Abstract
IntroductionThe upstroke of optical action potentials (APs) recorded from intact hearts are generally recognized to be slower than those recorded with microelectrodes. This is thought to reflect spatial signal averaging within the volume of tissue that makes up the optical signal. However, to date, there has been no direct experimental study on the relationship between conduction velocity (CV) and optical AP upstroke morphology in the intact heart. Notably, it is known that sodium channel block and gap junction inhibition, which both slow CV, exert differential effects on the upstroke velocity of microelectrode-recorded APs. Whether such differences are evident in optical APs is not known. The present study sought to determine the relationship between tissue CV and optical AP upstroke velocity in intact mouse hearts.Materials and MethodsIsolated, perfused mouse hearts were stained with the potentiometric dye Rh-237. Fluorescent signals were recorded from across the anterior surface of the left and right ventricles during constant pacing. Maximum rate of change in fluorescence (dF/dtmax) and tissue CV were assessed in control conditions, during an acute period of low-flow ischemia, and following perfusion of flecainide (1–3 μmol/L), a sodium channel blocker, or carbenoxolone (10–50 μmol/L), a gap junction inhibitor.ResultsDuring epicardial pacing, an anisotropic pattern was observed in both activation and dF/dtmax maps, with more rapid optical AP upstroke velocities orientated along the fastest conduction paths (and vice versa). Low-flow ischemia resulted in a time-dependent slowing of ventricular CV, which was accompanied by a concomitant reduction in optical AP upstroke velocity. All values returned to baseline on tissue reperfusion. Both flecainide and carbenoxolone were associated with a concentration-dependent reduction in CV and decrease in optical AP upstroke velocity, despite distinct mechanisms of action. Similar responses to carbenoxolone were observed for low- (156 μm pixel with) and high- (20 μm pixel width) magnification recordings. Comparison of data from all interventions revealed a linear relationship between CV and upstroke dF/dt.ConclusionIn intact mouse hearts, slowing of optical AP upstroke velocity is directly proportional to the change in CV associated with low-flow ischemia, sodium channel block, and gap junction inhibition.
Highlights
The upstroke of optical action potentials (APs) recorded from intact hearts are generally recognized to be slower than those recorded with microelectrodes
Computational modeling studies suggest that the rise time of optical AP in simulated human ventricle is a nonlinear function of tissue conduction velocity (CV); where slower CV equates to an increase in the time for tissue activation and a slower AP upstroke (Hyatt et al, 2003)
VF∗ is the fractional amplitude at which the optical AP upstroke has its fastest rate of rise and is shown in previous studies to reflect the subsurface orientation of depolarizing wavefronts as they spread through the myocardium (Hyatt et al, 2003, 2005, 2008; Zemlin et al, 2008)
Summary
The upstroke of optical action potentials (APs) recorded from intact hearts are generally recognized to be slower than those recorded with microelectrodes. The morphology of action potentials (APs) recorded with optical mapping typically exhibit reduced upstroke velocity and longer rise times compared to those recorded from the same tissues with microelectrode techniques (Morad and Salama, 1979; Girouard et al, 1996; Hyatt et al, 2003; Salama et al, 2005; Bishop et al, 2007) (though not all studies agree) (Windisch et al, 1985). There has, been no experimental examination of the impact of conduction slowing on optical AP upstroke morphology in intact hearts
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