Background We investigated whether respiratory sinus arrhythmia (RSA) in healthy humans originated from central neuronal oscillations or from peripheral baroreceptors responding to respiratory changes in venous return. Methods and Results During subjects’ controlled breathing we used sinusoidal neck suction to influence RSA (spectral analysis of RR interval). In 11 subjects, 20-second apnea greatly reduced RSA, which was restored by neck suction at the frequency of respiration. Counteracting the respiration-induced cycles of carotid blood pressure decreased RSA in 13 subjects (from 2136±682 to 1372±561 ms 2 , P <.01). The critical phase of this neck suction was constant for each subject at around the phase shift (with regard to respiration-related fluctuations of blood pressure) best for smoothing respiratory (mechanical) changes in blood pressure. Suction of a nonbaroreceptor area (the thigh) did not affect RSA. In 4 subjects, to separate the effects of peripheral baroreceptor afferents from respiration-entrained central oscillation (15 breaths/min), we cycled the neck suction at 12 cycles/min. Increasing neck suction from −7 to −30 mm Hg increased the ratio of the power of the 12 cycles compared with the 15-cycle RSA oscillation in RR interval spectral analysis from 0.26 to 2.57. A 12-cycle/min suction of an area other than the neck had little effect on the RR interval spectrum. Conclusions RSA can be mimicked or reduced by stimulation of arterial baroreceptors with cycles of appropriately phased neck suction at the frequency of respiration. This suggests an important influence of the arterial baroreceptors in the generation of RSA in conscious humans.
To assess the relative roles of neural and nonneural mechanisms in respiratory sinus arrhythmia (RSA) at rest and during exercise (steady-state supine cycle ergometry at 25% of peak oxygen uptake), we studied 10 healthy men (mean age 21 +/- 1 yr) before (control) and during ganglion blockade (GB) with trimetaphan camsylate (3-5 mg/min i.v.). GB was confirmed by the abolition of the reflex bradycardia in response to intravenous phenylephrine and of the blood pressure rise with the cold pressor test. RSA was calculated from the power of the spectral component of the R-R interval variability centered at the breathing frequency. GB decreased but did not abolish RSA. At rest, this nonneural component of RSA was negligible, accounting for < 1% of the control RSA. During GB, exercise did not affect RSA significantly. However, because control RSA was decreased by exercise, the proportion of nonneural RSA increased by 32% (range from 17 to 75%). These results indicate that as the vagal tone decreases with exercise, an increasing proportion of RSA is due to nonneural mechanisms.
Background: The incidence of sudden cardiac death is maximal in the morning hours. Although ventricular arrhythmias have been implicated as a potential mechanism, and several neurohumoral factors affecting myocardial excitability have been shown to be raised in the early morning hours, it is not known if there is any circadian variation in the dynamics of ventricular repolarization when studied on a beat‐to‐beat basis. The objective of this study was to examine the range, diurnal variations, and circadian distribution of the variability of the QT interval in healthy subjects. Method: We developed and validated a new method for continuous measurement of QT intervals from 24‐hour Holter recordings. The QT intervals measured semi‐automatically were corrected by a linear regression formula derived independently for each patient from his own QT and RR values in 32 healthy males (20 ± 0.4 years). QT variability was assessed by the mean standard deviation of the average of consecutive uncorrected QT intervals (SDA‐QT Index) and corrected QT intervals (SDA‐QTc index) over 5‐minute segments. The rate‐dependent changes of the QT interval were studied as a function of the slope of the regression line between the QT and RR values. Results: The average QTc range was mean (SD) 79 (± 28) ms; the average maximal QTc interval was 481 (± 24) ms. The 95% upper confidence limit for the mean 24‐hour QTc interval was 443 ms. The RR, QT, and QTc intervals were longer, while the SDA‐QT and SDA‐QTc indices were shorter during sleep. Hourly averages of the SDA‐QT and SDA‐ QTc index revealed a sudden increase in QT variability in the first hour of waking (P < 0.0001 and P = 0.006). Conclusion: The dynamic behavior of the QT interval shows significant diurnal variations. The maximal QTc interval over 24 hours is longer than previously assumed. The period shortly following awakening is characterized by a peak in the variability of the QT interval. These changes may be indicative of autonomic instability during the early waking hours and correspond with the peak incidence of sudden arrhythmic death.
Totally implantable drug delivery devices have been shown to be safe and effective in the delivery of drugs both systemically and regionally. Applications have been developed for continuous infusions of drugs and are currently being developed for variable flow rates with more sophisticated programmable pumps. Some of the potential benefits of such devices include improved drug efficacy with reduced systemic toxicities, more controlled dosing of drugs, improved quality of life, delivery of proteins and peptides, and individualized patient dosing. The potential exists for creating biofeedback closed loop therapies for diabetes, cardiovascular diseases, and some central nervous system diseases in the future.
The effect of dobutamine on cardiac function of dogs was investigated. Sixteen dogs were submitted to cardiopulmonary bypass. The aorta of each dog was cross-clamped for 1 hour; attempt was not made to perfuse the heart. After 1 hour, 8 of the 16 dogs were randomly selected and treated with dobutamine (5 mug/kg/min). The other 8 dogs were designated the control group and were given placebo. Postperfusion failure and death were used as end point criteria. Dogs given dobutamine responded remarkably well, with significantly decreased postperfusion low output syndrome. Evidence of cardiac function 5 minutes after the removal of the bypass was the criterion used to determine survival of the surgical cross-clamp procedure; however, this did not necessarily indicate survival of the dog. Of the 8 dogs given dobutamine, 6 (75%) survived the surgical cross-clamp, whereas of the 8 dogs not given dobutamine, 3 (37.5%) survived the surgical procedure. Seemingly, the effect of dobutamine is not mainly chronotropic, but is rather a direct aid to myocardial strength.
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