A nonlinear analytical model of the autonomic basis of heart rate variability (HRV).

The sinoatrial (SA) node is responsible for the initiation of cardiac contractions, and integrates charge across its cell membranes on a beat-to-beat basis mainly through the regulation of slow calcium-sodium channels. The time constant (slope) of this integrator and the firing threshold (voltage) of the SA nodal cells are influenced by inputs from both sympathetic and parasympathetic autonomic neural pathways converging on the heart. A model has been developed in Matlab that accounts for cumulative autonomic effects on the SA node's integrator and non-cumulative effects on it's firing threshold, and includes an assessment of the contribution of noise to both sub-systems. Using the model, an assessment of the effect of an arbitrary number of autonomic inputs is made on the beat-to-beat variability of heart rate. Additionally, the contribution of noise and nonlinear fast channel effects are considered. Assignment of particular autonomic control frequencies results in physiologically realistic heart rate versus time outputs. Physiological heart rate variability modes such as autonomic control spectra in heart rate, mode-locking, and other complex behaviors can be demonstrated. The results of this model may then be compared with physiological data in which autonomic inputs are controlled by paced breathing or other physiological stimulus.

Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse.

Single, short-duration, low-energy pulses of ultrasound were found to elicit distinct modifications of the electrical excitability of myelinated frog sciatic nerve in vitro in a window extending 40-50 ms after pulse termination. These modifications include both enhancement and suppression of relative excitability, the sequence of which generally follows one of two distinct temporal response patterns. The ultrasound pulses were focused, 2-7 MHz, of 500-microseconds duration, and of peak intensities of 100-800 W/cm2. Total absorbed pulse energies were generally less than 100 mJ/g, corresponding to local temperature rises of the nerve trunk of no more than 0.025 degrees C per pulse, thereby precluding bulk heating as a basis of this effect. The observed effects cannot be elicited using either a subthreshold square wave or RF electrical prestimulus, suggesting a unique form of receptivity of the nerve trunk to mechanical perturbation. We present evidence that the low-frequency radiation pressure transient accompanying the envelope of the acoustic pulse is the active parameter in this phenomenon, and postulate that it may act by the gating of stretch-sensitive channels, which have been recently reported in a variety of cell membranes. These results may demonstrate that stretch-sensitive channels in neural membrane can serve to functionally modulate neuro-electric signals normally mediated by voltage-dependent channels, a finding which could suggest new clinical applications of high peak-power, low-total-energy pulsed ultrasound.

Transient modification of nerve excitability in vitro by single ultrasound pulses.

Single pulses of focused ultrasound have been observed to significantly modify neuronal excitability in vitro for a period of 40-50 ms following pulse termination. This window of transient modification includes periods of both relative suppression and enhancement of excitability, the sequences of which generally follow distinct temporal patterns. The ultrasound pulses were focused, 2-7 MHz, nominally of 500 microseconds duration, and of peak intensities of 100-800 W/cm2. Specific absorbed energies were less than 100 mJ/gm, which strongly precludes bulk thermal mechanisms as a basis of this effect. Our current evidence suggests that the low-frequency radiation pressure transient accompanying the envelope of the acoustic pulse is the proximal effector in this phenomenon, acting by the gating of relatively slow stretch-sensitive channels in the neuronal membrane. These observations demonstrate the potential for high peak-power, low total-energy pulses of ultrasound to functionally modulate neuroelectric signals, a finding which could suggest new prosthetic, analgesic, or therapeutic clinical applications.