The effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet

Abstract

Metabolic syndrome represents one of the major health, social and economic issues nowadays, and affects more than 25% people worldwide. Being a multifactorial health problem, metabolic syndrome clusters various features, such as obesity, dyslipidemia, hyperglycemia and hypertension. Each of these disturbances represents a risk factor for developing cardiovascular disease. Moreover, patients with metabolic syndrome are more likely to suffer from depression, thus treatment with antidepressants (e.g. venlafaxine) is often neccessary. However, many of the antidepressants themselves may contribute to worsening or even development of the metabolic syndrome, thus creating a “vicious circle”. The aim of this work was to investigate on the animal model of metabolic syndrome, i.e. on hypertriacylglycerolemic rats fed high-fat-fructose diet (HFFD): 1) the effect of a change in diet from HFFD to a standard diet (SD) and the effect of venlafaxine treatment, 2) during HFFD, 3) as well as during a changed diet to SD. We focused on biometric parameters, blood pressure and selected ECG parameters. We observed the reversibility of the present metabolic and cardiovascular changes by switching the HFFD to SD in the last 3 weeks of the experiment. Switch to the standard diet led to decrease of body weight, even in the presence of venlafaxine. Administration of venlafaxine caused the decrease of heart weight/body weight index in rats fed with HFFD compared to the untreated group fed with HFFD for 8 weeks. Blood pressure, which was increased in the HFFD group showed a tendency to decrease to control values after switching to the standard diet. Administration of venlafaxine led to significant increase in all parameters of blood pressure when rats were fed with HFFD throughout the whole experiment. In untreated rats fed with HFFD for 8 weeks, we observed a shorter PQ interval and prolonged QRS complex as well as QTc interval compared to untreated rats with diet switched to SD. This effect was potentiated by venlafaxine administered not only during HFFD but even after switch to SD. Our results point to the fact that metabolic syndrome is clearly affecting the function of the cardiovascular system by modifying blood pressure and electrical activity of the heart. Moreover, administration of venlafaxine may lead to worsening of the observed changes, especially in the presence of high-fat-fructose diet.

The Risk of Fatal Arrhythmias in Post-Myocardial Infarction Depression in Association With Venlafaxine

“…At therapeutic levels, venlafaxine has a thirty times higher affinity for serotonin receptors than noradrenaline receptors [20]. Venlafaxine may cause mild tachycardia, headache, dry mouth, increased HR and BP, decreased HRV, QTc prolongation, and TdP at higher doses by blockage of cardiac sodium channels, it acts like an SSRI at lower doses but is more efficacious at higher doses, so when it is prescribed in treatment-resistant depression, PTSD, generalized anxiety disorders (GAD), panic disorders close monitoring is advised to prevent adverse cardiac events like tachyarrhythmias, hypertensive crisis, angina, extra-systoles, CHF and SCD [2,6,[8][9][10]15,16,[20][21][22]. Inhibition of cardiac and vascular Ca2+, K+, and Na+ channels by SSRIs and SNRIs may be associated with cardiac adverse events in susceptible patients [23].…”

“…Metabolic syndrome (MetS) affects a quarter of the world population, and 60% of patients with psychiatric disorders die from causes like CVD which are co-morbid with MetS, depression has a bidirectional relationship with MetS and obesity [ 20 ]. MetS increases the risk of QTc prolongation [ 20 ].…”

“…Metabolic syndrome (MetS) affects a quarter of the world population, and 60% of patients with psychiatric disorders die from causes like CVD which are co-morbid with MetS, depression has a bidirectional relationship with MetS and obesity [ 20 ]. MetS increases the risk of QTc prolongation [ 20 ]. In animal studies venlafaxine increased the risk for central obesity, MetS, lowered ventricular fibrillation (VF) threshold, and shortened restoration time of sinus rhythm in combination with a high-fat-fructose diet; it also blocked fast inward sodium currents in ventricular myocytes leading to QRS prolongation [ 20 ].…”

“…MetS increases the risk of QTc prolongation [ 20 ]. In animal studies venlafaxine increased the risk for central obesity, MetS, lowered ventricular fibrillation (VF) threshold, and shortened restoration time of sinus rhythm in combination with a high-fat-fructose diet; it also blocked fast inward sodium currents in ventricular myocytes leading to QRS prolongation [ 20 ].…”

Statins and Antidepressants: A Comprehensive Review and Clinical Outlook of the Risks and Benefits of Co-prescription (2022)

“…Furthermore, it is important to remember that metabolic syndrome (MetS) affects almost 25% of the population worldwide, and 60%-65% of the patients with mental health disorders die from causes linked to CVD, which are frequently comorbid with MetS [ 10 ].…”