menezes-Rodrigues1, José Gustavo Padrão Tavares1, Erisvaldo Amarante de Araújo1, Luciana de Paula2, Paolo Ruggero Errante1, Afonso
Caricati-Neto1 and Leandro Bueno Bergantin1*
1Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil
2Laborvisa–Laboratório de Análises Clínicas, São Paulo-SP, Brazil
*Corresponding author: Leandro Bueno Bergantin, Ph.D. Laboratory of Autonomic and Cardiovascular Pharmacology, Department of Pharmacology-Escola Paulista de
Medicina (EPM), Universida Federal de São Paulo (UNIFESP), Brazil, Tel: 55 11 5576-4973; E-mail: email@example.com
Received date: July 13, 2017; Accepted date: July 21, 2017; Published date: July 28, 2017
Copyright: © 2017 Bergantin LB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute myocardial infarction (AMI) is characterized by ischemic
lesions that severely compromise cardiac structure and function, and
even the survival of mammals. e ischemic cardiac diseases (ICD) are
related to million deaths per year in the world [1,2]. Although
convencional therapy is based on the cardiac reperfusion (R), this
procedure increases cardiac damage caused by ischemia (I), and severe
arrhythmias (e.g. ventricular arrhythmias and atrio-ventricular
blockade) [2-5]. Several reports have demonstrated that cardiac
arrhythmias caused by myocardial ischemia and reperfusion (I/R)
could be originated from bioenergetic, and electrochemical, imbalance
triggered mainly by decrease of ATP synthesis by mitochondria, and
cytosolic Ca2+ overload in cardiomyocytes [2-5]. is Ca2+ overload is
massively worsed by the increase of Ca2+ inux through L-type
voltage-activated Ca2+ channels (VACC) caused by continuous
membrane depolarization of cardiomyocytes during cardiac I/R [2-5].
In addition, cytosolic Ca2+ overload promotes accumulated Ca2+ in the
mitochondrial matrix via increase of Ca2+ inux through
mitochondrial uniporter, leading to mitochondrial bioenergetic
collapse, and excessive production of free radical, which compromises
the structure and function of mitochondria, and other cytoplasmic
organelles [2-5]. ese cellular mechanisms importantly contribute for
developing arrhythmias, and death in AMI patients. Despite
continuous advances in AMI treatment, a high ratio of patients dies
suddenly in the early hours before arriving at the hospital [6-9]. Most
of these early deaths are due to complex ventricular arrhythmias (VA)
and atrio-ventricular blockade (AVB) [6-9]. Surprisingly, there is still
lack of knowledge about the exact events of these early malignant
arrhythmias, and their cellular and molecular mechanisms. Due to
involvement of intracellular Ca2+ overload in cardiac arrhythmias
caused by myocardial I/R, the use of pharmaceuticals that reduce this
Ca2+ overload represents an alternative pharmacological approach to
the treatment of ischemic cardiac diseases in humans, including AMI.
Nonetheless, the cardiac reperfusion (R) continues to be the therapy
more used to treat ICD [6-9]. Among the various risk factors for
persuing cardiac I/R, we can highlight obesity; this disease has
worldwide importance, and it is intrinsically related to cardiovascular
diseases (e.g. atherosclerosis and thrombosis). erefore, there is an
incessant and required worldwide research for drugs that eectively act
in the treatment of obesity. is is a metabolic disease that arises from
biochemical, hormonal and energetic disorders [10,11]. Several drugs
are used for the pharmacotherapy of obesity-FDA approved
pharmacological monotherapy options-including orlistat (ORL,
pancreatic lipase inhibitor) [12,13]. erefore, our group decided to
evaluate potential cardioprotective eects of the agents used in the
pharmacotherapy (such as ORL) of dyslipidemia in normotensive rats-
treated with ORL for ten days-and submitted to the model of in vivo
cardiac I/R developed by our group . e cardioprotection was
analyzed by evaluation of the electrophysiological parameters through
the electrocardiogram analysis (arrhythmias), and serum
concentration biochemical markers of cardiac lesion produced in
response to the cardiac I/R protocol (creatine kinase (CK)), low-
density lipoprotein cholesterol (LDL-C) and lethality. We observed that
the treatment with ORL could decrease the lethality, the serum levels
of CK and LDL-C compared to control groups, indicating
cardioprotective eects of the ORL. ese results suggest that ORL
produced cardioprotective eects against cardiac damage caused by
Research supported by CNPq, FAPESP and CAPES.
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Citation: Menezes-Rodrigues FS, Padrão Tavares JG, Araújo EA, Paula LD, Errante PR, et al. (2017) Potential Cardioprotective Effects of
Orlistat for Treatment of Myocardial Infarction. J Thrombo Cir 3: e108. doi:10.4172/2572-9462.1000e108
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