Frequency of Arrhythmias and Conduction and Antiarrhythmic Efficacy of Upstream Therapy in Patients with Acute Myocardial Infarction with Comorbid Metabolic Syndrome and Vascular Endothelial Dysfunction

Context. Cardiac arrhythmias and conduction disorders are the most common reperfusion complications in patients with myocardial infarction (MI) in both acute and late postinfarction periods, which significantly complicates the course of the disease and often leads to an unfavorable prognosis for the early and distant periods. Objective. To evaluate the frequency of arrhythmias and conduction and the antiarrhythmic efficacy of upstream therapy in patients with acute MI with comorbid metabolic syndrome (MS) and endothelial vascular dysfunction. Materials and methods. The experimental group consisted of 42 patients with acute myocardial infarction in combination with MS, who underwent urgent coronary angiography followed by balloon angioplasty and stenting of the infarct-dependent coronary artery, as well as standard drug therapy according to the MOH protocol. Patients in the experimental group also received 5 intravenous infusions of arginine-carnitine mixture (4.2 g and 2.0 g, respectively) in 100 ml of solvent. The nature of the clinical course of MI was compared with that in 38 patients with MI in combination with MS (control group), who did not receive additional treatment and were comparable in age (56.64 ± 0.91 and 54.85 ± 0.76 years, respectively). Results. It was found that patients with MI with comorbid MS on percutaneous coronary intervention most often developed reperfusion syndrome with manifestations of arrhythmias and conduction. Under the influence of standard drug treatment in patients of the control group there was a significant clinical and functional improvement, though sinus tachycardia, ventricular extrasystole of high grades and supraventricular extrasystole remained resistant to treatment. There was also a pronounced endothelial vascular dysfunction, which in the process of standard treatment in patients of the control group did not reach the level of healthy individuals (p-value less than 0.05). Conclusions. In patients with acute MI with comorbid MS, who underwent balloon angioplasty and stenting of the infarct-dependent coronary artery, a pronounced vascular endothelial dysfunction and electrical instability is observed, accompanied by reperfusion arrhythmias and arrhythmias. The use of arginine-carnitine mixture as upstream therapy helped to restore endothelial function and showed a pronounced antiarrhythmic effect, which significantly reduced the incidence and severity of complications of acute MI such as reperfusion arrhythmias.

Abstract 286: Role of ATP-sensitive Potassium Channel Openers in Prevention of Atrial Fibrillation

Introduction: The ATP-sensitive potassium (K ATP ) channel dysfunction causes susceptibility to adrenergic atrial fibrillation (AF). However, the therapeutic efficacy of K ATP activation in primary prevention of AF is not known. We hypothesized that K ATP channel opening drugs prevent AF with effective metabolic and mechanosensitive gating of K ATP channels and preserving electro-anatomical stability in atria by regulating oxidative and metabolic states. Methods: This hypothesis was tested in a novel mouse model of AF, cardiac specific LKB1 knockout (KO) mice. Male and female LKB1 KO mice were treated with K ATP channel openers, nicorandil (15 mg/kg/day) and diazoxide (10 mg/kg/day). Control group included untreated littermates of the study group. Incidence of AF, structural and electrophysiological property of atria and sex-based differences were analyzed at the 3 months of age in all groups. Results: The incidence of spontaneous AF was significant reduced in LKB1 KO male mice with nicorandil (0%, n=5) and diazoxide (33%, n=6) treatment compare to untreated mice (84.6%, n=13) (p<0.05). The treatment was also effective in female LKB1 KO mice as AF occurred in 37.5% of nicorandil (n=8) and 40% of diazoxide (n=5) (p<0.05) treated mice as oppose to 71% of untreated mice (n=24). The K ATP openers, particularly nicorandil, were more effective in male mice preventing AF. There was 100% risk reduction with nicorandil in male mice compare to 39% with diazoxide. Nicorandil demonstrated 52% risk reduction in female mice while it was 56% with diazoxide treatment. Prevention of AF was associated with preservation of atrial structural and electrical property including size, heart rate and conduction intervals. Biatrial enlargement was significantly prevented by K ATP openers compare to untreated mice. Incidence of AF was significantly higher in male mice than female with or without treatment. Conclusions: Activation of sarcolemmal and mitochondrial K ATP channels prevents AF by preserving electro-anatomical property of atria and decreasing susceptibility to AF. Metabolic regulation of K ATP is essential in AF. Thus, the K ATP openers are novel upstream therapy for primary prevention of AF in vulnerable population.