Suppression of Ventricular Arrhythmias After Myocardial Infarction by AT1 Receptor Blockade: Role of the AT2 Receptor and Casein Kinase 2/Kir2.1 Pathway

Excerpt

Ventricular arrhythmias (VAs) after myocardial infarction (MI) have been a source of concern for decades because they contribute to mortality in the post-MI survivors. Common VAs, spontaneous or programmed electrical stimulation (PES) induced, include premature ventricular depolarizations or complexes (PVCs), couplets, triplets, non-sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) or VT/VF. Without doubt, major advances have been made in therapy for their control and prevention, with the development of pharmacologic and electrophysiological approaches including antiarrhythmic agents, beta-adrenergic drugs, catheter ablation, and the implantable cardioverter-defibrillator (ICD). In parallel, an added benefit of renin-angiotensin-aldosterone system (RAAS) blockers introduced for therapy of post-MI left ventricular (LV) remodeling and dysfunction, including the angiotensin II (AngII) type 1 receptor (AT₁R) antagonists or blockers (ARBs), has been the suppression of VAs and sudden cardiac deaths (SCDs) as well as “final” deaths and their contribution to improved survival and outcome [1‐7]. However, the precise molecular mechanism for the ARB-induced suppression of VAs has been elusive. A major goal of translational research has therefore been to not only unravel the underlying molecular mechanisms for post-MI VAs in general, but also to identify the precise molecular mechanisms and novel pathways resulting in their suppression so that they may be specifically targeted. There is a definite need for new therapies because a significant percentage of post-MI survivors continue to develop VAs resulting in SCD or “final” death despite optimal therapy including reperfusion [4, 7]. …