Discrepant effects of heart failure on electrophysiological property in right ventricular outflow tract and left ventricular outflow tract cardiomyocytes

Ventricular arrhythmias commonly arise from the right (RVOT) and left ventricular outflow tracts (LVOT) in patients without structural heart disease. Heart failure (HF) significantly increases the risk of ventricular arrhythmias. The regional differences and how HF affects the electrophysiological characteristics of RVOT and LVOT cardiomyocytes remain unclear. The whole-cell patch-clamp technique was used to investigate the action potentials and ionic currents in isolated single RVOT and LVOT cardiomyocytes from control rabbits and rabbits with HF induced by rapid ventricular pacing. Comparison with control LVOT cardiomyocytes showed that control RVOT cardiomyocytes have a shorter action potential duration (APD), smaller late Na⁺ currents (I_Na-late), larger transient outward (I_to) and larger delayed rectifier K⁺ currents (I_Kr-tail), but had similar L-type Ca²⁺ currents (I_Ca-L) and Na⁺/Ca²⁺ exchanger (NCX) current. HF increased APD, I_Na-late and NCX, but decreased I_Ca-L and I_to in RVOT cardiomyocytes. In contrast with this, HF decreased APD and I_Ca-L, but increased I_to and I_Kr-tail in LVOT cardiomyocytes. In conclusion, RVOT and LVOT cardiomyocytes had distinctive electrophysiological characteristics. HF differentially modulates action potential morphology and ionic currents in RVOT and LVOT cardiomyocytes.