Electrophysiological Characterization of Human Atria: The Understated Role of Temperature

Figures

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  Figure 1. Action potentials obtained using region-specific models for different parts of the atria, under (A) control and (B) chronic AF (cAF) remodeled conditions. The dotted black line represents the AP from crista terminalis (CT), the dashed orange line represents the AP from the pectinate muscle region (PM); the dashed maroon line represents the AP from left and right atrial appendages (APG), and the thick dashed blue line represents the AP from the left and right atrioventicular regions (AVR). The rest of the atria, i.e., the Bachmann's bundle (BB), fossa ovalis (FO), pulmonary veins (PV), the isthmus of the right atrium (RIS) and the atrial working myocardium (AWM) is modeled using a single set of parameters. The corresponding AP is shown using a dotted blue line (AWM*).

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  Figure 2. Segmentation of the atria according to AP-based (A,B) and conduction-based (C,D) heterogeneity, as assigned by Tobón et al. (2013).

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  Figure 3. Temperature-dependence of RMP, and minimum stimulus (χ, in Coulombs) required to produce an action potential, in normal (A,C) and remodeled (B,D) cardiac cells, isolated from different regions of the human atria (CT, AVR, APG, PM, and AWM*).

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  Figure 4. Comparison of region-specific temperature-dependencies of AP characteristics (A) APD90, (B) APD50, and (C) notch depth (dnotch), and (D) conduction velocity (CV) under normal (Control) conditions.

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  Figure 5. Temperature-dependence of APD90 restitution curves recorded from (15.36 × 3 mm) tissue strip containing cells from (A) CT, (B) BBFO, (C) PM, (D) PV, (E) RIS, (F) AWM, (G) APG, and (H) AVR, respectively. Restitution was measured using the dynamic S1-S2 protocol, whereby, each tissue strip was first allowed to reach a steady state at a given temperature (5° < T < 45°C). Then a series of 20 S1 pulses were applied at the left end of the strip, at a pacing frequency of 1 Hz. Finally, a 21st stimulus (S2) was applied in a similar manner, but after a variable diastolic interval (DI). Our results indicate the occurrence of a phenomenon similar to a first order state transition, at very low temperatures in most atrial regions. At high (T > 40°C), the APD restitution curves exhibit a negative slope.

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  Figure 6. Analysis of the APD restitution curves for all atrial regions. Temperature-dependence of (A) DImin, (B) APDmin, and (C) DIc, as measured from CT, BBFO, PM, PV, RIS, AWM, APG, and AVR. DImin shows a general hyperbolic decrease with increase in temperature. APDmin on the other hand, increases slightly with decrease in temperature, reaching a maximum around 20°C and then decreasing again to approximately its value at 37°C. The sudden large deviation in APDmin around 15−20°C for AWM arises from the atypical behavior of its corresponding APD restitution curve (see Figure 5F). DIc increases almost linearly with decrease in temperature for each region, although the rate of increase is region-dependent.

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  Figure 7. Temperature-dependence of CV restitution curves recorded from (15.36 × 3 mm) tissue strips containing cells from (A) CT, (B) BBFO, (C) PM, (D) PV, (E) RIS, (F) AWM, (G) APG, and (H) AVR, respectively. Restitution was measured using the dynamic S1-S2 protocol (see section 2 for details). Our results show that CV is more or less independent of DI for most regions (PV, RIS, AWM, APG, and AVR), at all temperatures. However, in some regions (CT, BBFO, and PM), CV exhibits initial fluctuations at low DI at moderate temperatures.

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  Figure 8. Propagation of a plane wave through the human atria at normal body temperature (37°C).

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  Figure 9. Formation of a pair of counter-rotating scroll waves by S1-S2 cross-field protocol at 37°C under cAF-remodeled conditions.

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  Figure 10. Scroll wave dynamics in the remodeled human atria, under the effect of global cooling at temperatures (A) 20°C, (B) 15°C, (C) 10°C, and (D) 5°C. Moderate cooling (15−20°C) leads to stabilization of the initial scroll wave, with reduced period. At ~ 10°C, the scroll wave breaks up. The atria then supports multiple scroll waves that maintain a state of sustained AF. Severe cooling (~ 5°C) leads to suppression of the scroll wave, within 200 ms.