Autonomic recovery following sprint interval exercise.

The autonomic nervous activity was assessed following supramaximal exercise through heart rate (HR) and blood pressure (BP) variability (HRV and BPV) and baroreflex sensitivity (BRS). The beat-to-beat HR and BP were recorded during the supine and standing states before (PRE) and at 60 (R60) and 120 min (R120) following single (one Wingate, 1W) and multiple sprint intervals (four Wingates interspersed with 4 min of light cycling, 4W). The supine low frequency (LF) component was increased (P<0.001) and the high frequency (HF) was reduced (P<0.01) at R60 (LF, 178.1 ± 11.0; HF, 74.8 ± 10.5) compared with PRE (LF, 140.2 ± 7.4; HF, 110.4 ± 7.2) after both exercises. Supine systolic BPV LF:HF was higher at R60 (4.6 ± 1.4) compared with PRE (6.8 ± 2.4) only after 4W (P=0.035). Supine BRS was lower (P<0.001) at R60 (6.8 ± 1.1) than at PRE (15.3 ± 1.8) and R120 (11.3 ± 1.3). BRS at R120 remained lower after 4W (P=0.02). Standing BRS was less (P<0.001) at R60 (2.3 ± 0.5) than at PRE (5.6 ± 0.8) or R120 (3.7 ± 0.6) and returned to PRE values only after 1W. We concluded that (a) autonomic balance is shifted to a greater sympathetic and less parasympathetic activation following both types of exercise, (b) it takes longer than 1 h to recover following supramaximal exercise and (c) the recovery is longer after 4W than 1W.

A comparison of autonomic function in patients with inflammatory bowel disease and in healthy controls.

We evaluated autonomic function, symptoms and psychological parameters in patients with ulcerative colitis (UC), Crohn's disease (CD) and matched controls to assess whether UC patients have greater basal sympathetic autonomic activity. Outpatients with UC (n = 15), CD (n = 13) and healthy controls (n = 28) underwent spectral analysis of heart rate variability to assess cardiac autonomic function, a methacholine challenge to assess cholinergic pulmonary responsiveness, and questionnaires assessing disease severity, anxiety and depression. UC but not CD patients had greater sympathetic activity than controls with increased absolute (6600 vs 5884; P = 0.04) and relative (62.8%vs 54.8%; P = 0.02) low frequency areas. This was not because of increased overall autonomic nervous system (ANS) activation and was independent of disease activity. In UC patients, trait (personality-related) anxiety correlated strongly with disease symptoms (R = 0.84; P < 0.001) and quality of life (R = -0.81; P < 0.001) while situational (state) anxiety did not. In CD patients, ANS measures were similar to controls and disease activity was unrelated to psychological measures. Cholinergic pulmonary responsiveness was normal in both UC and CD patients. UC patients have an increased sympathetic ANS activity which is independent of symptom severity. In these patients symptom severity is strongly associated with measures of personality related (but not current) anxiety.

The effect of sham feeding on neurocardiac regulation in healthy human volunteers.

BACKGROUND: Distension and electrical stimuli in the esophagus alter heart rate variability (HRV) consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific. OBJECTIVE: To test the hypothesis that sham feeding increases the high frequency (HF) component of HRV, indicating increased neurocardiac vagal activity in association with the known, vagally mediated, increase in gastric acid secretion. METHODS: Continuous electrocardiography recordings were obtained in 12 healthy, semirecumbent subjects during consecutive 45 min baseline, 20 min sham feeding (standard hamburger meal) and 45 min recovery periods. The R-R intervals and beat-to-beat heart rate signal were determined from digitized electrocardiography recordings; power spectra were computed from the heart rate signal to determine sympathetic (low frequency [LF]) and vagal (HF) components of HRV. RESULTS: Heart rate increased during sham feeding (median 70.8 beats/min, 95% CI 66.0 to 77.6; P<0.001), compared with baseline (63.6, 95% CI 60.8 to 70.0) and returned to baseline levels within 45 min. Sham feeding increased the LF to HF area ratio (median: 1.55, 95% C.I 1.28 to 1.77; P<0.021, compared with baseline (1.29, 95% CI 1.05 to 1.46); this increase in LF to HF area ratio was associated with a decrease in the HF component of HRV. CONCLUSIONS: Sham feeding produces a reversible increase in heart rate that is attributable to a decrease in neurocardiac parasympathetic activity despite its known ability to increase vagally mediated gastric acid secretion. These findings suggest that concurrent changes in cardiac and gastric function are modulated independently by vagal efferent fibres and that vagally mediated changes in organ function are stimulus- and organ-specific.

Neural regulation of heart rate variability in endurance athletes and sedentary controls.

OBJECTIVE: The aim was to examine the cardiac autonomic responses to orthostatic stress and recovery from steady state exercise in endurance trained athletes and sedentary subjects. METHODS: The power spectrum of heart rate variability was measured before and after exercise in 10 male long distance runners and 14 male sedentary control subjects. Both groups were comparable in sex, age, and body mass index. Continuous ECG recordings were obtained during the following physiological manoeuvres: 45 min supine rest state; 10 min standing; 15 min steady state exercise at 50% maximum workload, and 15 min while supine during post-exercise recovery. The resting heart rate of athletes was lower than controls, at 52(SD 4.9) v 67(8.7) beats.min-1, p < 0.001. Power spectrum analysis was performed using autoregressive modelling. RESULTS: The resting high frequency (HF) vagal component was higher in athletes than controls, at 62 (10.7) v 44(22.4) beats.min-1.Hz-1, p < 0.05. The resting low frequency (LF) peak power was significantly reduced in athletes, at 54(9.9) v 70(19.5) in control, p < 0.05. Although no group differences were observed during upright posture or exercise, the LF:HF area ratio had already returned to pre-exercise levels within 5 min of recovery in athletes. Conversely, it required up to 15 min of recovery before a noticeable decrease in the LF:HF area ratio was seen in controls. CONCLUSIONS: These data support the hypothesis that endurance training modifies heart rate control in whole or in part through neurocardiac mechanisms.

Neurocardiac and cerebral responses evoked by esophageal vago-afferent stimulation in humans: effect of varying intensities.

OBJECTIVE: This study was designed to determine whether esophageal vago-afferent electrostimulation, over a wide range of stimulus intensities, can sustain a cardiac vago-efferent effect by way of central nervous system processing. METHODS: Studies were performed in ten healthy male subjects (23.9 +/- 6.3 years). Esophageal electrostimulation was carried out using a stimulating electrode placed in the distal esophagus. Stimulation of esophageal vago-afferent fibres was employed using electrical impulses (200 microseconds at 0.2 Hz x 128 s) varying from 2.7 to 20 mA. Respiratory frequencies, beat-to-beat heart rate autospectra and cerebral evoked potentials were recorded at baseline and at each stimulus intensity in random order. RESULTS: With esophageal electrical stimulation, we observed a small non-significant decrease in heart rate. There was a dramatic shift of the instantaneous heart rate power spectra towards enhanced cardiac vagal modulation with intensities as low as 5 mA. This effect was sustained throughout all intensities with no further change in either the low frequency or high frequency power. Conversely, there was a linear dose response relationship between cerebral evoked potential amplitude and stimulus intensity mainly occurring above perception threshold (10 mA). Esophageal stimulation had no significant effect on heart rate or respiratory frequency at any stimulus intensity. CONCLUSIONS: These results indicate that electrical stimulation of the distal esophagus across a wide range of current intensities elicits a reproducible shift in the heart rate power spectrum towards enhanced vagal modulation. The data suggest a closed loop afferent/efferent circuitry wherein tonic visceral afferent impulses appear to elicit a phasic or modulatory vago-efferent cardiac response in healthy subjects.

Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction.

BACKGROUND: Brain serotonin is known to possess sympathoinhibitory properties. The aim of this clinical physiologic study was to determine whether sertraline, a selective serotonin reuptake inhibitor, facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infarction (MI) in patients with depression. METHODS AND RESULTS: Thirty-eight post-MI depressed patients were randomized to receive either sertraline 50 mg per day or placebo for 6 months. Depression was defined as a score >15 on the standardized Inventory to Diagnose Depression questionnaire taken at prehospital discharge and again within 2 weeks of the acute infarct. Eleven stable post-MI nondepressed patients served as a nonrandomized reference group during follow-up. Twenty-seven patients completed the randomization. All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability (HRV) indices at baseline (1-2 weeks after MI) and at 6, 10, 14, 18, and 22 weeks. The rate of recovery of HRV was determined by use of a growth curve model based on repeated-measures analysis of variance. There was a linear rate of increase in the SD of 24-hour N-N intervals (SDNN) in the sertraline-treated group that paralleled that of the nondepressed reference group. This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks (t = 2.10, P <.05). However, the short-term power spectral indices, while trending toward a more rapid rate of recovery in the treated group, did not reach statistical significance compared with the placebo group. CONCLUSION: In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN, a recognized predictor of clinical outcome.

Diurnal variations of neurocardiac rhythms in acute myocardial infarction.

To determine the diurnal pattern of cardiac autonomic tone in acute myocardial infarction (AMI), this study examined the power spectrum of heart rate (HR) variability in 24 patients during a single 24-hour segment within 4 days of AMI. Patients were nonrandomly allocated to a group (n = 14) without autonomic drugs and to a group (n = 10) already receiving beta blockers at the time of AMI. With use of autoregressive modeling, the power spectrum of HR variability was computed from continuous 1-hour electrocardiographic segments recorded at equally spaced intervals; 7 to 8 A.M., 3 to 4 P.M., and 11 to 12 P.M. All patients were supine, awake and pain free during recordings. There were no differences in HR, HR variance or the low-frequency peak power (0.06 to 0.1 Hz) from one temporal sequence to another. For the patients not taking beta blockers, the high-frequency peak power (0.2 to 0.36 Hz) or vagal component increased significantly from 3 P.M. to 11 P.M. (28 +/- 11 to 45 +/- 20 beats/min2.Hz-1, p less than 0.01). There was a significant decrease in the low- to high-frequency peak power and area ratios from 3 P.M. to 11 P.M. All power spectral parameters in the patients taking beta blockers remained unchanged over 24 hours. There was significantly heightened vagal modulation of sinus node activity in those receiving beta blockers, especially at 7 A.M. and 3 P.M. The data suggest that under steady-state wakeful conditions in the early recovery phase after an AMI, vagal tone is more pronounced during the late evening hours with a possible shift to relative sympathetic dominance during early morning and midafternoon hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Variable clinical expression of mosaic trisomy 16 in the newborn infant.

Trisomy 16 is common in embryos and fetuses aborted early during development. Mosaicism for trisomy 16 is sometimes encountered during prenatal diagnosis, particularly with chorionic villi biopsy specimens, and, until recently, was thought to be confined to the placenta. However, recently, several liveborn infants with trisomy 16 mosaicism have been described. We report on an additional liveborn infant with trisomy 16 mosaicism and compare the clinical findings with those of the previously reported cases in an attempt to delineate a mosaic trisomy 16 syndrome. Cytogenetic analysis from our patient showed that there was a different proportion of abnormal cells in different tissues and that the anomaly was undetectable in blood lymphocyte cultures. This observation was consistent with some of the previous reports. DNA analysis of parents and child was carried out using a polymorphic dinucleotide marker that maps to the long arm of chromosome 16. This analysis showed that the extra chromosome 16 in the infant was maternal in origin and suggested that the nondisjunction was probably a first meiotic division error. Our results suggest that an investigation of multiple tissues is required before concluding that mosaicism is confined to the placenta. We conclude that a finding of trisomy 16 mosaicism at prenatal diagnosis should be regarded with extreme caution. This diagnosis may be associated with a highly variable phenotype that may occasionally be compatible with extrauterine life.

Cardiac autonomic dysfunction in survivors of acute lymphoblastic leukemia in childhood.

The purpose of this study was to investigate autonomic regulation of neurocardiac function in survivors of acute lymphoblastic leukemia (ALL) in childhood, through power spectral and time domain analyses of the heart rate variability signal. Studies were conducted on 34 unselected patients and 34 age matched controls. Patients were in remission, off therapy for at least 20 months and from high risk (HR, n=21) and standard risk (SR, n=13) groups as described by Dana-Farber Cancer Institute protocols 87-01 and 91-01. Twenty-nine patients had received cranial irradiation, 7 on a hyperfractionated schedule. Power spectral analysis of the heart rate (PS/HRV) was performed on 30 min heart rate time series and time domain statistics were computed from 24 h Holter recordings. Left ventricular function was assessed by measuring ejection and shortening fractions on echocardiography. All such measures were normal. Analysis of PS/HRV revealed that the supine low frequency: high frequency (LF:HF) area ratio was elevated in patients compared to controls. Changes in the LF and HF power on standing were attenuated in the patients compared to controls. Circadian analysis revealed a depressed diurnal rhythm of heart rate in the patients. Those from the SR group showed greater reduction of the LF power response to orthostatic stress and a reduced circadian rhythm of the heart rate compared to those with HR ALL. Patients from the HR group showed reductions in both HF and LF power responses to orthostasis compared to controls. Elevated supine LF power and depressed circadian variation in the HF power band were evident only in female subjects. Patients who received standard cranial irradiation had higher LF:HF area ratio and diminished LF and HF power responses to orthostatic stress than did subjects in the hyperfractionated group. These findings suggest that the autonomic nervous regulation of the heart is compromised in patients treated for ALL in childhood even when resting echocardiographic measures provide no evidence of cardiac decompensation. The extent of neurocardiac dysfunction is influenced by risk status, gender and schedule of cranial irradiation.

Disc immobilization of Björk-Shiley and Medtronic Hall valves during and immediately after valve replacement.

During the last fourteen years, 377 unileaflet tilting-disc prosthetic valves (Björk-Shiley and Medtronic Hall) have been used for single or multiple valve replacements with and without concomitant coronary artery by-pass grafting. In the past five years, five instances of disc immobilization (three in the mitral and two in the aortic position) occurred either at the time of weaning from cardiopulmonary bypass or immediately thereafter. When the implanted site of the prosthetic valve was the mitral position, reexploration in 2 patients revealed chordal remnants in the subannular area stuck between the disc occluder and the valve ring, thereby immobilizing the disc. In the third instance, the free movement of the disc was impeded by the left ventricular myocardium. In the aortic position, an unraveled suture impacted between the disc occluder and the valve ring immobilized the disc in 1 patient. In the other patient, the cause of the malfunction could not be determined at the time of reexploration. The 1 death among these 5 patients was directly related to the malfunction of the prosthesis. The mechanism, recognition, treatment, and prevention of this catastrophic malfunction of tilting-disc valves are discussed.

Esophageal mucocele: a complication of blind loop esophagus.

Mucocele of the bypassed esophagus is an unusual complication of esophageal replacement and has been described only in isolated references. This report is based on our experience with 6 patients in whom a mucocele developed following esophageal replacement. Esophageal replacement was performed on 37 patients over a 10-year period at the Medical College of Georgia Hospital. A symptomatic mucocele requiring excision developed in 3 patients with achalasia, 1 with congenital tracheoesophageal fistula, 1 with esophageal atresia, and 1 with inflammatory stricture. Conduits used included stomach (4), reversed gastric tube (1), and colon (1). Our experience indicates that conversion of a closed-loop esophagus into a symptomatic mucocele is more likely in the presence of functioning, chronically irritated mucosa. The clinical features were referable to the mucocele itself or respiratory embarrassment therefrom. Thoracic roentgenograms and computed tomographic scans were diagnostic in verifying the presence of the esophageal mucocele. All five mucoceles arose from squamous epithelium. One of 3 patients with achalasia in whom a mucocele developed following esophageal replacement had premalignant changes in the mucosa. Based on this experience, our treatment of choice is early, complete excision of the mucocele.

The cerebral response to electrical stimuli in the oesophagus is altered by increasing stimulus frequencies.

Recording of cerebral evoked responses (EP) allows the assessment of visceral afferent pathways and gut-brain communication, but the optimal stimulation parameters remain to be established. The present study determined the optimal stimulation frequency of electrical stimulation of the oesophagus to elicit EP responses. In 13 healthy male volunteers (24.1 +/- 5.9 years), a 5 mm stainless-steel electrode was placed in the distal oesophagus for electrical stimulation (ES). EP were recorded from 21 scalp electrodes placed according to the 10/20 International system. ES (15 mA, 200 microseconds) were delivered in repeated series of 24 stimuli. Stimulus frequency was randomly altered in different series using a pseudologarithmic range (0.1, 0.2, 0.3, 0.5, and 1 Hz). Two series of stimuli were applied using each stimulation frequency. Two-dimensional topographic brain maps were created using interpolation techniques at each stimulation frequency. With increasing stimulus frequency, a significant and progressive decrease of EP amplitudes was observed between frequencies of 0.1 Hz and 1.0 Hz (P1/N2: 7.6 +/- 1.2 vs 1.4 +/- 0.3* microV, N2/P2: 17.2 +/- 1.7 vs 4.6 +/- 0.4* microV, P2/N3: 6.9 +/- 0.7 vs 4.2 +/- 0.5* microV; * = P < 0.05). In addition, there was a significant shortening of the mean peak latency of the intercalated P2 peak (P < 0.0005), with a similar trend for the P3 peak (P < 0.06), with increasing stimulus frequency from 0.1-1.0 Hz. Topographic brain maps localized the maximal early peaks (N1,P1.N2) in the paracentral cortical region (C3, Cz, C4), whereas the later peaks (P2 to P3) were symmetrically spread over the centroparietal and temporal regions (Cz, Pz, T5, T4). There was no difference in the cortical location of maximal EP amplitudes with increasing stimulus frequency. In conclusion, there is a clear relationship between stimulus frequency and amplitude of EP, suggesting rapid attenuation of the cerebral autonomic neural responses with increased electrical stimulation frequency. The effect of increased frequency on peak latencies suggests an alteration of stimulus processing in the thalamocortical region due to an altered perception of stimuli. Early EP peaks originate from basal structures of primarily the dominant hemisphere, while later peaks are localized in centroparietal cortical regions.

Cognitive evoked potentials to anticipated oesophageal stimulus in humans: quantitative assessment of the cognitive aspects of visceral perception.

Evoked potential studies provide an objective measure of the neural pathways involved with perception. The effects of cognitive factors, such as anticipation or awareness, on evoked potentials are not known. The aim was to compare the evoked potential response to oesophageal stimulation with the cortical activity associated with anticipation of the same stimulus. In 12 healthy men (23.5 +/- 4 years), oesophageal electrical stimulation (15 mA, 0.2 Hz, 0.2 msec) was applied, and the evoked potentials recorded using scalp electrodes. A computerized model of randomly skipped stimuli (4:1 ratio) was used to separately record the evoked potentials associated with stimulation and those associated with an anticipated stimulus. The electrical stimulus represented the nontarget stimulus and the skipped impulse the target (anticipatory) stimulus. This anticipatory evoked potential was also compared to auditory P300 evoked potentials. Reproducible evoked potentials and auditory P300 responses were elicited in all subjects. Anticipatory evoked potentials (peak latency 282.1 +/- 7.9 msec, amplitude 8.2 +/- 0.7 microV, P < 0.05 vs auditory P300 evoked potential) were obtained with the skipped stimulus. This anticipatory evoked potential was located frontocentrally, while the auditory P300 potential was located in the centro-parietal cortex. The anticipatory evoked potential associated with expectation of an oesophageal stimulus, although of similar latency to that of the auditory P300 evoked response, originates from a different cortical location. The recording of cognitive evoked potentials to an expected oesophageal stimulus depends on attention to, and awareness of, the actual stimulus. Anticipatory evoked potentials to GI stimuli may provide an objective electrophysiological tool for the assessment of the cognitive factors associated with visceral perception.

Abnormal cerebral processing of oesophageal stimuli in patients with noncardiac chest pain (NCCP).

In noncardiac chest pain (NCCP), altered visceral perception may result from abnormal cerebral processing of sensory input rather than abnormalities of afferent pathways. However, the interactions between symptoms, autonomic function and oesophageal stimuli are poorly studied. Oesophageal stimulation elicits reproducible cortical evoked potentials [CEP] and modulates heart rate variability via vagal pathways, as visible on power spectrum analysis of heart rate variability [PS-HRV]. These methods are increasingly used to study the function of visceral afferent neural pathways in human. The aim of this study was to compare EP and PS-HRV during oesophageal stimuli in NCCP and controls. Twelve healthy volunteers (one female, 11 male; aged 24-51 years; mean 32 +/- 8 years), and eight NCCP patients (three female, five male; age range 26-58, mean 40.5 +/- 10 years) were studied. Electrical oesophageal stimulation (EOS; 200 microseconds, 0.2 Hz, 25 stimuli) was applied to the oesophageal wall 5 cm above the lower oesophageal sphincter (LOS), and perception thresholds (measured in mA) determined. EP responses were recorded using 22 standard electroencephalogram scalp electrodes. Autonomic activity was assessed using PS-HRV, before, during, and after oesophageal stimulation. Measured PS-HRV indices included high frequency (HF; 0. 15-0.5 Hz) and low frequency (LF; 0.06-0.15 Hz) power, respectively, assessing vagal and sympathetic activity, and the LF/HF ratio. EOS perception occurred at lower thresholds in NCCP than in controls (3. 6 +/- 1 vs. 7.8 +/- 2 mA, P < 0.05). EP amplitude was greater (13 +/- 2 vs. 6 +/- 1 microV, P < 0.0001), and latency longer in controls vs. NCCP (191 +/- 7 ms vs. 219 +/- 6 ms, P < 0.001). In NCCP, EOS decreased sympathetic outflow (low frequency peak on PS-HRV) and increased cardiovagal activity (high frequency peak, P < 0.02) to a significantly higher degree in comparison with controls. During EOS, heart rate decreased in NCCP from 68 vs. 62 beats min-1 (P < 0.003) but not in controls. In NCCP patients, EOS was perceived at lower intensities and was associated with a greater cardiovagal reflex response. EP responses associated with EOS were smaller in NCCP than in controls, suggesting that an increased perception of oesophageal stimuli results from an enhanced cerebral processing of visceral sensory input in NCCP, rather than from hyperalgesic responses in visceral afferent pathways.

Double blind placebo controlled trial of short term transdermal scopolamine on heart rate variability in patients with chronic heart failure.

OBJECTIVE: To test the hypothesis that short term application of transdermal scopolamine increases heart rate variability (HRV) and restores sympathovagal balance in patients with stable congestive heart failure (CHF). DESIGN: A double blind placebo controlled crossover study. SETTING: Tertiary referral centre. PATIENTS: Twelve patients (mean age 66 (10)) with New York Heart Association class II-IV CHF. All patients had coronary artery disease (mean left ventricular ejection fraction 26.7 (8.9) %). INTERVENTION: Patients were randomly assigned to receive either a placebo skin patch or a transdermal scopolamine patch (Transderm, 0.05 mg/h). Patches remained in place for 48 hours with a 24 hour washout period before crossover. OUTCOME MEASURES: HRV was derived from (a) 24 hour time domain indices (mean RR interval, standard deviation of interbeat interval, and the baseline width of the frequency distribution of RR intervals) and (b) short data set (2.2 mm) power spectral measurements using autoregressive modelling. Autospectral measures were performed in both resting supine and standing (orthostatic) states. The 24 hour Holter record was obtained during the second day of patch application. RESULTS: There was a small but significant (P < 0.05) increase in all time domain HRV variables with scopolamine. There was a paradoxical fall in low frequency (LF) spectral power induced by orthostasis during baseline (-30%) and placebo (-34%) states. Conversely, scopolamine was associated with a 14% increase in LF power during orthostatic stress. Scopolamine thus significantly reduced the orthostatic fall in LF (P < 0.01) compared with either baseline or placebo values. No difference in circadian rhythm was seen between the scopolamine and placebo treatment periods. However, the abrupt fall in the high frequency (vagal) power during the early morning sleep-wake hours was reduced by scopolamine. Scopolamine was also associated with a significant rightward shift in the resting LF central frequency consistent with a vagomimetic effect. CONCLUSION: Patients with chronic stable CHF showed a paradoxical fall in the low frequency (sympathetic) power during orthostatic stress. Transdermal scopolamine applied over a 48 hour period partially restored the balance between sympathetic tone and vagal activity in CHF patients and maintained this balance during orthostatic stress.

Regional distribution and kinetics of [18F]6-flurodopamine as a measure of cardiac sympathetic activity in humans.

OBJECTIVES: To determine whether an increase in cardiac sympathetic activity produced by exercise or sublingual glyceryl trinitrate causes an increased rate of loss of fluorine-18 from the myocardium after intravenous [18F]6-fluorodopamine ([18F]F-DA) in normal volunteers. In addition, to determine the contribution of non-specific uptake of [18F]F-DA in the myocardium in patients with recent heart transplant. PROTOCOL: [18F]F was prepared by direct electrophilic fluorination of dopamine. Nine healthy volunteers each received 1.85 x 10(8) Bq (168-250 micrograms) [18F]F-DA over a period of 3 min and were scanned for 2 h in an ECAT 953/31 tomograph. Three controls were scanned before and after vigorous cycle exercise and two were scanned before and after sublingual glyceryl trinitrate. In addition, two patients (1 and 2 years post-heart transplant) underwent a myocardial perfusion study with ammonia labelled with nitrogen-13 followed by an [18F]F-DA study. RESULTS: There was intense uniform uptake of [18F]F-DA throughout the myocardium in the healthy volunteers. The time course of 18F in the myocardium under resting conditions fitted a biexponential function with mean half-times of 8.0 and 109 min. Vigorous exercise produced a three to fivefold increase in the rate of loss of 18F compared with that when resting. After glyceryl trinitrate, one control had a profound reduction in blood pressure (23%) and twofold increase in the rate of loss of myocardial 18F. The other control had no physiologically significant change in blood pressure, heart rate, or rate of loss of myocardial 18F. Uptake of [18F]F-DA in the two posttransplant patients was confined to a small anterobasal region adjacent to the atrioventricular groove, while blood flow, as measured with [13N] ammonia, was uniformly distributed throughout the myocardium. Partial reinnervation of the myocardium was confirmed by the presence of distinct low frequency spectral peaks of the heart rate power spectrum in both patients. CONCLUSIONS: These results suggest that the uptake of [18F]F-DA reflects the distribution of cardiac sympathetic innervation and that the rate of loss of 18F from the myocardium partially reflects spill over of noradrenaline. The technique may be useful in investigating various cardiac conditions in which the sympathetic system is compromised.

Power spectral analysis of heart rate variability: a noninvasive signature of cardiac autonomic function.

Power spectral analysis of short segments of beat-to-beat heart rate variability (PS/HRV) reveals three distinct peaks. In human PS/HRV, the high frequency (HF) band (0.15 to 0.4 Hz) is correlated with respiratory driven vagal efferent input to the sinus node. The low frequency band (LF) 0.06 to 0.15 Hz is believed to be due to baroreceptor mediated blood pressure control. Therefore, PS/HRV represents a noninvasive signature of the balance between sympathetic and parasympathetic components of the autonomic nervous system. This paper reviews the literature on the methodological issues relevant to signal processing, computational, and clinical applications of PS/HRV. Factors affecting the power in the LF and HF bands are examined in healthy controls. Recent work from several laboratories suggests that PS/HRV is a potentially powerful tool for exploring neurocardiac dysfunction in patients with a variety of cardiac and autonomic disorders. Mathematical models which simulate neurocardiac control are examined. Concerns regarding the lack of standardization between different laboratories are expressed. As the PS/HRV attains the status of a clinical diagnostic test, we hope that this review serves as a source of integrated information for researchers in this field.

Cerebral evoked responses to gastrointestinal stimulation in humans.

Recent advances have permitted recording of evoked potentials (EPs) in response to electrical and mechanical stimulation of the gastrointestinal (GI) organs via methods used primarily in clinical neurophysiology. Current research involving stimulation of the esophagus, rectum, and colon, and recording the corresponding responses on the scalp, is being practiced in only a few laboratories. This review examines the engineering aspects of recording EPs, such as characteristics of the stimuli, placement of stimulus electrodes in the GI tract, and enhancement of evoked potential signals. We also discuss the physiological concepts involved in the generation of EPs, and how these compare with somatosensory evoked responses. Current experimental techniques employed by various investigators and results reported from their laboratories are compared. We believe that cerebral EPs to GI stimulation could be useful in studying a number of pathophysiological conditions such as gastroesophageal reflux disease, diffuse esophageal spasm, chronic inflammatory bowel disorders, chronic abdominal pain, and irritable bowel syndrome, among others. We hope that the present review will generate interest in the use of EPs arising out of GI stimulation, aiding in understanding their physiological implications in healthy subjects and in GI disorders.

Effects of esophageal stimulation in healthy subjects.

We studied the effects of esophageal electrical stimulation on heart rate variability power spectra (PS/HRV) and cortical evoked potentials (EPs) in healthy subjects. The intensity of stimulation was varied from 2.7 to 20 mA. We found that the amplitude of the cortical evoked potentials (amplitude of the N2/P2 peak) increased from 5.1 +/- 0.7 microV at 5 mA to 16.3 +/- 1.1 microV at 20 mA. The PS/HRV showed an increase in the vagal modulation of the sinus node. When the stimulation frequency was varied from 0.1 to 1 Hz at a constant intensity of 15 mA, the amplitude of cortical EPs (N2/P2 peak) decreased with increase in the frequency of stimulation (p < 0.05). The LF:HF ratio decreased significantly for all frequencies of stimulation (p < 0.005). An experimental paradigm to evoke the cognitive component in the cortical EPs yielded a peak around 354 ms following the stimulus.

Effects of esophageal stimulation in patients with functional disorders of the gastrointestinal tract.

We studied the effects of esophageal electrical stimulation on cortical-evoked potentials (EPs) and power spectrum of heart rate variability (PS/HRV) in patients with diabetes and non-cardiac chest pain (NCCP). We also recorded cognitive-evoked potentials (P300 EPs) in response to an odd-ball stimulation in patients with NCCP. Diabetic patients did not yield reproducible cortical EPs. Their power spectra of heart rate variability (PS/HRV) showed an increased vagal modulation during stimulation. In patients with NCCP the P300 EPs were of greater amplitude (17 +/- 3 microV vs. 12 +/- 1 microV in controls, p < 0.04), while peak latencies were slightly elongated in patients (382 +/- 22 ms vs. 354 +/- 12 ms in controls). The PS/HRV in these patients also showed an increased vagal modulation of the sinus node activity. Our results suggest the following: (1) in patients with diabetes, afferent pathways and processing of sensory signals are likely to be impaired; (2) an increased perception of esophageal stimulation reflects an exaggerated brainstem response and altered cortical processing of visceral sensation in patients with NCCP.