Evidence in the human of a hypotensive and a bradycardic effect after mouth opening maintained for 10 min.

PURPOSE: We have recently shown that in humans submaximal mouth opening associated with partial masticatory movements for 10 min is followed by a small but significant and prolonged reduction of blood pressure and heart rate. We here report the effects of a fixed mouth opener. METHODS: In 22 seated normotensive volunteers the effect on blood pressure and heart rate was studied in randomized order after fixed mandibular extension and after a control procedure consisting in keeping a stick between the incisor teeth (both for 10 min). Automated recordings every 10 min were done for 40 min before and 120 min following the procedure. RESULTS: Two-way ANOVA for repeated measures on absolute values (actual recordings) and on changes from baseline revealed that, compared to controls, systolic, diastolic and mean blood pressure and heart rate were significantly lower after mandibular extension. Compared to controls, mandibular extension induced an average blood pressure drop of 2.88 mmHg (systolic), 2.55 mmHg (diastolic) and 2.42 mmHg (mean) over the entire observation period. The average decline over the central part of the observation period (30th to 80th min) was, respectively, of 3.62, 3.70 and 3.61 mmHg. The decrements of heart rate were of 2.11 and 2.66 beats per min. All these differences were statistically significant. The hypotensive and bradycardic responses persisted for 70-120 min. CONCLUSIONS: This study shows that, in normotensives, a single fixed submaximal mouth opening for 10 min is followed by prolonged albeit small reductions of blood pressure and heart rate.

Differential magnetic field effects on heart rate and nociception in anosmic pigeons.

Several studies have shown that exposure to altered magnetic fields affects nociception by suppressing stress-induced hypoalgesia, and that this effect is reduced or abolished if the treatment is performed in the absence of light. This raises the question as to whether other sources of sensory stimuli may also modulate these magnetic effects. We investigated the possible role of olfaction in the magnetically induced effects on sensitivity to nociceptive stimuli and heart rate (HR) in restraint-stressed homing pigeons exposed to an Earth-strength, irregularly varying (<1 Hz) magnetic field. The magnetic treatment decreased the nociceptive threshold in normally smelling birds and an opposite effect was observed in birds made anosmic by nostril plugging. Conversely, no differential effect of olfactory deprivation was observed on HR, which was reduced by the magnetic treatment both in smelling and anosmic pigeons. The findings highlight an important role of olfactory environmental information in the mediation of magnetic effects on nociception, although the data cannot be interpreted unambiguously because of the lack of an additional control group of olfactory-deprived, non-magnetically exposed pigeons. The differential effects on a pigeon's sensitivity to nociceptive stimulus and HR additionally indicate that the magnetic stimuli affect nociception and the cardiovascular system in different ways.

Prolonged hypotensive and bradycardic effects of passive mandibular extension: evidence in normal volunteers.

Various procedures involving stimulations of facial regions are known to induce so-called trigemino-cardiac reflexes that entail a decrease of heart rate and blood pressure. We here report the effects of a specific stimulation that consists in a submaximal passive mandibular extension obtained by means of a dilatator applied for 10 minutes between the upper and lower incisor teeth, associated with partial active masticatory movements. Blood pressure and heart rate were determined in 18 young normal volunteers by Omron M4, before (20 minutes), during (10 minutes) and after mandibular extension (80 minutes) and under control conditions (same overall duration without stimulation). While control values remained stable, mandibular extension was followed by a progressive decline of both blood pressure (up to about 12/11 mmHg) and heart rate (up to about 13 bpm), statistically confirmed by ANOVA both on absolute values and on changes from basal values. The decline of systolic blood pressure and heart rate significantly correlated with basal values. The present findings indicate that submaximal opening of the mouth, associated to partial masticatory movements, induces a prolonged reduction of blood pressure and heart rate in normotensive volunteers.

Single-shot cardiorenal scintigraphy with 99mTc-tetrofosmin: a dynamic characterization at rest and during adenosine infusion.

UNLABELLED: Renal function is known to be a strong predictor of cardiovascular prognosis, and cardiorenal disease is increasingly investigated in medical research. In this study, we tested the hypothesis that a single combined cardiorenal scintigraphy examination with the perfusion tracer (99m)Tc-tetrofosmin is feasible and may allow the simultaneous investigation of cardiac and renal pathology in cardiovascular patients. METHODS: Thirty patients scheduled for dual-day gated SPECT also gave their informed consent for a renal acquisition after a single injection of 370 MBq of (99m)Tc-tetrofosmin, at rest (30 patients) or with adenosine (21 patients), and to undergo an additional standard renal study with the glomerular tracer (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) (74 MBq) after 1 wk (24 patients). Kidney images and renograms were obtained. Renal uptake index, expressed as the percentage ratio of kidney counts cumulated over the second minute after injection to the administered dose, was calculated as a functional renal parameter. Time to peak activity and separate kidney percentage uptake (as the percentage contribution of each kidney to total renal uptake) were also calculated. RESULTS: Compared with (99m)Tc-DTPA, (99m)Tc-tetrofosmin provided better-quality kidney images, with a higher uptake index (13.17% +/- 4.76% vs. 8.33% +/- 2.45%, P < 0.001) and with comparable separate kidney percentage uptake and times to peak activity. (99m)Tc-tetrofosmin uptake index was significantly lower in the patients who were more compromised according to renal and cardiovascular functional parameters, and correlated with (99m)Tc-DTPA uptake index (r = 0.77, P < 0.001), serum creatinine (r = 0.59, P < 0.005), log brain natriuretic peptide N-terminal levels (r = -0.65, P < 0.005), myocardial and carotid intima-media wall thickness (for both, r = -0.61, P < 0.005), and the Doppler index of renal vascular resistance (r = -0.60, P < 0.005). In the 21 patients who underwent the provocative test, adenosine induced a significant decrease in renal (99m)Tc-tetrofosmin uptake index (from 14.12% +/- 4.50% to 11.81% +/- 3.33%, P < 0.005) suggesting a decrement in renal perfusion or function. CONCLUSION: (99m)Tc-tetrofosmin cardiorenal scintigraphy is feasible at low cost as a single-shot study and may allow both the evaluation of renal morphology and renograms during a cardiac study and the calculation of renal functional parameters.

Investigations of a simulated geomagnetic field experienced by the International Space Station on attentional performance.

We have previously reported that the exposure to an abnormal magnetic field simulating the one encountered by the International Space Station (ISS) orbiting around the Earth may enhance autonomic response to emotional stimuli. Here we report the results of the second part of that study which tested whether this field also affects cognitive functions. Twenty-four volunteers participated in the study, 12 exposed to the natural geomagnetic field and 12 to the magnetic field encountered by ISS. The test protocol consisted of a set of eight tests chosen from a computerized test battery for the assessment of attentional performance. The duration of exposure was 90 min. No effect of exposure to ISS magnetic field was observed on attentional performance.

Evidence in hypertensive rats of hypotensive effect after mandibular extension.

Previous studies in anesthetized normotensive rats demonstrated that a single mouth opening for 10 min obtained by an ad hoc dilator (mandibular extension [ME]) produced a blood pressure reduction by about 20 mmHg lasting for about 2 h and that once-repeated ME prolonged this effect. We here describe these effects in hypertensive rats. Mean (intra) arterial blood pressure (MABP) and heart rate (HR) was followed for up to a maximum of 470 min after single or repeated 10 min-lasting ME in two groups of anesthetized, male, 6-9 months old hypertensive rats. In one group, hypertension was induced by dexamethasone (20 µg/kg/day, subcutaneously for 7 days; Dex-HT); the other group was spontaneously hypertensive rats (SHR). Studies were done, in Dex-HT rats, after only surgical procedures (no ME, sham-operated rats), single ME, early repeated (after 10 min) ME (ER-ME) and late repeated (after 160 min) ME (LR-ME) and, in SHR, after only surgical procedures and ER-ME. One-way ANOVA for repeated measures revealed no significant effect on MABP and HR in sham-operated groups. In Dex-HT rats, single ME was followed by a significant MABP decline by 25 mmHg, lasting for 100 min; ER-ME and LR-ME were followed by an even greater significant MABP decline by 40 mmHg, which outlasted the experimental observation period. In SHR, ER-ME gave similar results as in Dex-HT rats. HR significantly declined in all, except sham-operated groups. In conclusions, ME is followed by a prolonged MABP decline also in hypertensive rats. This effect is even more pronounced, in length and magnitude, after repeated ME.

Pain perception and electromagnetic fields.

A substantial body of evidence has accumulated showing that exposure to electromagnetic fields (EMFs) affects pain sensitivity (nociception) and pain inhibition (analgesia). Consistent inhibitory effects of acute exposures to various EMFs on analgesia have been demonstrated in most studies. This renders examinations of changes in the expression of analgesia and nociception a particularly valuable means of addressing the biological effects of and mechanisms underlying the actions of EMFs. Here we provide an overview of the effects of various EMFs on nociceptive sensitivity and analgesia, with particular emphasis on opioid-mediated responses. We also describe the analgesic effects of particular specific EMFs, the effects of repeated exposures to EMFs and magnetic shielding, along with the dependence of EMF effects on lighting conditions. We further consider some of the underlying cellular and biophysical mechanisms along with the clinical implications of these effects of various EMFs.

Repeated Mandibular Extension in Rat: A Procedure to Modulate the Cerebral Arteriolar Tone.

Previous data have shown both in the rat and in the human that a single mandibular extension lasting 10 min induces a significant important and prolonged reduction in blood pressure and heart rate, affecting also rat pial microcirculation by the release of endothelial factors. In the present work, we assessed whether repeated mandibular extension could further prolong these effects. We performed two mandibular extensions, the second mandibular extension being applied 10 min after the first one. The second mandibular extension produced a reduction in blood pressure and heart rate for at least 240 min. As in the case of a single mandibular extension, pial arterioles dilated persisting up to 140 min after the second extension. Spectral analysis on 30 min recordings under baseline conditions and after repetitive mandibular extensions showed that the pial arterioles dilation was associated with rhythmic diameter changes sustained by an increase in the frequency components related to endothelial, neurogenic, and myogenic activity while a single mandibular extension caused, conversely, an increase only in the endothelial activity. In conclusion, repetitive mandibular extension prolonged the effects of a single mandibular extension on blood pressure, heart rate and vasodilation and induced a modulation of different frequency components responsible of the pial arteriolar tone, in particular increasing the endothelial activity.

Simulation of the geomagnetic field experienced by the International Space Station in its revolution around the Earth: effects on psychophysiological responses to affective picture viewing.

There is evidence suggesting that exposure to an abnormal magnetic environment may produce psychophysiological effects related to abnormalities in responses to stress. This may be of relevance for space medicine where astronauts are exposed to a magnetic field different from that exerted by the Earth. Aim of this study was to assess how the exposure of the head to a magnetic field simulating the one encountered by the International Space Station (ISS) during a single orbit (90 min) around the Earth affects the cardiovascular and psychophysiological parameters. Twenty-four human volunteers were studied double blindly in random order under sham and magnetic exposure. During exposure, the persons were shown a set of pictures of different emotional content while subjective self-rating, skin conductance (SC), blood pressure (BP), and heart rate (HR) were measured. In addition, BP, HR, and tooth pain threshold were assessed before and after exposure. While subjects were under magnetic exposure, skin conductance was strongly differentiated (F(2,36)=22.927; p=0.0001), being high during emotionally involving (positive and negative) pictures and low during neutral pictures. Conversely, when subjects were under sham exposure, no significant differences were observed. There was, however, a trend for higher heart rate during picture viewing under magnetic exposure as compared to sham exposure. No effects were found for the other variables. These results suggest that an abnormal magnetic field that simulates the one encountered by ISS orbiting around the Earth may enhance autonomic response to emotional stimuli.

Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment: a double-blind, randomized study.

OBJECTIVE: To compare zofenopril + hydrochlorothiazide (Z + H) vs. irbesartan + hydrochlorothiazide (I + H) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy. METHODS: After a 1-week run-in, 230 ISH patients (office SBP ≥ 140  mmHg and DBP < 90  mmHg + daytime SBP ≥ 135  mmHg and daytime DBP < 85  mmHg) were randomized double-blind to 18-week treatment with Z + H (30 + 12.5  mg) or I + H (150 + 12.5  mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20  mg added at 12 weeks in nonnormalized patients. RESULTS: In the full analysis set (n = 216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P = 0.888) with Z + H [7.7 (10.7, 4.6)  mmHg, n = 107] and I + H [7.9 (10.7, 5.0)  mmHg, n = 109]. Daytime SBP reductions were sustained during the study, and larger (P = 0.028) with low-dose Z + H at study end [16.2 (20.0, 12.5)  mmHg vs. 11.2 (14.4, 7.9)  mmHg I + H]. Daytime SBP normalization (<135 mmHg) rate was similar under Z + H and I + H at 6 and 12 weeks, but more common under Z + H at 18 weeks (68.2 vs. 56.0%, P = 0.031). Both drugs equally reduced SBP in the last 6 h of the dosing interval and homogeneously reduced SBP throughout the 24 h. The proportion of patients reporting drug-related adverse events was low (Z + H: 4.4% vs. I + H: 6.0%; P = 0.574). CONCLUSION: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H.

Effects of 50 Hz electromagnetic fields on electroencephalographic alpha activity, dental pain threshold and cardiovascular parameters in humans.

Recent studies indicate that exposure to extremely low frequency magnetic fields (ELF MFs) influences human electroencephalographic (EEG) alpha activity and pain perception. In the present study we analyse the effect on electrical EEG activity in the alpha band (8-13 Hz) and on nociception in 40 healthy male volunteers after 90-min exposure of the head to 50 Hz ELF MFs at a flux density of 40 or 80 microT in a double-blind randomized sham-controlled study. Since cardiovascular regulation is functionally related to pain modulation, we also measured blood pressure (BP) and heart rate (HR) during treatment. Alpha activity after 80 microT magnetic treatment almost doubled compared to sham treatment. Pain threshold after 40 microT magnetic treatment was significantly lower than after sham treatment. No effects were found for BP and HR. We suggest that these results may be explained by a modulation of sensory gating processes through the opioidergic system, that in turn is influenced by magnetic exposure.

Strengths and limitations of current pediatric blood pressure nomograms: a global overview with a special emphasis on regional differences in neonates and infants.

The availability of robust nomograms is essential for the correct evaluation of blood pressure (BP) values in children. A literature search was conducted by accessing the National Library of Medicine by using the keywords BP, pediatric and reference values/nomograms. A total of 43 studies that evaluated pediatric BP nomograms were included in this review. Despite the accuracy of the latest studies, many numerical and methodological limitations still remain. The numerical limitations include the paucity of data for neonates/infants and for some geographic areas (Africa/South America/East Europe/Asia) and ethnicities. Furthermore, the data on ambulatory BP and response to exercise are extremely limited, and the criteria for stress-test interruption are lacking. There was heterogeneity in the methodologies employed to perform the measurements, in the inclusion/exclusion criteria (often not reported), in the data normalization and the data expression (Z-scores/percentiles/mean values). Although most studies adjusted the measurements for age and/or height, the classification by specific age/height subgroups varied. Gender differences were generally considered, whereas other confounders (that is, ethnicity/geographic area/environment) were seldom evaluated. As a result, nomograms were heterogeneous, and when comparable, at times showed widely different confidence intervals. These differences are most likely because of both methodological limitations and differences among the populations studied. Some robust nomograms exist (particularly those from the USA); however, it has been demonstrated that if adopted in other countries/continents, they may generate an unpredictable bias in the evaluation of BP values in children. Actual pediatric BP nomograms present consistent limitations that affect the evaluation of BP in children. Comprehensive nomograms, which are based on a large population of healthy children (including neonates/infants) and use standardized methodology, are warranted for every country/region.

Pain threshold is reduced in depression.

Pain and depression may share common neurochemical substrates, therefore the study of pain sensation in depression might be valuable in the investigation of the pathophysiology of depression itself. In order to investigate the sensation of pain in depression, we measured pain threshold and sensory threshold by means of a dental tester, comparing a group of depressed patients with healthy volunteers. The results showed the presence of a higher sensory threshold and pain threshold in patients than in controls. This may be related to a hyperfunction of the opiate system, which in turn might be primary or secondary to a decreased modulatory function of other neurotransmitters, in particular of serotonin, whose abnormalities in depressive states are well-documented.

Effects of magnetic field exposure on open field behaviour and nociceptive responses in mice.

Results of previous studies have shown that nociceptive sensitivity in male C57 mice is enhanced by exposure to a regular 37 Hz or an irregularly varying (<1 Hz) electromagnetic field. In order to test whether these fields affect more generally mouse behaviour, we placed Swiss CD-1 mice in a novel environment (open field test) and exposed them for 2 h to these two different magnetic field conditions. Hence, we analysed how duration and time course of various behavioural patterns (i.e. exploration, rear, edge chew, self-groom, sit, walk and sleep) and nociceptive sensitivity had been affected by such exposure. Nociceptive sensitivity was significantly greater in magnetically treated mice than in controls. The overall time spent in exploratory activities was significantly shorter in both magnetically treated groups (< 1 Hz, 33% and 37 Hz, 29% of total time), than in controls (42%). Conversely, the time spent in sleeping was markedly longer in the treated groups (both 27% of total time) than in controls (11%). These results suggest that exposure to altered magnetic fields induce a more rapid habituation to a novel environment.

Trigeminocardiac reflex by mandibular extension on rat pial microcirculation: role of nitric oxide.

In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of Nω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times.

Right ventricular remodelling in systemic hypertension: a cardiac MRI study.

BACKGROUND: Consistent evidence shows an impact of systemic haemodynamic overload on the right ventricle, but its functional and structural consequences have received scarce attention for several reasons including the difficult application of conventional imaging techniques due to the complex shape and orientation of that cardiac chamber. AIMS: To evaluate whether mild to moderate, uncomplicated hypertension associates with abnormal right ventricular structure and function and how those changes relate to homologous changes in the left ventricle. Data were acquired by steady-state free-precession cardiac MRI, the state of the art tool for the morphological and functional evaluation of the right ventricle. MATERIALS AND METHODS: Twenty-five (12 women) uncomplicated, untreated, essential hypertensive patients were compared with 24 (13 women) sedentary normotensive controls of comparable age. Wall thickness, indexed ventricular mass, end-diastolic volumes, early peak filling rate, a correlate of diastolic relaxation, and ejection fraction were measured at both ventricles. Remodelling index, the ratio of ventricular mass to end-diastolic volume, was used as an index of concentricity. RESULTS: Right ventricular mass index, ventricular wall thickness and remodelling index were greater in hypertensive subjects and associated with reduced peak filling rate, a pattern consistent with concentric right ventricular remodelling. In the hypertensive group, positive, highly significant biventricular correlations existed between indexed mass, early peak filling rate and ejection fraction. CONCLUSIONS: Systemic hypertension associates with concentric right ventricular remodelling and impaired diastolic function, confirming that the unstressed ventricle is not immune to the effects of systemic hypertension. Structural and functional right ventricular adaptation to systemic hypertension tends to parallel the homologous modifications induced by systemic haemodynamic overload on the left ventricle.

Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension.

OBJECTIVES: Patients and animal models of arterial hypertension are characterized by structural and functional abnormalities of the coronary microcirculation. Using a translational approach, we ascertained whether antihypertensive treatment can reverse microvascular remodelling and improve myocardial perfusion. METHODS: In 20 hypertensive patients with left ventricular hypertrophy, blood pressure, left ventricular mass index and myocardial blood flow were measured at baseline and after 6 months of treatment with perindopril + indapamide. In spontaneously hypertensive rats, blood pressure, coronary flow and histomorphometry of intramural coronary arterioles were measured after 8 weeks of treatment with placebo or perindopril + indapamide. RESULTS: In patients, treatment decreased blood pressure (161 ± 10/96 ± 5 to 136 ± 12/81 ± 6 mmHg; P < 0.0001) and left ventricular mass index (93 ± 16 to 85 ± 17 g/m; P < 0.01) while increasing baseline (0.69 ± 0.13 to 0.88 ± 0.36 ml/min per g; P < 0.05) and hyperaemic myocardial blood flow (1.42 ± 0.32 to 1.94 ± 0.99 ml/min per g; P < 0.05). In rats treated with perindopril + indapamide (n = 11), blood pressure was 93 ± 18/55 ± 18 mmHg compared to 215 ± 18/161 ± 17 mmHg in placebo (n = 6; P < 0.001), baseline flow was unchanged whilst hyperaemic coronary flow was 19.89 ± 3.50 vs. 12.15 ± 0.99 ml/min per g, respectively (P < 0.01). The medial area of intramural arterioles was 1613 ± 409 with perindopril + indapamide and 8118 ± 901 µm with placebo (P < 0.001). CONCLUSION: In patients with arterial hypertension and left ventricular hypertrophy, perindopril + indapamide reduced blood pressure and left ventricular mass index and improved resting and hyperaemic myocardial blood flow. Data in rats provide evidence that the improvement in coronary flow observed after treatment is due to reverse remodelling of intramural coronary arterioles and improved microvascular function.

Early hypertension is associated with reduced regional cardiac function, insulin resistance, epicardial, and visceral fat.

Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47+/-1 years; body mass index: 28.4+/-0.6 kg m(-2); mean+/-SEM) included 13 with normal blood pressure (BP: 113+/-5/67+/-2 mm Hg), 13 with prehypertension (BP: 130+/-1/76+/-2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150+/-2/94+/-2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from -17.0+/-0.5% in normal blood pressure to -15.2+/-0.7% in prehypertension to -13.6+/-0.8% in those newly diagnosed with essential hypertension; P=0.004). Reduced circumferential strain was significantly associated with raised BP independent of age (r=0.41; P=0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function.