Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.     

Interactions between carotid sinus mechanoreceptor and chemoreceptor reflex loops

n-Alkane assimilating yeast, Candida tropicalis YO-148, was grown on an n-alkane-containing medium. A synthetic diet containing 6.8% of dried yeast was fed to rats. The fatty acid composition of adipose tissue and liver fats was determined after a two week feeding period. The percentage of odd-numbered acids increased in the animals fed the yeast diet. Furthermore, it was shown that heptadecenoic acid, the major odd-numbered acid in yeast, was accumulated in neutral lipid fraction of adipose tissue fat. Fatty acid composition of protein isolate prepared from yeast cells had a profile similar to that of the original cells.     

Experimental muscle pain increases the human stretch reflex

In this study we investigated the effect of human experimental muscle pain on H- and stretch reflexes as indicators of changes in muscle spindle sensitivity. Fourteen healthy, male volunteers participated in the study. Muscle pain was produced by infusion of 5% hypertonic saline over a period of 10-15 min in m. soleus and in m. tibialis anterior. Reflexes were elicited in the relaxed and active soleus muscle (10-15 Nm ankle torque) before, during and after muscle pain. Control measurements were made with infusions of 0.9% isotonic saline. Surface electromyograms (EMG) were measured from the soleus muscle, and torque was measured from the ankle joint. With pain in the soleus muscle the mechanical stretch reflex response (ankle torque) increased significantly (P = 0.0007) as compared to before pain. With pain in the tibialis anterior muscle both the mechanical and EMG responses increased significantly (P = 0.001; P = 0.0003) as compared to before pain. The H-reflex showed no significant changes during the infusions in either muscles. This study has demonstrated a muscle pain-related increase in the amplitude of the stretch reflex without a corresponding increase in the H-reflex amplitude. One explanation could be an increased dynamic sensitivity of the muscle spindles during muscle pain caused by an increased firing rate in the dynamic gamma-motoneurones. However, the data could not support the vicious cycle model because the excitability of the alpha-motoneurone pool was unchanged.     

Correlative changes in total vascular capacity and resistance in carotid sinus reflex

To attain a quantitative understanding of carotid sinus reflex control of circulation, we studied the correlation between changes in total vascular capacity (V) and total peripheral resistance (R). We used a newly devised, accurate and simple method to measure changes in V while both mean central venous and arterial pressures being kept constant. In 7 open chest dogs (7-11 Kg, mean 8.9 Kg), bilateral carotid occlusion after vagotomy reduced V by as much as 58 +/- 9 (SE) ml or approximately 8% of total blood volume while R increased by 36 +/- 5% from 0.08 +/- 0.01 mmHg-min/ml. Similar responses were obtained either in the reflex before vagotomy or with infusion of norepinephrine. Mathematical analysis with Poiseuille's law suggested that internal radius of an average resistance vessel decreased approximately 1.5 to 3 times as much as that of an average capacitance vessel. The wall to lumen ratio of the average resistance vessel estimated from the correlation was 0.3 to 0.6, being within physiological range. Therefore, the difference in vascular sensitivity may be partly owing to the wall to lumen ratio of resistance vessels. Moreover, the correlative changes in the capacitance and resistance vessels were elucidated to be significantly responsible for the characteristic hemodynamic changes in carotid sinus reflex.     

Dual adaptation and adaptive generalization of the human vestibulo-ocular reflex

In two experiments, we examined the possibility that the human vestibulo-ocular reflex (VOR) is subject to dual adaptation (the ability to adapt to a sensory rearrangement more rapidly and/or more completely after repeated experience with it) and adaptive generalization (the ability to adapt more readily to a novel sensory rearrangement as a result of prior dual adaptation training). In Experiment 1, the subjects actively turned the head during alternating exposure to a visual-vestibular rearrangement (target/head gain = 0.5) and the normal situation (target/head gain = 0.0). These conditions produced both adaptation and dual adaptation of the VOR but no evidence of adaptive generalization when tested with a target/head gain of 1.0. Experiment 2, in which exposure to the 0.5 gain entailed externally controlled (i.e., passive) whole body rotation, resulted in VOR adaptation but no dual adaptation. As in Experiment 1, no evidence of adaptive generalization was found.     

Functional asymmetries in the stepping reflex of human neonates.

Determined the leading leg in the stepping reflex of 24 infants at average ages of 17, 51, 82, and 105 days. Ss, offspring of right-handed parents, showed a clear tendency to lead with the right leg on all 4 test sessions. It is concluded that the functional asymmetry between the "support leg" and the "leading leg" in adults may have its roots very early in development. (French summary) (10 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynamics of conditioned reflex reorganization in the human visual system

The dymamics of absolute and relative changes in the brightness thresholds of letters recognition was studied in 21 subjects, under conditions of dark adaptation and molecular observation, before and after pairing of one of the letters with electrocutaneous stimulation of the index finger during one session. Isolated electrocutaneous stimulation was applied on the 10th or 35th day after the session. It has been found that after pairings the relative threshold of recognition of the letter previously paired with electrical stimuli (i.e. the threshold in relation to recognition thresholds for the other letters) becomes for three to three and a half hours significantly lower than the initial one. Then there sharply sets in a phase of threshold elevation. Both in the case of double and multiple tests, this phase persists for not less than 35 days. Following an isolated electrical stimulation, a momentary significant lowering of the threshold sets in only for the letter which was paired with it in the first sessions.     

Functional significance of the early component of the human blink reflex.

The relationship between the size of the first electromyographic (EMG) component of the cutaneous blink reflex (Rl) and onset of eyelid closure in human adults was determined in 4 experiments in which R1 size was varied by different means: change in stimulus intensity, paired stimulation, and warning. Two-phase lid movements were frequently seen, with an early small movement followed by a large rapid movement. All experiments showed that larger R1s were associated with shorter latencies of both movements. This covariation was general across participants and was independent of shifts in the excitability of the blink reflex pathways indexed by R1 latency, R2 latency, and R2 area (R2 is the more prolonged, later EMG component). The results indicate that R1 acts first to evoke an early lid movement and second to facilitate eyelid closure by the later R2 burst. Identification of this second behavioral function for R1 aids the interpretation of other findings and encourages its use as a model system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Habituation and sensitization of components of the human eyeblink reflex.

The supraorbital branch of the right trigeminal nerve was stimulated in 5 20–26 yr olds with trains of electric shocks, 10 in each train, with interpulse intervals of 1, 2, or 5 sec. EMG reflex activity in the palpebral musculature was measured to each pulse in the train. Each response consisted of 2 components, a fast brief ipsilateral burst (R1) and a slower prolonged bilateral burst (R2). Over the 10-pulse series, the amplitudes of R1 increased in strength (sensitization), whereas the allied R2 amplitudes declined (habituation). Both of these effects were enhanced as the interpulse interval was reduced. A consideration of the anatomical substrate for each reflex component, together with some other data in the literature, suggests that reflex sensitization occurred in the efferent limb of this brain-stem reflex while, simultaneously, habituation occurred in its central link. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local reflex in microcirculation in human cutaneous tissue

Blood flow in cutaneous tissue measured by the local 133Xenon washout technique decreased about 35 per cent during venous stasis of 40 mmHg in three normal subjects. The response was unaffected by block of the nerve three cm proximally to the labeled area. When the tissue was infiltrated with lidocaine or with phentolamine, blood flow remained constant, indicating that the decrease in blood flow is due to an arteriolar vasoconstrictor response to increase in venous transmural pressure. Local venous stasis elicited a vasoconstrictor response in an adjoining area not affected by the stasis. The response was blocked by lidocaine applied to the side of stasis. In 2 chronically sympathectomized patients, the vasoconstrictor response was abolished in the denervated limbs but present on the non-operated side (1 patient with unilateral sympathectomy). The results indicate that the vasoconstrictor response to an increase in venous transmural pressure is due to a local nervous mechanism involving sympathetic adrenergic fibres, most likely a sympathetic axon reflex.     

Geometric characterization of stenosed human carotid arteries

RATIONALE AND OBJECTIVES: The geometry of stenosed carotid bifurcations was analyzed to determine average representations for several stenosis grades. METHODS: Film angiograms of 62 patients with internal carotid artery stenoses were digitized. Residual lumen boundaries were manually outlined. The outlines were processed with a computer to extract geometric measurements. The measurements were grouped according to stenosis grade and used to create average representations. RESULTS: Accuracy and precision of the outlining technique were +/- 0.020 common carotid diameters (CCD) and +/- 0.025 CCD, respectively. Maximum narrowing of the internal carotid artery occurred at 0.3 CCD +/- 1.5 (mean +/- standard deviation) distal to the flow divider. The region of significant narrowing extended axially 1.2 CCD +/- 1.0. Poststenotic dilatations were observed, with enlargement of 1.3 +/- 0.7 times the normal diameter of the distal internal carotid artery. A tendency toward smaller bifurcation angles with increasing stenosis severity was observed. CONCLUSION: Three-dimensional geometric models could be created for carotid bifurcations that were disease free (normal) and of arbitrary stenosis grade.     

The human H and T reflex methodologies applied to the rat

Homozygotic spasmodic (spd/spd) mice suffer from a motor disorder resembling poisoning by the glycine receptor antagonist strychnine. Here, a point mutation was identified in the glycine receptor alpha 1 subunit gene of the spasmodic mouse which predicts an alanine-to-serine exchange at position 52 of the mature polypeptide. Upon expression in Xenopus laevis oocytes, alpha 1A52S receptor channels displayed reduced responses to glycine, beta-alanine and taurine when compared to recombinant alpha 1 glycine receptors. As glycine receptor content in spinal cord and native molecular weight appeared unaltered, this suggests that the spasmodic phenotype results from an altered neurotransmitter sensitivity of the mutant alpha 1A52S subunit.     

Spatial extension of sudomotor axon reflex sweating in human skin

Acetylcholine (ACh) applied to human skin is known to elicit a sweat response, which consists of a direct muscarinergic (M3) activation of sweat glands and a nicotinic axon reflex response from sudomotor terminals. To visualize the extent of axon reflex sweating after ACh-iontophoresis, iodine starch staining was used. Iontophoresis was performed under occlusion at the peroneal aspects of the lower leg and the center of the foot dorsum of healthy volunteers (n = 10). Ten minutes after stimulation, the area of dark blue staining was recorded by a video camera. Control experiments were performed with saline, histamine, pilocarpine and nicotine iontophoresis. The stained area was measured and the maximum and minimum distance of its boundary from the edge of the iontophoresis probe was determined (maximum/minimum radius). Sizes of stained areas and maximum radii were significantly greater on the lower leg compared to the foot (P < 0.01). The median sizes of the stained areas on the leg were 14.6 cm2 and on the foot dorsum 8.0 cm2. The respective median maximum radii were 3.1 cm on the leg and 2.3 cm on the foot dorsum (median minimum, leg 1.1 cm, foot 0.8 cm). These results match microneurographic findings of innervation territories of sympathetic efferent units. Area sizes of stained skin showed a close correlation between both stimulation sites (R = 0.96, P < 0.01), i.e. the sizes of sweat responses on leg and foot show a constant relation (foot/leg = 0.57) in spite of their great interindividual variability. This novel technique of establishing sweat responses provides information on the size of sudomotor innervation territories and may be useful for clinical studies in patients with suspected impairment of sympathetic functions.     

Late facilitation of the human soleus H reflex induced by sustained isometric maneuver

Isolated tetralogy of Fallot (TF) has a multifactorial mode of inheritance in most cases, and recurrence risk rates of 2.5-3% have been attributed to first degree relatives of an affected child. In a subgroup of patients with a strong family history, the transmission of a monogenic trait has been suspected. Microdeletion 22q11 (del(22q11)) can cause TF in the setting of DiGeorge and velocardiofacial syndromes, and has also been related to familial conotruncal cardiac defects. Empirical risk figures in families after exclusion of del(22q11) have never been calculated. We have investigated the overall occurrence of congenital heart defect (CHD) in relatives of 102 patients with isolated non-syndromic TF previously screened for del(22q11). Our results show that the frequency of CHD is 3% in sibs, 0.5% in parents, 0.3% in grandparents, 0.2% in uncles or aunts, and 0.6% in first cousins. The recurrence risk rate for sibs in our series is the same as that previously estimated, indicating that after exclusion of patients with del(22q11) genetic counselling to patients with isolated TF should not be modified. A high concordance rate among our affected sibs has been documented. Gene(s) different from those located on chromosome 22q11 must be involved in causing familial aggregation of non-syndromic TF in these cases.     

The influence of gender on the masseter electromyographic jaw-jerk reflex in young human subjects

The purpose of this study was to investigate the effect of gender on the masseteric jaw-jerk reflex, evoked in a sample of nine male and nine female young subjects. Electromyographic jaw-jerk recordings elicited by chin-taps in the relaxed masseter muscle of the preferred chewing side, were obtained using a computerized recording and analysis system. In both groups, a jaw-jerk reflex was recorded in 95.56% out of the total number of chin-taps. The mean latency was significantly shorter in the females (5.75 ms) than in the males (6.14 ms, P = 0.0045), while the amplitude of the reflex was significantly higher in the females (P = 0.0005). No significant differences were found in the mean duration between males (6.86 ms) and females (6.73 ms). It was concluded that sex variation should be taken into consideration in the interpretation of the jaw-jerk reflex.     

Stretch reflex and servo action in a variety of human muscles

1. In the long flexor of the thumb the latency of the stretch reflex and of other manifestations of servo action is some 45 msec, roughly double the latency of a finger jerk. 2. Tendon jerks are feeble or absent in the long flexor of the thumb even in subjects with brisk long-latency stretch reflexes in this muscle. This, and other facts, suggests that the nervous mechanism of the tendon jerk is different from that of the stretch reflex. 3. A muscle that has feeble tendon jerks may show a late component in the response to a tendon tap, with a latency similar to that of the long-latency stretch reflex. 4. On the hypothesis that the excess latency of the stretch reflex over that of a tendon jerk is because the stretch reflex employs a cortical rather than a spinal arc, the excess would be expected to be larger in magnitude for the long flexor of the big toe and smaller for the jaw closing muscles. This is confirmed, 5. An alternative hypothesis that the long latency of stretch reflexes in thumb and toe is because they are excited by slow-conducting afferents is made improbable by the finding that stretch reflexes with an equal or greater excess latency are also found in proximal arm muscles. 6. The long-latency stretch reflex in proximal muscles was seen most distinctly in a healthy subject who happened to have feeble or absent tendon jerks. In ordinary subjects there is often a large, short-latency, presumably spinal component of the stretch reflex in proximal muscles; and short-latency responses to halt and release are also seen, The significance of this spinal latency servo action in proximal muscles remains to be explored. 7. The Discussion argues that the available data on conduction time to and from the cerebral cortex are compatible with the hypothesis that the long-latency component of the stretch reflex uses a transcortical reflex arc, and that none of the experiments described in the present paper are inimical to this view.     

Alterations in reflex function contributing to syncope: orthostatic hypotension, carotid sinus hypersensitivity and drug-induced dysfunction

Orthostatic hypotension and related neurologic symptoms are frequently encountered in clinical practice. The maintenance of appropriate blood pressure and heart rate responses upon assuming the upright posture are dependent upon: 1. intact mechanical (venous valves) mechanisms, 2. functioning arterial and cardiopulmonary baroreceptors, 3. normal peripheral neural pathways, 4. normal central neural integration, and 5. appropriate neurohormonal secretion. Dysfunction at one or more of these loci may facilitate the occurrence of orthostatic hypotension and syncope. In general, the mechanisms of orthostatic hypotension may be divided into three categories. In the first category, processes interfere with normal compensatory responses to upright posture. Examples of this mechanism include age related autonomic changes, diabetic neuropathy and central nervous system disease such as Shy-Drager syndrome. The second principal mechanism involves overwhelming otherwise normal reflexes by an intense orthostatic stimulus. An obvious example of this mechanism is syncope related to hemorrhage. A final category of orthostatic hypotension relates to interference with reflex responses by drugs that may limit vasoconstriction, heart rate or cardiac output adjustments or exaggerate venous pooling. These are commonly used medications such as vasodilators, beta-adrenergic blockers and nitrates. The treatment of orthostatic hypotension revolves around the recognition of underlying causes or contributing factors amenable to correction or avoidance. Other helpful treatment options include nocturnal head-up tilting and mineralocorticoids, both of which help to expand blood volume. Many other therapeutic agents have been tried in small and selected patient populations, often with disappointing results. While many of the drugs available (phenylephrine, ephedrine, tyramine, dihydroergotamine) can improve upright blood pressure, side effects are common, and supine hypertension is problematic in many patients. Interventions of this type should be carefully initiated in a monitored setting. The carotid sinus is an important component of a neural control system responsible for heart rate and blood pressure homeostasis. Excessive heart rate and blood pressure responses to distortion of the carotid sinus are the basis for the carotid sinus syndrome (CSS). Patients with CSS tend to be elderly males and local pathology in the neck is frequently involved. Atherosclerotic coronary artery disease and hypertension are important clinical correlates. Two major categories of carotid sinus hypersensitivity (CSH) are recognized: cardioinhibitory and vasodepressor. Cardioinhibitory CSH is the most common, and in its purest form consists of sinus bradycardia or arrest, asystole or AV block during carotid sinus massage. This vagally-mediated response is eliminated by atropine. Cardiac pacing is nearly universally successful in preventing severe symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)