Metabolic syndrome (MetS) represents a worldwide health problem, affecting cardiovascular and mental health. People with MetS are often suffering from depression. We used hereditary hypertriacylglycerolemic (HTG) rats as an animal model of MetS, and these were fed a high-fat-high-fructose diet (HFFD) to imitate unhealthy eating habits of people having several MetS risk factors and suffering depression. Male HTG rats were fed a standard diet (HTG-SD) or HFFD for eight weeks (HFFD8). Venlafaxine was administered for the last three weeks of the experiment (HFFD8+VE). Heart function was observed on the level of intact organisms (standard ECG in vivo), isolated hearts (perfusion according to Langendorff ex vivo), and molecular level, using the RT-PCR technique. The function of the isolated perfused heart was monitored under baseline and ischemia/reperfusion conditions. Analysis of ECG showed electrical abnormalities in vivo, such as significant QRS complex prolongation and increased heart rate. Ex vivo venlafaxine significantly reduced QT interval after ischemia/reperfusion injury. Baseline values of contractile abilities of the heart tended to be suppressed by HFFD. A significant reduction of LVDP was present in the HFFD8 group. Molecular analysis of specific genes involved in cardiac electrical (Cacna1c, Scn5a), contractile (Myh6, Myh7), metabolic function (Pgc1alpha) and calcium handling (Serca2a, Ryr2) supported some of the functional findings in vivo and ex vivo. Based on the present effect of venlafaxine on heart function, further research is needed regarding its cardiometabolic safety in the treatment of patients with MetS suffering from depression. Keywords: Metabolic syndrome, Venlafaxine, ECG, Cardiac contraction, Ischemia/Reperfusion.

• MeSH
• Diet, High-Fat * adverse effects   MeSH
• Fructose * adverse effects   administration & dosage   MeSH
• Hypertriglyceridemia * genetics   complications   drug therapy   MeSH
• Cardiovascular Diseases * etiology   prevention & control   MeSH
• Rats MeSH
• Metabolic Syndrome * drug therapy   physiopathology   MeSH
• Rats, Wistar MeSH
• Venlafaxine Hydrochloride * pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fructose * MeSH
• Venlafaxine Hydrochloride * MeSH

In in vivo cardiovascular or toxicological studies involving rat models, changes in selected electrocardiographic (ECG) parameters are monitored after various interventions to assess the origin and development of heart rhythm disorders. Each ECG parameter has diagnostic significance; as such, commonly evaluated ECG parameters, including heart rate, PR interval, P wave duration, P wave amplitude, QRS complex, QT and QTc interval duration, R wave and T wave amplitude, of rats under various types of general anesthesia were the focus of this study. Studies that performed in vivo cardiovascular or toxicological experiments in rats were retrieved from a search of the Web of Science database for articles published mainly between 2000 and 2021. In total, the search retrieved 123 articles. ECG parameters that were reported as baseline or control values were summarized and averages with ranges were calculated. It is important to be cautious when interpreting results and, in discussions addressing the mechanisms underlying a given type of arrhythmia, acknowledge that initial ECG parameters may already be affected to some extent by the general anesthesia as well as by sex and the time of day the experiments were performed.

• MeSH
• Anesthesia, General adverse effects   MeSH
• Electrocardiography * methods   MeSH
• Rats MeSH
• Heart MeSH
• Arrhythmias, Cardiac * diagnosis   MeSH
• Heart Rate physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.

• MeSH
• Biometry MeSH
• Fructose adverse effects   MeSH
• Indoles pharmacology   therapeutic use   MeSH
• Rats MeSH
• Metabolic Syndrome drug therapy   enzymology   etiology   MeSH
• Myocardium metabolism   MeSH
• NF-kappa B metabolism   MeSH
• Rats, Wistar MeSH
• Drug Evaluation, Preclinical MeSH
• Pyridines pharmacology   therapeutic use   MeSH
• Rutin pharmacology   therapeutic use   MeSH
• Heart drug effects   MeSH
• Nitric Oxide Synthase Type III metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fructose MeSH
• Indoles MeSH
• NF-kappa B MeSH
• Nos3 protein, rat MeSH Browser
• Pyridines MeSH
• Rutin MeSH
• SMe1EC2 MeSH Browser
• Nitric Oxide Synthase Type III MeSH