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Objectives: Considering the recent discovery of postconditioning, we investigated whether intermittent dyssynchrony immediately upon reperfusion induces cardioprotection as well., Background: Intermittent dyssynchrony, induced by ventricular pacing, preconditions myocardium., Methods: Isolated ejecting rabbit hearts were subjected to 30-min coronary occlusion and 2-h reperfusion. Control, left ventricular (LV) pacing preconditioning (LVPpreC) (3 x 5-min LV pacing), and LV pacing postconditioning (LVPpostC) (10 x 30-s LV pacing during early reperfusion) groups were studied. Mechanical effects of LV pacing were determined using local pressure-length loops (sonomicrometry), whereas effects on myocardial lactate release and coronary flow were assessed from coronary effluent and fluorescent microspheres, respectively. Anesthetized pigs underwent 60-min coronary occlusion and 3-h reperfusion in control and right ventricular (RV) pacing postconditioning groups (RVPpostC) (10 x 30-s RV pacing during early reperfusion). In all hearts, area at risk and infarct size were determined with blue dye and triphenyltetrazolium chloride staining, respectively., Results: Infarct size, normalized to area at risk, was 47.0 +/- 12.3% in control rabbit hearts, but significantly smaller in LVPpreC (17.8 +/- 6.4%) and LVPpostC hearts (17.9 +/- 4.4%). Left ventricular pacing significantly altered regional mechanical work, but did not affect coronary flow or lactate release. In pigs, infarct size was significantly smaller in RVPpostC (9.8 +/- 3.0%) than in control (20.6 +/- 2.2%) animals., Conclusions: Intermittent dyssynchrony during early reperfusion reduces infarct size in 2 different animal models. Dyssynchrony-induced postconditioning cannot be attributed to graded reperfusion but may be induced by modulation of local myocardial workload. Dyssynchrony-induced postconditioning opens new possibilities for cardioprotection in the clinical setting.

Introduction: Line stimulation across fibers generates a virtual electrode (VE) pattern that consists of adjacent +Vm and -Vm regions. In this study, we evaluated Vm at the break of line stimulation pulses to determine where arrhythmias arise and their propagation direction relative to +Vm and -Vm regions., Methods and Results: We optically mapped the anterior left ventricular epicardium of isolated rabbit hearts (n = 9). Monophasic line stimuli were applied across fibers at various coupling intervals. In 18 of 24 break arrhythmias, i.e., arrhythmias in which propagation occurred after the break but < or = 30 msec postshock, excitation propagated from the border between +Vm and -Vm regions toward the -Vm region (P < 0.05) for either shock polarity, even though locations of positive and negative Vm changed with shock polarity. In 13 of 18 make arrhythmias, i.e., arrhythmias in which propagation occurred before the break, the excitation propagated from the center of the +Vm region toward the -Vm regions (P < 0.05). For late arrhythmias, i.e., arrhythmias in which propagation was found >30 msec postshock, propagation was reversed, i.e., toward the +Vm region (P < 0.01), which was where the positive VE produced action potential prolongation., Conclusion: The propagation of break, make, and late arrhythmias is spatially related to VEs. The different direction of propagation of late arrhythmias relative to the VEs is explained by the delayed recovery of Vm due to VE-induced action potential prolongation.

Intracellular calcium concentration and transmembrane potentials are two important measurements used to study the mechanisms of cardiac activity. Fluorescent dyes have been used to measure these separately but not simultaneously in cardiac tissue. Fluo-3 and Fluo-4 (a recently improved version of Fluo-3) have been used to measure changes in intracellular calcium concentration and Di-4 ANEPPS has been used to measure transmembrane potentials. This paper addresses the feasibility of using these fluorescent dyes together in order to measure transmembrane potentials and intracellular calcium concentration simultaneously. For the dyes to be used simultaneously, their respective fluorescence spectra must be sufficiently separated in wavelength in order to allow them to be separated by optical filters or spectrographs. An apparatus was constructed to measure the dyes' spectra in a fluorescence imaging chamber as well as in an isolated perfused rabbit heart. The measured spectra were mathematically modeled in order to assess the spectral overlap error under different conditions. Error graphs were constructed which may help researchers select optical filters and dye concentrations that will result in an acceptable error.

This study evaluated effective resistances on the ventricular surfaces of arterially-perfused rabbit hearts. Effective resistances were determined with a four-electrode array that was parallel or perpendicular to epicardial fibers. Resistance along or across epicardial fibers was determined by applying current to the epicardium with two parallel line electrodes and measuring potentials in the region between the electrodes. Computer simulations were performed to gain insight into the distribution of current in the ventricular wall. The effective resistances were not different along versus across fibers. Simulations showed that transmural rotation of fibers causes current to be distributed differently when the electrode is oriented perpendicular versus parallel to epicardial fibers. When the array is oriented so that epicardial current is across fibers, the fraction of current that flows transmurally and along the deeper fibers increases while the fraction of current that flows epicardially decreases. This introduces isotropy of the effective resistance. Thus, in contrast to isolated cardiac fibers, the ventricular epicardium exhibits isotropic effective resistance due to transmural rotation of fibers. The rotation and isotropic resistance may be important for cardiac electrical behavior and effects of electrical current in the ventricles.

The sign of transmembrane voltage (Vm) change (delta Vm) in the heart during unipolar point stimulation is nonuniform, which introduces dispersion of states of Vm-dependent ion channels that depends on fiber orientation. We hypothesized that line stimulation parallel to cardiac fibers increases regional uniformity of the delta Vm sign. To test this, we evaluated electrode current distribution and delta Vm produced by unipolar line stimulation in isolated rabbit hearts. The Vm-sensitive fluorescent dye, di-4-ANEPPS, and a laser scanner provided delta Vm measurements at 63 spots in an 8 x 8-mm epicardial region. Line stimulation was tested at specific angles with respect to the fiber direction. Current peaks occurred at electrode ends. For electrodes parallel to fibers (0 degree), epicardium in regions beyond the ends exhibited a nonuniform delta Vm sign, whereas epicardium between the ends exhibited a uniform delta Vm sign that was essentially negative (hyperpolarized) during anodal pulses and positive (depolarized) during cathodal pulses. The delta Vm sign between the ends became less uniform when the stimulation angle was increased relative to the long axis of the fibers. At 90 degrees, the delta Vm sign between the ends was nonuniform and was frequently opposite, near versus away from the electrode. Spatial distributions of delta Vm during line stimulation were qualitatively predictable from anisotropic effects of point stimulation provided that combined effects of points along the electrode and points with higher current near ends were considered. For biphasic line stimulation, delta Vm during the second phase was weakly correlated with the temporal sum of effects of phases given individually, indicating limited ability of summation to predict delta Vm. Thus, uniformity of the delta Vm sign during stimulation is enhanced in the region between the ends of a line electrode parallel to fibers. This may lessen arrhythmogenic dispersion of Vm-dependent ion channel states in the region.