A single electrical pulse within the protective zone of each cardiac cycle prevented reperfusion-induced ventricular tachycardia in conscious mice

Figures

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  Figure 1. Presents a schematic representation of a mouse chronically instrumented with a PA‐C10 transmitter, left ventricular‐stimulating electrodes, coronary artery occluder, positive (pos) and negative (neg) electrocardiogram electrodes, and a ground (G) electrode.

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  Figure 2. Presents an original recording of one electrocardiogram complex. Note that in the mouse the ST segment is not isoelectric and has a characteristic J‐wave that represents early repolarization (Boukens et al. 2013). The vulnerable zone was a period within the cardiac cycle during which a precisely timed single electrical impulse caused ventricular tachycardia. The protective zone was a period within the cardiac cycle during which a precisely timed stimulus blocked the induction of ventricular tachycardia caused by an earlier stimulus within the vulnerable zone.

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  Figure 3. Panel (A) presents arterial blood pressure and the electrocardiogram in a mouse where a precisely timed single electrical pulse (#, inset) was within the vulnerable zone of the cardiac cycle and caused ventricular tachycardia. Ventricular tachycardia was identified on the electrocardiogram as rapid, wide QRS complexes with concomitant fall in arterial blood pressure. In Panel B, a second precisely timed electrical pulse (*, inset) was within the protective zone of the cardiac cycle and blocked the induction of ventricular tachycardia caused by the earlier stimulus.

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  Figure 4. Presents 0.5 sec analog recordings of arterial pressure and the electrocardiogram with a precisely timed stimulus arriving early within the refractory period (11.75 msec after the R‐wave; Panel A) and outside the refractory period (19.75 msec after the R‐wave; Panel B). A pulse arriving within the refractory period failed to evoke a cardiac response (Panel A). A pulse arriving outside the refractory period depolarized the heart and elicited a compensatory pause but failed to cause ventricular tachycardia (Panel B). The Y scale on the electrocardiogram figures was expanded to display the details of the electrocardiogram and resulted in the stimulus shown off scale.

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  Figure 5. Box plot of the vulnerable and protective zone. The vulnerable zone is a period within the cardiac cycle during which a precisely timed single electrical impulse caused ventricular tachycardia. The protective zone is a period within the cardiac cycle during which a precisely timed stimulus blocked the induction of ventricular tachycardia caused by an earlier stimulus within the vulnerable zone. The central box represents the values from the first and third quartiles (25–75 percentile). The vertical lines (whiskers) denote minimum and maximum values. The bold center line in each box plot represents the median value.

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  Figure 6. Box plots of arterial pressure (Panel A) and heart rate (Panel B) before the stimulus, after the stimulus which induced ventricular tachycardia (Ventricular Tachycardia), and following ventricular tachycardia (Recovery). The central box represents the values from the first and third quartiles (25–75 percentile). The vertical lines (whiskers) denote minimum and maximum values. The bold center line in each box plot represents the median value. *P < 0.05, Prestimulus versus Ventricular Tachycardia; #P < 0.05, Prestimulus versus Recovery

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  Figure 7. Box plots of arterial pressure (Panel A) and heart rate (Panel B) before (Prestimulus) and after (Recovery) the stimulus which did not cause ventricular tachycardia. The central box represents the values from the first and third quartiles (25–75 percentile). The vertical lines (whiskers) denote minimum and maximum values. The bold center line in each box plot represents the median value.

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  Figure 8. Presents the relationship between the vulnerable zone and heart rate (Panel A) and the protective zone and heart rate (Panel B) during the two protocols. Linear regression analysis revealed that heart rate was significantly correlated with the vulnerable zone; however, the relation was not as strong during determination of the protective zone.

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  Figure 9. Presents original recordings of the ECG during the ischemia‐reperfusion protocol without (Panel A) and with a precisely timed single electrical pulse within the protective zone of each cardiac cycle (Panel B). Each panel presents 0.5 sec of the ECG before occlusion (without stimulus; Panel A and with stimulus; Panel B), at 1, 2, 3, and 3.5 min of occlusion, and at 10, 20, 30, and 40 sec after occlusion (Postrelease). Acute coronary artery occlusion induced rapid changes in the ECG (peaked T‐wave and ST‐segment elevation, (Panel A). Upon reperfusion, all animals experienced ventricular tachycardia (Panel A). On an alternate day (Panel B), coronary artery occlusion was repeated with a precisely timed single electrical pulse within the protective zone of each cardiac cycle. The precisely timed single electrical pulse within the protective zone blocked reperfusion‐induced ventricular tachycardia in every animal (Panel B). ECG, electrocardiogram.