Advanced electrocardiographic predictors of mortality in familial dysautonomia.

OBJECTIVE: To identify electrocardiographic predictors of mortality in patients with familial dysautonomia (FD). METHODS: Ten-minute resting high-fidelity 12-lead electrocardiograms (ECGs) were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict mortality over a subsequent 4.5-year period, including representative parameters of heart rate variability (HRV), QT variability (QTV), T-wave complexity, signal averaged ECG, and 3-dimensional ECG. RESULTS: Four of the 14 FD patients died during the follow-up period, three with concomitant pulmonary disorder. Of the ECG parameters studied, increased non-HRV-correlated QTV and decreased HRV were the most predictive of death. Compared to controls as a group, FD patients also had significantly increased ECG voltages, JTc intervals and waveform complexity, suggestive of structural heart disease. CONCLUSION: Increased QTV and decreased HRV are markers for increased risk of death in FD patients. When present, both markers may reflect concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea.

Transient ventilatory and heart rate responses to moderate nonabrupt pseudorandom exercise.

Dynamic responses of inspired minute ventilation, CO2 and O2 end-tidal gas fractions, and heart rate were obtained from six normal human volunteers in response to a complex dynamic exercise challenge. Subjects pedalled a chair ergometer at constant frequency. The retarding torque applied to the ergometer pedals was controlled by a low-pass-filtered pseudorandom binary sequence (fPRBS), which provided a complex, nonanticipatory exercise stimulus containing sufficient high- and low-frequency energy to excite the small signal, broadband ventilatory response. The exercise range was chosen to produce a mean level of O2 consumption at or below 50% maximum O2 consumption. Cross-covariant analysis of the fPRBS exercise with breath-by-breath ventilation provided an estimate of the dynamic (impulse) response to exercise, which contained both fast phase 1 and slow phase 2 components. The initial, phase one, hyperpnea occurred within the same breath as the exercise transition and preceded a hypocapnic response. The phase one hyperpnea represented 26% of the total ventilatory response. The secondary, phase 2, hyperpnea was delayed several breaths from the onset of phase 1. It contained slower dynamics and followed a hypercapnic response. Heart rate increased abruptly during phase 1, peaked near the phase 1-to-2 boundary, and then decreased rapidly. The experimental protocol was designed to minimize the subjective response and provide an adequate stimulus for the faster time constants. Results obtained from these experiments were consistent with a nonhumoral induced phase 1 exercise hyperpnea.

Arterial PCO2 response to intravenous CO2 in awake dogs unencumbered by external breathing apparatus.

The steady-state arterial CO2 tension (PaCO2) was examined during control and intravenous CO2 loading in awake dogs unencumbered by any breathing apparatus. The dogs inhaled air while undergoing intravenous CO2 loading, and we estimated the gain, delta VA/delta PACO2. CO2 was introduced into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow was maintained constant at 0.5 l/min. A total of 11 experiments were performed in 3 dogs comprising 93 control observations and 83 CO2 loading observations. Intravenous CO2 produced a significant increase in the steady state PaCO2, a finding consistent with our previous study in tracheostomized awake dogs. We conclude that intravenous CO2 produces hypercapnia in the awake dog with an intact airway unencumbered by external respiratory apparatus.

Experience with a Fourier method for determining the extracellular potential fields of excitable cells with cylindrical geometry.

In this chapter, well-known solutions that utilize a Fourier transform method for determining the extracellular, volume-conductor potential distribution surrounding elongated excitable cells of cylindrical geometry are reformulated as a discrete Fourier transform (DFT) problem, which subsequently permits the volume-conductor problem to be viewed as an equivalent linear-filtering problem. This DFT formulation is fast and computationally efficient. In addition, it lends itself to the application of some rather well-known techniques in linear systems theory (e.g., the DFT for convolution and least mean-square (Wiener) filtering for optimal prediction of a signal in random noise). Two specific examples are employed to demonstrate the utility of this discrete Fourier method: (1) the single, isolated, active nerve fiber in an essentially infinite volume conductor and (2) the isolated, active nerve trunk in a similar type of extracellular medium. In each of these, our DFT method is employed to obtain both the classical "forward" and "inverse" potential solutions for each volume conductor problem. In the case where the single, active nerve fiber is the bioelectric source in the volume conductor, simulated action-potential data from an invertebrate giant axon is utilized, and potentials at various points in the extracellular medium are calculated. The calculated potential distributions in axial distance z, at various radial distances r, are consistent with well-known experimental fact. When the active nerve trunk acts as the bioelectric source, the DFT method provides calculated potential distributions that are fairly consistent with experimental data under a variety of experimental conditions. For example, in these experiments, a special, isolated frog spinal cord preparation is used that permits separate or combined stimulation of the motor and sensory nerve fiber components of the attached sciatic nerve trunk. By manipulating the stimulus intensity applied to the motor (ventral) or appropriate sensory (dorsal) roots of the spinal cord, a variety of multiphasic extracellular volume-conductor potentials can be recorded from the sciatic nerve. The excellent agreement of model-generated and experimental data, regardless of the complexity of surface potential waveform, tends to validate the modeling assumptions and offer encouragement that this computationally efficient DFT method may be usefully employed in volume-conductor problems where both the bioelectric source, and the surrounding volume conductor, are of a much more complicated nature.

Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs.

Ventilatory responses to CO2 inhalation and CO2 infusion were compared in the awake dog. The CO2 was introduced directly into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow, QX, was maintained constant at one of two rates: low, 0.5 l/min; or high, 2.0 l/min. A total of 13 experiments was performed in four dogs comprising 50 control and 25 inhalation and infusion observations at each of the two flow rates. Comparison of CO2-response curve slopes, S = delta V E/delta PaCO2, between CO2 inhalation and infusion showed no significant difference either within or between flow rates. The mean value of S for all conditions was 1.88 l/min per Torr with a 95% confidence interval of 1.66 -2.14. An independent additive ventilatory drive amounting to 28% of low-flow control VE was found at the highflow rate. We conclude that at constant blood flow the responses to both CO2 inhalation and infusion are hypercapnic and not significantly different.