Likewise we found a consistent and progressive decrease in correlation dimension, DFA scaling factor a and SE in CHF dogs as has been shown in human HF. Wilders et al. demonstrate the chaotic fluctuations in beat-to-beat interval of pacemaker cells are due to the stochastic open-close kinetics of the gating of membrane ionic channels. Ionic channel turnover represent a stochastic mechanism contributing to such chaotic variations of cellular characteristics. Furthermore, more chaotic variability probably comes from variations in biochemical and molecular processes involving the concentrations of enzymes, metabolites, and second messengers. Additional biochemical factors involved in the control and modulation of chaotic beating are melatonin, plasma cortisol, growth hormone, catecholamines, angiotensin, renin, aldosterone etc. These factors associated with stochastic channel gating and biochemical processes make HRV more complex and fractal. In CHF dogs, the function of some of these factors that influence RR intervals are turned off or show decreased function, so CHF dogs show decreased complexity and loss of fractal property, which may relate to pathological properties of channels and factors in CHF dogs. Chaos in HRV decreases with progression of CHF patients and in patients with a propensity for adverse arrhythmic events. Moreover the degree of chaos decreases immediately prior to the onset of ventricular arrhythmias. However, little is known about the mechanisms by which decreased chaos in HRV is arrhythmogenic in the failing heart. Dvir et al demonstrated low chaotic HRV is a predictor for cardiac arrhythmogenic events and that pacing of ventricular tissue in a stochastic rather than in a deterministic rhythm exerted a protective antiarrhythmic effect due to a consequence of inherent chaotic HRV. Stochastic ventricular pacing reduced spatial action potential duration heterogeneity, discordant APD alternans and wavebreak initiation. These results suggest that the chaos in HRV provides the heart with a protective mechanism against arrhythmogenesis. Alterations in these parameters with CHF could contribute to EX 527 increased cardiovascular risk in the morning. The current study characterized heart rate dynamics, autonomic oscillation, and nonlinear dynamics in CHF dogs when there is increased risk of cardiovascular events during morning. Healthy HR fluctuations exhibit fractal-like self-similarity and complexity, both of which allow for a broad range of adaptive responses. A reduction in HR fractal properties and complexity, lack of morning enhancement of chaotic activity, loss of time-of-day rhythm in autonomic oscillations and nonlinear dynamics, and blunting of the normal morning transition to high heart rate and sympathetic activity could all contribute to altered regulation of the drug-free arrhythmogenic substrate of this new canine CHF model and its morning surge in ventricular arrhythmias. Development of this large animal arrhythmogenic model of CHF that demonstrates a morning surge in ventricular arrhythmias as well as reduced chaos enable us to further define the underlying mechanisms of VT in the failing heart in ways not possible to achieve in humans.