The asynchronous ventricular activation during LBBB leads to redistribution of circumferential shortening and myocardial blood flow and, in the long run, LV remodelling. Septal hypoperfusion during LBBB appears to be primarily determined by reduced septal workload.

The main goal of this article was to review animal experimental work on the effect of asynchronous activation on ventricular pump function. During normal sinus rhythm and atrial pacing, the Purkinje system contributes significantly to the rapid electrical activation of the ventricles. In contrast, during ventricular pacing the impulse is almost exclusively conducted through the normal myocardium. As a consequence, electrical activation of the ventricles becomes asynchronous and has an abnormal sequence. The abnormal impulse conduction causes considerable disturbances to occur in regional systolic fiber shortening, mechanical work, blood flow, and oxygen consumption; low values occurring in early activated regions and values above normal being present in late activated regions. Many animal studies have now shown that the abnormal electrical activation, induced by ventricular pacing, leads to a depression of systolic and diastolic LV function. Pacing at the right ventricular apex (the conventional pacing site) reduces LV function more than pacing at the high ventricular septum or at LV sites. In canine hearts with experimental LBBB, LV pacing significantly improves LV pump function. Differences in LV pump function between (combinations of) pacing sites are poorly correlated with QRS duration. Therefore, the cause of the depression of LV function during abnormal electrical activation appears to be a combination of the asynchrony and the sequence of activation. These experimental findings justify continuing attention for optimizing the site(s) of ventricular pacing in patients with normal and abnormal ventricular impulse conduction.

During ventricular pacing, LV pump function is maintained best (i.e., at SR level) when pacing at the LV septum or LV apex, potentially because pacing from these sites creates a physiological propagation of electrical conduction.

In LBBB hearts, optimal restoration of LV systolic function by pacing requires intra-ventricular resynchronization. The optimal AV delay to achieve this depends on both the site of pacing and baseline PQ time.

PA-6 has higher efficiency and specificity to KIR2.x-mediated current than P, lengthens action potential duration, and does not affect channel trafficking at concentrations relevant for complete IK₁ block.