The effects of lidocaine on cardiac parasympathetic control in normal subjects and in subjects after myocardial infarction

It has been widely accepted that lidocaine has little or no effect on the autonomic nervous system. However, we have previously shown that in dogs with vagally induced atrial fibrillation, lidocaine has a pronounced parasympatholytic effect. To study the possible effect of lidocaine on autonomic cardiac control in humans, we performed spectral analysis of heart rate fluctuations in 19 healthy volunteers, who received an i.v. bolus of lidocaine (1.4 mg/kg), as well as in 13 patients suffering from acute inferior myocardial infarction (IMI) and 13 patients suffering from acute anterior myocardial infarction (AMI), who received therapeutic doses of i.v. lidocaine infusion (4 mg/min). Heart rate variability and respiratory pattern were monitored according to a predetermined protocol, with and without lidocaine. Computing the heart rate power spectrum and integrating over predetermined frequency bands, we focused mainly on the respiratory frequency band, known to predominantly reflect parasympathetic control. The administration of lidocaine resulted in a significant overall increase in mean heart rate: for the healthy control group an increase of 5.5±2.2% (mean±SE), for the IMI group an increase of 9.4±3.5%, and for the AMI group an increase of 8.1±2.9% (p<0.01 for all). Simultaneously, following the administration of lidocaine, there was a decrease in the power of respiratory fluctuations: for the healthy control group a decrease of 38.4±12.5%, for the IMI group a decrease of 46.3±32.9%, and for the AMI group a decrease of 33.9±16.2% (p<0.01 for all). These findings indicate that lidocaine has a consistent and significant parasympatholytic effect on the human heart, in healthy volunteers as well as in patients in the acute phase of myocardial infarction.     

The click-evoked post-auricular myogenic response in normal subjects.

The presence of the posterior auricular myogenic reflex was infectigated in healthy subjects. Click stimuli were delivered alternately to each ear and both ipsilateral and contralateral responses were recorded simultaneously. Smiling and head down position increased the number of responses. With this method, in contrast to previous findings, it was possible to demonstrate bilateral auditory reception in 89% of the 45 subjects studied.     

Subjective effects and vigilance after diazepam and oxazepam in normal subjects.

Twenty-two normal subjects were given single oral doses of diazepam 5 mg, oxazepam 15 mg and placebo in a double-blind cross-over trial. Subjective effects according to a rating scale and performance on a vigilance task were assessed. The results showed a difference between each of the two drugs and placebo, but none between the drugs, with regard to the vigilance test. The results from the rating of subjective effects showed an increase in "tiredness" for both drugs, and a decreased "well-being" for oxazepam.     

Dose response effects of zolpidem in normal geriatric subjects

The dose-related hypnotic effects and effects on memory, performance, and daytime alertness of zolpidem 5, 10, 15, and 20 mg were compared with those of placebo in 30 elderly non-insomniac volunteers in a randomized, placebo-controlled, three-period crossover study. Subjects were randomized into two groups and received either placebo, zolpidem 5 mg, or zolpidem 15 mg or placebo, zolpidem 10 mg, or zolpidem 20 mg for 2 consecutive nights followed by 1 night of placebo during the same 3 nights of 3 consecutive weeks. Polysomnographic results showed statistically significant decreases in sleep latency and increases in sleep efficiency at all doses. Subjective reports also showed improved sleep latency, total sleep time, and sleep quality. REM percent was slightly decreased at doses of 10 and 20 mg. No consistent effects on memory or performance were observed, and the Multiple Sleep Latency Test showed no effects on daytime sleepines. There was no objective evidence of rebound insomnia upon drug discontinuation.     

Stress and age effects on catecholamines in normal subjects

In the first study, plasma and urinary catecholamine levels were studied in healthy young volunteers following exposure to a thermal test (cold-pressor test). Plasma noradrenaline was markedly elevated for some time after the stress ceased. In a second study, a cognitive-conflict task (Stroop's coloured-word conflict test) was used as the stress for groups of young and old, male and female volunteer subjects. There were group differences in the catecholamine responses: all groups except the young females responded with considerable increases in urinary adrenaline excretion. Noradrenaline, however, was raised only in the two elderly groups. All the subjects were considerably aroused by the test as judged by changes in the skin conductance, heart rate and electrocardiogram. The significance of decreased responsivity of the sympatho-adrenomedullary system to stressful situations in young women is discussed with reference to their low incidence of coronary artery disease.     

Compared effects of three dose-levels of ticlopidine on platelet function in normal subjects.

The compared inhibitory effects of three dose-levels of Ticlopidine (300, 600 and 750 mg/day) on platelet function have been studied in a placebo controlled study. Ticlopidine exerted several significant effects namely lengthening of bleeding time (300 mg/day), reduction of platelet retention on a glass-bead column (300 mg/day), reduction of the rate and the maximum extent of aggregation induced by ADP 2 μM (300 mg/day) and 5 μM (300 mg/day). The aggregating effects of ADP 5 μM were followed by subsequent deaggregation of which the rate was significantly increased after administration of the product (300 mg/day). Ticlopidine also significantly inhibited the release of serotonin (as measured by ¹⁴C-5-HT) occurring during ADP 5 μM induced aggregation (300 mg/day). Epinephrine-induced aggregation (5 μM) was inhibited by Ticlopidine, but this effect was apparent on the first wave of aggregation only after 750mg/day. On the other hand, the maximal rate and aggregation of the second wave of epinephrine-induced aggregation were significantly inhibited after the administration of the product (300mg/day). Ticlopidine abolished the release of ¹⁴C-5-HT induced by 5 μM epinephrine but it was not possible to evaluate this effect statistically. No obvious effect was evidenced on the parameters of collagen-induced aggregation except a slight inhibition on release of ¹⁴C-5-HT. The majority of the results demonstrate the effectiveness of Ticlopidine as an antiaggregant. Regression lines were determined to show the correlation between the administered dose and these inhibitory effects. Even the lowest dose of 300 mg/day, which produced a moderate increase in bleeding time, significantly inhibited most of the parameters studied.     

The trigemino-cervical reflex in normal subjects

There are only few reports on the trigemino-cervical reflex in humans and there is debate over the best method of reflex examination. The aim of this study was, comparing different methods, to provide a reproducible method for evaluating the trigemino-cervical reflex. The trigemino-cervical reflex was studied in 32 healthy volunteers. The stimulation was applied to the supraorbital, infraorbital or mental nerve. Recordings were performed bilaterally from the sternocleidomastoid and trapezius muscles at rest. The reflex was also examined during maximal voluntary contraction of the sternocleidomastoid muscle after supraorbital nerve stimulation. It presented as a two-component reflex if recorded from a tonically active muscle and as a one-component reflex if recorded from a relaxed muscle. The most reproducible reflex responses were obtained from the resting sternocleidomastoid muscle after stimulation of the supraorbital nerve. In conclusion, the trigemino-cervical reflex may be most easily obtained from the relaxed sternocleidomastoid muscle after supraorbital nerve stimulation.     

The prevalence of relative afferent pupillary defects in normal subjects.

BACKGROUND: Observational and pupillographic studies of small numbers of normal subjects have shown that a small (<0.3 log units) relative afferent pupil defect (RAPD) is present in a minority. We have extended the investigation of the prevalence of RAPD to a larger number of normal subjects. METHODS: A total of 102 subjects were examined by observation and pupillography. The swinging flashlight test was performed using neutral density filters for quantification. During the pupillographic procedure, light-emitting diodes were placed in front of each eye, alternately flashing for 2.5 seconds with a 0.5 second break. A binocular real-time pupillometer recorded the direct and consensual pupillary responses. After artefact detection and removal, the amplitudes of pupillary response were determined and plotted against stimulus intensity. The means of the direct and the consensual responses were used for automated calculation of RAPD. RESULTS: By observation, there was no RAPD in 87 (85%) subjects; there was an RAPD of 0.15 log units in 13 (13%), and an RAPD of 0.3 log units in 2 (2%). By pupillography, there was an RAPD of 0.07 log units in 53 (52%) subjects, an RAPD between 0.08 and 0.22 log units in 43 (42%) subjects, and an RAPD between 0.23 and 0.39 log units in 6 (6%) subjects. CONCLUSIONS: Observation and pupillographic measurements of the swinging light test in a large normal subject cohort has confirmed that an RAPD is present in a small minority but that it does not exceed 0.39 log units. The RAPD in these subjects may be explained by inaccuracy of measurement or by asymmetries in the connections between visual pathways and pretectal nuclei in the midbrain.     

The effects of age on a smooth pursuit tracking task in adults with schizophrenia and normal subjects.

BACKGROUND: Performance during a smooth pursuit eye movement (SPEM) task has been proposed as a marker of genetic risk for schizophrenia, although the precise component of SPEM tracking most associated with genetic risk remains undetermined. Normal adult aging is associated with deterioration on SPEM tasks; it remains unclear whether investigations of SPEM abnormalities will allow inclusion of older subjects in genetic studies. This study examines 1) the effect of normal aging on several components of SPEM performance; and 2) whether schizophrenic-normal differences found in young adults continue over a broad adult age span. METHODS: SPEM was recorded during a 16.7 degrees per sec constant velocity task in 64 normal adults, ages 18 to 79 years, and 58 schizophrenic subjects, ages 18 to 70 years. RESULTS: Smooth pursuit gain, the percent of total eye movements due to catch-up saccades, the frequency of large anticipatory saccades, and the frequency of leading saccades all deteriorate with increasing age. After correction for age, schizophrenic to control differences persist on most eye movement variables with the largest effect sizes for leading saccades (1.56) and smooth pursuit gain (1.17). CONCLUSIONS: The tendency to use saccades to anticipate target motion, even in small steps (leading saccades), deserves further attention as a potential marker useful in genetic analyses.     

The effects of exposure to moderate altitude on cardiovascular autonomic function in normal subjects

Cardiovascular responses to altitude have been studied on well-trained young subjects, generally at high altitudes (>4000 m). Less known are the effects of exposure to lower altitudes, easily reached by the general population. The aim of the study was to evaluate the effects of exposure to a moderate altitude (2950 m) on heart rate (HR), blood pressure (BP) profile, and cardiovascular autonomic function, and their correlation with hemoglobin oxygen saturation (HbO2S), in untrained subjects of a wide age range. Twenty-seven healthy normotensive subjects (age range 6–83; 8 children, 9 adults, and 10 elderly subjects) underwent a battery of noninvasive cardiovascular reflex tests and 24-h ambulatory BP monitoring. Corrected QT interval was also calculated. HbO₂S was measured with a transcutaneous oxymeter. All measurements were performed at about 200 m (s.l.) and repeated at 2950 m. 24-h HR and systolic/diastolic BP mean values increased at 2950 m in children (% change respectively: 6.4±6.4, p<0.05; 6.5±4.0/13.5±6.9, p<0.05), adults (4.9±8.1, NS; 6.0±5.1/8.1±5.8, p<0.05), and elderly subjects (7.2±4.8, p<0.05; 5.1±2.3/2.8±4.1, p<0.05 for systolic BP only). Standard deviation of BP mean values increased during night-time in the adult group (p<0.05). All subjects scored normal cardiovascular test results and no differences were observed after exposure to 2950m, at both 1 hour and 24 hours from arrival. After exposure to altitude, HbO₂S decreased significantly in the three groups, both on arrival and after 24 hours. No correlation was found between changes in HbO₂S and BP/HR responses, and cardiovascular test results. In conclusion, exposure to moderate altitudes, easily and often reached by the general population, causes a small but significant increase in BP and HR in healthy untrained subjects of a wide age range (6–83 years). Some physiological factors (eg, lower environmental temperature and lifestyle modification) together with hypoxia, possibly more than altered cardiovascular reactivity, seem responsible for this cardiovascular change. In terms of end-organ damage, the clinical relevance of this increase in BP and BP variability for repeated exposure is not known.     

Voluntarily simulated tremor in normal subjects.

Based on the hypothesis that rhythmical, tremor-like movements produced by normal subjects might be influenced by similar central oscillatory neuronal networks believed to determine the features of the pathologic tremors of Parkinson's disease (PD) or Essential Tremor (ET) patients, we examined the neurophysiological characteristics of a tremor mimicked by normal volunteers and compare this data with those from PD or ET tremors. Voluntarily simulated tremor (VST) was studied in 47 neurologically intact subjects, resting tremor in 10 patients with PD and postural tremor in 10 patients with ET. Using a tremor analysis system based on a solid state gyroscopic sensor sensitive to angular rate, the following parameters were determined: frequency, amplitude (angular displacement) and regularity (Q coefficient of constancy). We also performed an inertial loading test and a test-retest analysis. Nearly all normal subjects were able to simulate a tremor that was indistinguishable, in frequency and regularity, from that of PD or ET, although the amplitude was significantly higher in normal subjects. As in pathological tremors, the VST frequency was significantly influenced by age, but not by gender, handedness or previous knowledge of tremor. Inertial load did not modify the tremor frequency, suggesting that mechanical factors were minor. We also found a logarithmic inverse relationship between frequency and amplitude of the VST. We concluded that VST shares many similarities with pathological tremors. It is therefore possible that all tremors are somehow influenced by the same central oscillators which may become disinhibited and clinically apparent in pathological conditions such as PD or ET.     

Direct demonstration of long latency cortico-cortical inhibition in normal subjects and in a patient with vascular parkinsonism.

OBJECTIVE: The motor evoked potential to a single suprathreshold transcranial magnetic stimulus (TMS) is suppressed by a preceding stimulus given 100-200 ms before (long latency intracortical inhibition, LICI). The effect is enhanced in patients with Parkinson's disease. Although previous studies have agreed that the effect is cortical, there is disagreement over exactly which cortical mechanisms are involved. The aim of this study was to provide further evidence for cortical involvement in LICI. METHODS: Recordings of corticospinal volleys evoked by the TMS stimulation were made from electrodes inserted into the cervical epidural space of 4 conscious subjects. Three of the patients had received the electrodes for treatment of lumbo-sacral pain; the other patient had vascular parkinsonism, and had the electrode implanted to evaluate its effect on cerebral blood flow. The number and amplitude of the volleys were compared with and without a conditioning stimulus. RESULTS: In 3 pain patients, a conditioning stimulus suppressed the later components of the corticospinal volley (I2 and later waves) when the interval between stimuli was 100-150 ms; at 50 ms the responses were enhanced. Early components of the volley were not affected. Inhibition was much more pronounced and involved all descending volleys except the D wave in the patient with vascular parkinsonism. CONCLUSIONS: LICI, which is conventionally described in EMG recordings, is also evident in recordings of descending corticospinal volleys and appears enhanced in a patient with vascular parkinsonism.     

The median palmar cutaneous nerve in normal subjects and CTS.

OBJECTIVE: The neurophysiological confirmation of carpal tunnel syndrome (CTS) relies on detecting abnormal median nerve transcarpal conduction in the presence of unaffected comparator nerves. We compare the palmar cutaneous median branch (PCBm) with the ulnar sensory nerve conduction to digit 5 (US(5)) as comparator nerves for diagnosing CTS. METHODS: In a prospective case control study of patients with clinically defined carpal tunnel syndrome and normal subjects, we determined and compared the PCBm and US(5) conduction velocity. RESULTS: We examined 57 hands with clinically defined CTS and 59 control hands. Comparison showed highly significantly slowed PCBm conduction (p<0.0001) but not for US(5) conduction (p=0.488). Using a 3 percentile cut-off for abnormality derived from controls, PCBm conduction velocity was abnormal in 46% of CTS hands. CONCLUSIONS: The high frequency of PCBm nerve conduction abnormality in CTS suggests that this nerve should not be used as a comparator nerve for the neurophysiological diagnosis of CTS. This finding may help explain some of the extension of sensory symptoms outside the median nerve distribution in CTS. SIGNIFICANCE: In CTS frequent abnormality of PCBm conduction makes this a poor comparator nerve and may explain extension of sensory symptoms beyond the median nerve.     

Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.