Anti-arrhythmic and cardio-protective effects of atorvastatin and a potent pyridoindole derivative on isolated hearts from rats with metabolic syndrome

Abstract

OBJECTIVES: Aims of this study were to investigate the anti-arrhythmic and cardio-protective effect of atorvastatin and of a new pyridoindole derivative (SMe1EC2) on isolated and perfused hearts while following the Langendorff principles. BACKGROUND: Metabolic syndrome is a widely distributed condition progressing to cardiovascular disease. Many of the metabolic syndrome patients take (HMG)-co-enzyme A (CoA) reductase inhibitors with potential cardioprotective effects. SMe1EC2 is a promising new drug, exerting many positive effects in experimental settings. METHODS: Rats with induced metabolic syndrome were treated with atorvastatin (25 mg/kg) and SMe1EC2 (25 mg/kg and 0.5 mg/kg, respectively) daily for 3 weeks. After the treatment, the hearts were isolated and perfused according to Langendorff. RESULTS: Both atorvastatin and SMe1EC2 improved cardiac function by elevating the left ventricular developed pressure (VLDP) and cardiac contractility. Both SMe1EC2-treated groups improved LVDP during reperfusion, signifi cantly increased-dP/dt, and moderately elevated +dP/dt values. The treatment with both atorvastatin and SMe1EC2 (25 mg/kg) signifi cantly reduced malignant arrhythmia in comparison to control group and group treated with SMe1EC2 0.5 mg/kg. CONCLUSIONS: Owing to its anti-arrhythmic and cardio-protective effects, atorvastatin and SMe1EC2 could be of benefi t to patients suffering from metabolic syndrome (Tab.

Mechanisms Underlying Antiarrhythmic Properties of Cardioprotective Agents Impacting Inflammation and Oxidative Stress

“…In addition, spontaneous VF during ischemia-reperfusion was suppressed by rosuvastatin [193]. Moreover, the following atorvastatin effects have also been noted; (1) atorvastatin protected the rat myocardium from ischemia-reperfusion induced arrhythmias [194,195]; (2) it ameliorated rat cardiac sympathetic nerve remodeling and prevented VT/VF following myocardial infarction, and it down-regulated IL-1β and TNF-α expression [196]; (3) its antiarrythmia effects may also be due to IL-1β and IL-6 suppression in ouabain-induced rat arrhythmias [197] and (4) it reduced elevated hs-CRP, IL-6 and TNF-α which correlate with longer effective refractory period in the sterile-goat pericarditis model [198]. In contrast, non-treated peri carditis animals had a longer AF duration than the treated group.…”

Effect of selected cardiovascular factors on mortality in patients with ST-segment elevation myocardial infarction treated with primary coronary intervention

“…Among the factors, many of them increase the risk of the atherosclerotic disease per se. Out of lipid spectrum disorders, LDL (low-density lipoprotein) cholesterol has been specifi cally identifi ed as a factor contributing to the atherosclerosis development, while statin treatment aimed U n c o r r e c t e d at reducing the level of LDL-cholesterol contributes to the reduction in the risk of cardiovascular events (3)(4)(5)(6)(7).…”

The acidophilic microalga Coccomyxa onubensis and atorvastatin equally improve antihyperglycemic and antihyperlipidemic protective effects on rats fed on high-fat diets

“…Moreover, it is defined by its susceptibility to other comorbid conditions such as cognitive deficits, nonalcoholic fatty liver, and some forms of cancers (Grundy et al 2004;Saklagen 2018). Diabetes is a metabolic disease which when complicated with hypertension increases the risk of cardiovascular (CV) diseases (Liptak et al 2019). Statins have been broadly used as an antihypercholesterolemic drug in animals and humans because they inhibit the HMG-CoA reductase activity, and consequently the biosynthesis of cholesterol in the liver (Chen et al 2011).…”