Defibrillate You Later, Alligator: Q10 Scaling and Refractoriness Keeps Alligators from Fibrillation

Abstract

Effective cardiac contraction during each heartbeat relies on the coordination of an electrical wave of excitation propagating across the heart. Dynamically induced heterogeneous wave propagation may fracture and initiate reentry-based cardiac arrhythmias, during which fast-rotating electrical waves lead to repeated self-excitation that compromises cardiac function and potentially results in sudden cardiac death. Species which function effectively over a large range of heart temperatures must balance the many interacting, temperature-sensitive biochemical processes to maintain normal wave propagation at all temperatures. To investigate how these species avoid dangerous states across temperatures, we optically mapped the electrical activity across the surfaces of alligator (Alligator mississippiensis) hearts at 23°C and 38°C over a range of physiological heart rates and compare them with that of rabbits (Oryctolagus cuniculus). We find that unlike rabbits, alligators show minimal changes in wave parameters (action potential duration and conduction velocity) which complement each other to retain similar electrophysiological wavelengths across temperatures and pacing frequencies. The cardiac electrophysiology of rabbits accommodates the high heart rates necessary to sustain an active and endothermic metabolism at the cost of increased risk of cardiac arrhythmia and critical vulnerability to temperature changes, whereas that of alligators allows for effective function over a range of heart temperatures without risk of cardiac electrical arrhythmias such as fibrillation, but is restricted to low heart rates. Synopsis La contracción cardíaca efectiva durante cada latido del corazón depende de la coordinación de una onda eléctrica de excitación que se propaga a través del corazón. Heterogéidades inducidas dinámicamente por ondas de propagación pueden resultar en fracturas de las ondas e iniciar arritmias cardíacas basadas en ondas de reingreso, durante las cuales ondas espirales eléctricas de rotación rápida producen una autoexcitación repetida que afecta la función cardíaca y pude resultar en muerte súbita cardíaca. Las especies que funcionan eficazmente en una amplia gama de temperaturas cardíacas deben equilibrar los varios procesos bioquímicos que interactúan, sensibles a la temperatura para mantener la propagación normal de ondas a todas las temperaturas. Para investigar cómo estas especies evitan los estados peligrosos a través de las temperaturas, mapeamos ópticamente la actividad eléctrica a través de las superficies de los corazones de caimanes (Alligator mississippiensis) a 23°C and 38°C sobre un rango de frecuencias fisiológicas del corazón y comparamos con el de los conejos (Oryctolagus cuniculus). Encontramos que a diferencia de los conejos, los caimanes muestran cambios mínimos en los parámetros de onda (duración potencial de acción y velocidad de conducción) que se complementan entre sí para retener longitudes de onda electrofisiológicas similares a través de los rangos de temperaturas y frecuencias de ritmo. La electrofisiología cardíaca de los conejos acomoda las altas frecuencias cardíacas necesarias para mantener un metabolismo activo y endotérmico a costa de un mayor riesgo de arritmia cardíaca y vulnerabilidad crítica a los cambios de temperatura, mientras que la de los caimanes permite un funcionamiento eficaz en una serie de temperaturas cardíacas sin riesgo de arritmias eléctricas cardíacas como la fibrilación, pero está restringida a bajas frecuencias cardíacas.

Fig. 1

Effect of temperature and BCL on APD and morphology in rabbit (A and C) and alligator (B and D). (A and B) Representative APs for all measured BCLs overlaid to accentuate BCL and temperature dependence. As BCL is shortened, APD likewise decreases. (C and D) Two subsequent APs from one BCL are overlaid to show beat-to-beat variation in AP morphology at 38°C (left) and 23°C (right). Note that x-axis scales are different for the two species.

Fig. 2

Snapshots of the propagation of an action potential across similar sized regions of tissue in rabbit (left) and alligator (right) at 38°C (top) and 23°C (bottom). The difference in wave propagation between temperatures is nearly indistinguishable in the alligator heart, whereas the rabbit heart displays a clear CV reduction in hypothermia. The wavefront of excitation in the alligator is not as discernible as in the rabbit due to a nearly order of magnitude longer depolarization, which results in a “smearing” of the action potential’s wavefront over the alligator’s heart.

Fig. 3

Cardiac electrical wave characteristics in rabbit and alligator at 38°C (red) and 23°C (blue) across BCLs. (A) APD. APDs in rabbit exhibit an increased temperature-dependent divergence at larger BCLs, but alligator APDs are consistently altered by temperature across all BCLs. (B) CV. Reduction of CV at 23°C is substantial in rabbit but negligible in alligator. (C) Action potential wavelength ${\lambda }_{\text{APD}}$. VF occurred in rabbit hearts when stimulated at BCLs for which ${\lambda }_{\text{APD}}$ fell below the ventricular length scale (yellow region below horizontal dashed line). The long VFRP in the alligator prohibited ${\lambda }_{\text{APD}}$ from approaching this critical zone. Insets are magnifications of correspondingly colored regions.

Fig. 4

Temperature coefficients Q₁₀ for cardiac dynamic properties in rabbit and alligator across BCLs for which hearts could be stimulated at both 23°C and 38°C. (A) The Q₁₀ of APD in alligator approaches unity across all BCLs. In rabbit, APD is more greatly affected by the temperature at larger BCLs. (B) CV in rabbit is increasingly sensitive to temperature as BCL is reduced, and CV in alligator shows small temperature sensitivity across all BCLs. (C) Action potential wavelength ${\lambda }_{\text{APD}}$ in alligator is insensitive to temperature across all BCLs. This wavelength in rabbit exhibits strong temperature sensitivity, exacerbated further as BCL is reduced. (D and E) Q₁₀ for all coefficients overlaid for each species. In rabbit (D), Q${}_{10}^{\text{CV}}$ and Q${}_{10}^{\text{APD}}$ become increasingly unbalanced at shorter BCLs, whereas in alligator (E), temperature sensitivities of APD and CV coordinate and preserve a temperature-insensitive ${\lambda }_{\text{APD}}$ across BCLs. Error bars denote 1 SD. Colored traces in A–C denote linear regressions with slopes listed in plots.