Bitters: Time for a New Paradigm.

In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.

Bitter tastants alter gastric-phase postprandial haemodynamics.

ETHNOPHARMACOLOGICAL RELEVANCE: Since Greco-Roman times bitter tastants have been used in Europe to treat digestive disorders, yet no pharmacological mechanism has been identified which can account for this practice. This study investigates whether the bitter tastants, gentian root (Gentian lutea L.) and wormwood herb (Artemisia absinthium L.), stimulate cephalic and/or gut receptors to alter postprandial haemodynamics during the gastric-phase of digestion. MATERIALS AND METHODS: Normal participants ingested (1) 100 mL water plus capsules containing either cellulose (placebo-control) or 1000 mg of each tastant (n=14); or (2) 100mL of water flavoured with 500 or 1500 mg of each tastant (a) gentian (n=12) and (b) wormwood (n=12). A single beat-to-beat cardiovascular recording was obtained for the entire session. Pre/post-ingestion contrasts with the control were analysed for (1) the encapsulated tastants, in the "10 to 15" minute post-ingestion period, and (2) the flavoured water in the "5 to 10" minute post-ingestion period. RESULTS: Water, the placebo-control, increased cardiac contraction force and blood pressure notwithstanding heart rate decreases. Encapsulated tastants did not further alter postprandial haemodynamics. In contrast gentian (500 and 1500 mg) and wormwood (1500 mg) flavoured water elicited increased peripheral vascular resistance and decreased cardiac output, primarily by reducing stroke volume rather than heart rate. CONCLUSIONS: Drinking 100mL water elicits a pressor effect during the gastric-phase of digestion due to increased cardiac contraction force. The addition of bitter tastants to water elicits an additional and parallel pressor effect due to increased peripheral vascular resistance; yet the extent of the post-prandial blood pressure increases are unchanged, presumably due to baroreflex buffering. The vascular response elicited by bitter tastants can be categorised as a sympathetically-mediated cephalic-phase response. A possible mechanism by which bitter tastants could positively influence digestion is altering gastric-phase postprandial haemodynamics and supporting postprandial hyperaemia.

Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.

Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs) and so has the potential to elicit reflex autonomic responses. Coffee containing 130 mg caffeine has been reported to increase heart rate for 30 min post-ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion. This study aimed to clarify caffeine's chemosensory impact. Double-espresso coffees were compared to a placebo-control capsule in a double-blind between-measures design. Coffees tested were regular coffee (130 mg caffeine) and decaffeinated coffee with added-caffeine (0, 67 and 134 mg). Cardiovascular measures from three post-ingestion phases: 1) 0 to 5; 2) 10 to 15; and 3) 25 to 30 min; were compared to pre-ingestion measures. Participants comprised 11 women in the control group and 10 women in the test group. Decaffeinated coffee elicited no changes. Decaffeinated coffee with 67 mg caffeine: decreased dp/dt in Phase 1. Decaffeinated coffee with 134 mg caffeine: increased heart rate in Phases 1 and 2; decreased spontaneous baroreflex sensitivity in Phase 1; and increased diastolic pressure in Phases 2 and 3. Regular coffee: increased heart rate in Phases 1 and 2; decreased dp/dt in all phases; and decreased systolic pressure in Phase 1. Caffeine is the substance in regular coffee which elicits chemosensory autonomic reflex responses, which involves heart activity and the baroreflex. Compared to the caffeine in regular coffee, added-caffeine elicits somewhat different chemosensory responses including a more pronounced pressor effect and resetting of the baroreflex. Caffeine in commonly consumed amounts, as well as modulating body processes by blocking adenosine receptors, can elicit reflex autonomic responses during the ingestion of caffeinated drinks. It is plausible that caffeine stimulates hTAS2Rs, during the ingestion of coffee, eliciting cephalic phase responses. These cephalic phase responses likely result from vagal withdrawal and it is uncertain whether they enhance digestion or not.

Respiratory and non-respiratory sinus arrhythmia: implications for heart rate variability.

The quantity of blood arriving at the left side of the heart oscillates throughout the breathing cycle due to the mechanics of breathing. Neurally regulated fluctuations in the length of the heart period act to dampen oscillations of the left ventricular stroke volume entering the aorta. We have reported that stroke volume oscillations but not spectral frequency variability stroke volume measures can be used to estimate the breathing frequency. This study investigated with the same recordings whether heart period oscillations or spectral heart rate variability measures could function as estimators of breathing frequency. Continuous 270 s cardiovascular recordings were obtained from 22 healthy adult volunteers in the supine and upright postures. Breathing was recorded simultaneously. Breathing frequency and heart period oscillation frequency were calculated manually, while heart rate variability spectral maximums were obtained using heart rate variability software. These estimates were compared to the breathing frequency using the Bland-Altman agreement procedure. Estimates were required to be < ±10% (95% levels of agreement). The 95% levels of agreement measures for the heart period oscillation frequency (supine: -27.7 to 52.0%, upright: -37.8 to 45.9%) and the heart rate variability spectral maximum estimates (supine: -48.7 to 26.5% and -56.4 to 62.7%, upright: -37.8 to 39.3%) exceeded 10%. Multiple heart period oscillations were observed to occur during breathing cycles. Both respiratory and non-respiratory sinus arrhythmia was observed amongst healthy adults. This observation at least partly explains why heart period parameters and heart rate variability parameters are not reliable estimators of breathing frequency. In determining the validity of spectral heart rate variability measurements we suggest that it is the position of the spectral peaks and not the breathing frequency that should be the basis of decision making.

The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity.

UNLABELLED: The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity. INTRODUCTION: Caffeine is detected by 5 of the 25 gustatory bitter taste receptors (hTAS2Rs) as well as by intestinal STC-1 cell lines. Thus there is a possibility that caffeine may elicit reflex autonomic responses via chemosensory stimulation. METHODS: The cardiovascular impacts of double-espresso coffee, regular (130 mg caffeine) and decaffeinated, and encapsulated caffeine (134 mg) were compared with a placebo-control capsule. Measures of four post-ingestion phases were extracted from a continuous recording of cardiovascular parameters and contrasted with pre-ingestion measures. Participants (12 women) were seated in all but the last phase when they were standing. RESULTS: Both coffees increased heart rate immediately after ingestion by decreasing both the diastolic interval and ejection time. The increases in heart rate following the ingestion of regular coffee extended for 30 min. Encapsulated caffeine decreased arterial compliance and increased diastolic pressure when present in the gut and later in the standing posture. DISCUSSION: These divergent findings indicate that during ingestion the caffeine in coffee can elicit autonomic arousal via the chemosensory stimulation of the gustatory receptors which extends for at least 30 min. In contrast, encapsulated caffeine can stimulate gastrointestinal receptors and elicit vascular responses involving digestion. CONCLUSION: Research findings on caffeine are not directly applicable to coffee and vice versa. The increase of heart rate resulting from coffee drinking is a plausible pharmacological explanation for the observation that coffee increases risk for coronary heart disease in the hour after ingestion.

Habitual coffee and tea drinkers experienced increases in blood pressure after consuming low to moderate doses of caffeine; these increases were larger upright than in the supine posture.

Caffeine users have been encouraged to consume caffeine regularly to maintain their caffeine tolerance and so avoid caffeine's acute pressor effects. In controlled conditions complete caffeine tolerance to intervention doses of 250 mg develops rapidly following several days of caffeine ingestion, nevertheless, complete tolerance is not evident for lower intervention doses. Similarly complete caffeine tolerance to 250 mg intervention doses has been demonstrated in habitual coffee and tea drinkers' but for lower intervention doses complete tolerance is not evident. This study investigated a group of habitual caffeine users following their self-determined consumption pattern involving two to six servings daily. Cardiovascular responses following the ingestion of low to moderate amounts caffeine (67, 133 and 200 mg) were compared with placebo in a double-blind, randomised design without caffeine abstinence. Pre-intervention and post-intervention (30 and 60 min) 90 s continuous cardiovascular recordings were obtained with the Finometer in both the supine and upright postures. Participants were 12 healthy habitual coffee and tea drinkers (10 female, mean age 36). Doses of 67 and 133 mg increased systolic pressure in both postures while in the upright posture diastolic pressure and aortic impedance increased while arterial compliance decreased. These vascular changes were larger upright than supine for 133 mg caffeine. Additionally 67 mg caffeine increased dp/dt and indexed peripheral resistance in the upright posture. For 200 mg caffeine there was complete caffeine tolerance. Cardiovascular responses to caffeine appear to be associated with the size of the intervention dose. Habitual tea and coffee drinking does not generate complete tolerance to caffeine as has been previously suggested. Both the type and the extent of caffeine induced cardiovascular changes were influenced by posture.

The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine breathing frequency.

OBJECTIVE: The Finometer records the beat-to-beat finger pulse contour and has been recommended for research studies assessing short-term changes of blood pressure and its variability. Variability measured in the frequency domain using spectral analysis requires the impact of breathing be restricted to high frequency spectra (>0.15 Hz) so that the data from participants need to be excluded when the breathing impact occurs in the low frequency spectra (0.04-0.15 Hz). This study tested whether breathing frequency can be estimated from standard Finometer recordings using either stroke volume oscillation frequency or spectral stroke volume variability maximum scores. METHODS: Twenty-two healthy volunteers were tested for 270 s in the supine and upright positions. Finometer recorded the finger pulse contour and a respiratory transducer recorded breathing. Stoke volume oscillation frequency was calculated manually whereas the stroke volume spectral maximums were obtained using the software Cardiovascular Parameter Analysis. These estimates were compared with the breathing frequency using the Bland-Altman procedures. RESULTS: Stroke volume oscillation frequency estimated breathing frequency to less than +/-10% and 95% levels of agreement in both supine (-7.7 to 7.0%) and upright (-6.7 to 5.4%) postures. Stroke volume variability maximum scores did not accurately estimate breathing frequency. CONCLUSION: Breathing frequency can be accurately derived from standard Finometer recordings using stroke volume oscillations for healthy individuals in both supine and upright postures. The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine the breathing frequency.

Monitoring visual function in children with syndromic craniosynostosis: a comparison of 3 methods.

OBJECTIVE: To compare visual acuity, optic disc appearance, and transient pattern reversal visual evoked potentials as markers of possible visual dysfunction in children with syndromic craniosynostosis. METHODS: Serial visual acuity, optic disc appearance, and pattern reversal visual evoked potential data were recorded in 8 patients with syndromic craniosynostosis before and after cranial vault expansion. The pattern reversal visual evoked potentials were analyzed using linear regression modeling, applied to the N80 to P100 amplitude. RESULTS: Serial optic disc appearances were available for all 8 patients and visual acuities for 7 patients. The visual acuity deteriorated in only 1 patient, improved in 4, and fluctuated in 2, before surgery. Of the 8 patients, 3 showed no papilledema in either eye at any time, 3 showed progressive bilateral swelling before surgery, and 2 exhibited only unilateral disc swelling. In all 8 patients, there was a trend for the N80 to P100 amplitude to decrease before surgery and to increase, in all but 2 patients, after surgery. CONCLUSIONS: This study suggests that neither optic disc appearance nor visual acuity assessment alone is a reliable marker of potential visual dysfunction in children with syndromic craniosynostosis. It also suggests that the pattern reversal visual evoked potential can provide early evidence of visual dysfunction before vault expansion surgery in these children; this dysfunction may recover postoperatively.

Event-related potentials in pediatric cochlear implant patients.

OBJECTIVE: The main objective of this study was to assess the correlation of auditory event related potential (ERP) measures with behavioral assessment data to identify if ERPs including mismatch negativity (MMN) can be used to categorize cochlear implant patients into good and poor performers. DESIGN: We investigated auditory event-related potentials to standard and deviant speech stimuli presented in a pseudorandom sequence in 35 cochlear implant patients between the ages of 7 and 17 yr. We compared the occurrence, latencies, and amplitudes of P1, N2, and MMN with overall behavioral outcome in these children. Behavioral measures included category of auditory performance scores and speech intelligibility rating scores. RESULTS: Auditory ERPs in response to standard stimuli were identifiable in 30 of 35 patients, demonstrating a major positive component (P1) followed by a negativity (N2) with absence of N1 in all patients. The P1 component in prelingually deaf patients showed a statistically significant reduction in its latency with increasing duration of implant use. MMN was recorded in 80-85% of star performers but in only 15-20% of poor performers. Patients with higher SIR scores demonstrated statistically significant longer duration of MMN compared with those with a lower SIR score. CONCLUSIONS: These results indicate that MMN can be used to assess the functional status of the auditory cortex in terms of auditory memory and discrimination in young children with cochlear implants and may provide an objective mechanism for differentiating good from poor performers.

Speech and non-speech processing in hemispherectomised children: an event-related potential study.

Although hemispherectomy is now used as a radical treatment for intractable seizures in a number of centres, there have been limited electrophysiological studies investigating post-procedure auditory-speech processing and recovery or reorganisation. We therefore recorded auditory event-related potentials (ERPs) evoked by pure tones and syllables employing a 51-channel electrode array concentrated over the functional hemisphere in 17 patients (nine males, mean age 14.2 years) who had undergone hemispherectomy for intractable seizures; eight of the patients had congenital brain damage and nine had sustained their initial insult at an age of 1 year or older. For comparison, recordings were made from 10 controls (five males, mean age 13.5 years). Responses from patients consisted of five small amplitude components restricted to the functional hemisphere whose scalp polarity was opposite to the ERPs observed in control subjects. The topography of the auditory ERPs in the patients was localised to the centro-temporal regions of the functional hemisphere in comparison to the midline distribution observed in control subjects. As in the control subjects, the latencies of the components evoked by tones were shorter than those evoked by syllables in both left and right hemispherectomised children. In addition, further analysis of the N1 and P2 component revealed increased syllable latencies in left hemispherectomised children only. The results of this study suggest that the left hemisphere alone may be more efficient at processing both pure tones and syllables compared to the right or both together.

Functional outcome following stroke in children.

The aim of this study was to describe the functional consequences of childhood stroke in terms of activity limitation and to explore the relationship between extent of brain damage, impairment, and functional sequelae. A further aim was to describe the health of the parents of these children. Seventeen children and adolescents with cerebral infarction in the territory of the middle cerebral artery were enrolled in the study. A new activity limitation measure with a 4-point Likert scale (the Paediatric Stroke Activity Limitation Measure) was designed to examine the degree of difficulty experienced by the children in daily activities. The relationship between activity limitation scores, standardized health-related quality of life assessment (Child Health Questionnaire), extent of brain damage, and results of a comprehensive neurologic examination (Pediatric Stroke Outcome Measure) were investigated. Parent health was assessed using the Short-Form 36 General Health Survey. Activity limitation was evident in the domains of education, self-care, and motor skills. There was very good interobserver agreement using the new activity limitation scale between the occupational therapist and pediatric neurologist (Cohen's kappa = 0.88). In comparison with population norms, the subjects scored below average in both physical and psychologic health. There was a clear relationship between radiologically apparent extent of brain damage, degree of impairment, and functional outcome. Parental health also rated generally lower than expected. This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs.