aliskiren and Arrhythmias--Cardiac

BACKGROUND Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. MATERIAL AND METHODS Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). RESULTS Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. CONCLUSIONS Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats.

Topics: Amides; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Captopril; Creatine Kinase, MB Form; Fumarates; Heart; Heart Rate; Male; Myocardial Reperfusion Injury; Oxidative Stress; Rats

Topics: Amides; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Fumarates; Humans; Pulmonary Veins

We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180+/-3 mm Hg) compared with dTGRs (208+/-5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110+/-3 and 119+/-6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT(c) intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.

Topics: Amides; Angiotensinogen; Animals; Animals, Genetically Modified; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Cardiac Pacing, Artificial; Cardiomegaly; Connexin 43; Dietary Fats; Disease Models, Animal; Electrocardiography; Electrophysiology; Fatty Acids, Omega-3; Fumarates; Humans; Hypertension; Magnetocardiography; Male; Rats; Rats, Sprague-Dawley; Renin; Up-Regulation