Phase locking, period doubling bifurcations and chaos in a mathematical model of a periodically driven oscillator: a theory for the entrainment of biological oscillators and the generation of cardiac dysrhythmias.

A mathematical model for the perturbation of a biological oscillator by single and periodic impulses is analyzed. In response to a single stimulus the phase of the oscillator is changed. If the new phase following a stimulus is plotted against the old phase the resulting curve is called the phase transition curve or PTC (Pavlidis, 1973). There are two qualitatively different types of phase resetting. Using the terminology of Winfree (1977, 1980), large perturbations give a type 0 PTC (average slope of the PTC equals zero), whereas small perturbations give a type 1 PTC. The effects of periodic inputs can be analyzed by using the PTC to construct the Poincaré or phase advance map. Over a limited range of stimulation frequency and amplitude, the Poincaré map can be reduced to an interval map possessing a single maximum. Over this range there are period doubling bifurcations as well as chaotic dynamics. Numerical and analytical studies of the Poincaré map show that both phase locked and non-phase locked dynamics occur. We propose that cardiac dysrhythmias may arise from desynchronization of two or more spontaneously oscillating regions of the heart. This hypothesis serves to account for the various forms of atrioventricular (AV) block clinically observed. In particular 2:2 and 4:2 AV block can arise by period doubling bifurcations, and intermittent or variable AV block may be due to the complex irregular behavior associated with chaotic dynamics.