Effects of fibroblast-myocyte coupling on the sinoatrial node activity: A computational study.

While the sinoatrial node (SAN) is structurally heterogeneous, most computer simulations of electrical activity take into account SAN pacemaker cells only. Our aim was to investigate how fibroblasts affect the SAN activity. We simulated the rabbit sinoatrial node accounting for differences between central and peripheral pacemaker cells, and for fibroblast-myocyte electrical coupling. We have observed that only if fibroblast-myocyte coupling is taken into account, (1) action potential is initiated in the central part of the SAN (within 1.2 mm of the center of simulated tissue); otherwise, leading centers are located on the periphery; (2) few (1 to 6) leading centers initiate action potential in the SAN; otherwise, we observed more than 8 leading centers; (3) acetylcholine superfusion results in a shift of leading centers toward the SAN periphery; and (4) sinus pauses up to 1.9 second follow acetylcholine superfusion. We observed negligible effect of fibroblast-myocyte coupling on the period of SAN activation. We conclude that fibroblast-myocyte coupling may explain action potential initiation and propagation from the center of the SAN observed in experimental studies, while atrial load on the peripheral SAN fails to explain this fact.

Computer simulations of reentrant activity in the rabbit sinoatrial node.

With the aid of detailed computer simulations, we have estimated distributions of membrane potential and ionic currents in the core region of a sinoatrial node reentry. We observe reduced amplitudes of the measured quantities in the core; the core sizes for potential and currents did not always coincide. Simulations revealed that acetylcholine, when applied in the vicinity of unstable reentry, attracted the reentry to become the core and to stabilize its rotation. Anatomically detailed simulations of sinoatrial node and surrounding atrial tissue revealed that reentry always rotated around small strips of connective tissue. Acetylcholine superfusion over superior part of the sinoatrial node resulted in a drift of reentry in the cranial direction. Under the latter conditions, reentry may coexist with the pacemaker in the caudal part of the sinoatrial node. Copyright © 2016 John Wiley & Sons, Ltd.

Hibernator Citellus undulatus maintains safe cardiac conduction and is protected against tachyarrhythmias during extreme hypothermia: possible role of Cx43 and Cx45 up-regulation.

BACKGROUND: Most mammals experience cardiac arrest during hypothermia. In contrast, hibernators remain in sinus rhythm even at body temperatures of 0 degrees C. OBJECTIVES: The purpose of this study was to quantify electrical activity and connexin expression in the heart of hibernating Siberian ground squirrel Citellus undulatus. METHODS: Optical imaging and microelectrode recordings were conducted in Langendorff-perfused hearts and isolated papillary muscles of summer active (SA, n = 19), winter hibernating (WH, n = 21), interbout arousal (IBA, n = 12), and winter active (WA, n = 3) ground squirrels and rabbits (n = 14) at temperatures from +37 degrees C to +3 degrees C. RESULTS: All studied SA and WH hearts maintained spontaneous sinus rhythm, safe propagation through the entire conduction system, and normal pattern of ventricular excitation at all temperatures. However, three of the seven IBA and all rabbit hearts lost excitability at 10 degrees C +/- 1 degrees C and 12 degrees C +/- 1 degrees C, respectively. In WH, SA, and IBA ground squirrels, temperature reduction from 37 degrees C to 3 degrees C resulted in a 10-fold slowing of ventricular conduction velocity and increased excitation threshold. At any temperature, WH ventricles had faster conduction velocity and lower excitation threshold compared with SA and IBA. Immunolabeling demonstrated that connexin43 (Cx43) was significantly up-regulated in WH and WA compared with SA myocardium: Cx43 area density was 12.4 +/- 1.3, 15.0 +/- 3.0 and 8.6 +/- 1.1 microm(2)/1,000 microm(2), respectively. Moreover, Cx45 was expressed in the WH but not in the SA or WA ventricles. CONCLUSION: Hibernator Citellus undulatus has evolved to maintain safe conduction at extreme hypothermia via up-regulation of Cx43 and Cx45 in order to protect the heart against arrhythmia associated with hypothermia.

Spatiotemporal dynamics of damped propagation in excitable cardiac tissue.

Compared to steadily propagating waves (SPW), damped waves (DW), another solution to the nonlinear wave equation, are seldom studied. In cardiac tissue after electrical stimulation in an SPW wake, we observe DW with diminished amplitude and velocity that either gradually decrease as the DW dies, or exhibit a sharp amplitude increase after a delay to become an SPW. The cardiac DW-SPW transition is a key link in understanding defibrillation and stimulation close to the refractory period, and is ideal for a general study of DW dynamics.