Description of heart-rate variability data in accordance with a physiological model for the genesis of heartbeats.
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Biomedical subjects
Publications and source records attributed to J M Karemaker.
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The short-latency effect on heart rate of peripheral nerve stimulation was studied in decerebrate cats. Selective activation (17-40 microA, 100 Hz, 1 s long) of low-threshold fibers in the nerves to the triceps surae muscle yielded isometric contractions of maximal force that were accompanied by a cardiac cycle length shortening within 0.4 s from the start of stimulation. This effect was abolished by pharmacologically induced neuromuscular blockade. The cardiac cycle length shortening during paralysis reappeared after a 6- to 10-fold increase of the stimulation strength. Cutaneous (sural) nerve stimulation (15-25 microA, 100 Hz, 1 s long) elicited reflex contractions in the stimulated limb, which were also accompanied by a cardiac acceleration with similar latency. Paralysis prevented the reflex contractions and reduced the cardiac response in some cats and abolished it in others. The response reappeared in either case after a 5- to 10-fold increase of the stimulus strength. It is concluded that muscle nerve and cutaneous nerve activity both cause a similar cardiac acceleration with a latency of less than 0.4 s. The response to muscle nerve stimulation is elicited by activity in group III afferents. It is excluded that the cardiac response to nerve stimulation is secondary to a change in the respiratory pattern.
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In 10 unsedated normotensive subjects, low-level bilateral electrical stimulation of the carotid sinus nerves (0.35 ms, 1-2 V) was applied with frequencies of 20-200 Hz for therapeutic purposes. Both peak and steady-state reflex effects increased with the stimulus rate up to 80 Hz. After 1 min of stimulation, the largest fall of arterial pressure (21.0 +/- 5.8%, mean +/- S.D.) was produced by stimulus frequencies of 80-120 Hz. Right atrial pacing did not modify the results. After 1 min of stimulation at 200 Hz, the arterial pressure fall was reduced to 13.6 +/- 5.2% (P less than 0.001), whereas peak effects, reached after 15-40 s, were near maximal. The reduction of the depressor response emerged after about 10 s of stimulation and was complete after about 1 min. Peak RR-interval prolongation occurred within 10 s and showed no adaptation. Comparison of continuous stimulation and R-wave-triggered intermittent stimulation in 3 subjects suggested that the reflex effect was determined by the mean stimulus frequency. We conclude that frequency limitation in the baroreceptor reflex begins when the stimulus rate exceeds about 80 Hz. It leads to a frequency-dependent, gradual adaptation of the reflex effects when the stimulus rate exceeds 120 Hz. This conclusion is limited to the part of the reflex that is subserved by myelinated afferent fibers.
In 11 normotensive subjects with coronary artery disease, low intensity electrical stimulation of the carotid sinus nerves (CSN) was triggered by the R-wave in the electrocardiogram with an adjustable delay. The latent period was estimated between the start of CSN stimulation and the onset of the reflex-PP-interval prolongation and, during right atrial pacing, the onset of the reflex fall of diastolic arterial pressure and prolongation of the AV-interval. The latency to the reverse changes was determined after switching CSN stimulation off. The PP-interval changes started after a latency of 0.5-0.6 s. This latency was independent of the respiratory phase and it was independent of the directional change of the afferent activity. AV-interval changes started after about 1 s. When heart rate was fixed, arterial pressure changes started after 2-3 s. It is estimated that central processing of baroreceptor afferent activity may require 0.25 s in the human.
Electrical stimulation of the carotid sinus nerves was applied during diagnostic catheterization of two patients who had coronary artery disease. The immediate reflex prolongation of the atrioventricular (AV) interval was due to prolongation of the AH interval only and was roughly parallel to the reflex RR interval prolongation evoked without atrial pacing. After cholinergic block, the reduced prolongation of both the RR interval and the AV interval caused by reflex inhibition of sympathetic tone followed a time course similar to the arterial pressure decrease. This is the first demonstration in man of the parallel baroreflex effects on the sinoatrial node and the AV node.
An implantable stimulating electrode was developed for baroreceptor afferent nerves in the freely moving rabbit (nerve diam 0.1-0.2 mm). It consists of highly flexible electrode leads (coiled Pt-Ir wire) and silicone rubber (Silastic) as insulation. The electrodes were shown to be effective for up to 245 days after implantation in the neck. Electrode failure was due to dislodgment of the electrode (early failures) or (ultimately) cable breakage. Heart rate and blood pressure responses of separate and combined stimulation of depressor and carotid sinus nerves are shown. In vitro studies demonstrated some current leakage from the electrode to surrounding tissues, but the in vivo measurements show the validity of the method.
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