Biomedical subjects
L Bernardi
Publications and source records attributed to L Bernardi.
Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure.
BACKGROUND: In chronic heart failure (CHF), impaired pulmonary function can independently contribute to oxygen desaturation and reduced physical activity. We investigated the effect of breathing rate on oxygen saturation and other respiratory indices. METHODS: Arterial oxygen saturation (SaO2) and respiratory indices were recorded during spontaneous breathing (baseline) and during controlled breathing at 15, six, and three breaths per min in 50 patients with CHF and in 11 healthy volunteers (controls). 15 patients with CHF were randomly allocated 1 month of respiratory training to decrease their respiratory rate to six breaths per min. Respiratory indices were recorded before training, at the end of training, and 1 month after training. FINDINGS: During spontaneous breathing, mean SaO2 was lower in CHF patients than in controls (91-4% [SD 0.4] vs 95.4% [0.2], p<0.001). Controlled breathing increased SaO2 at all breathing rates in patients with CHF. Compared with baseline, minute ventilation increased at 15 breaths per min (+45.9% [9.8], p<0.01), did not change at six breaths per min, and decreased at three breaths per min (-40.3% [4.8], p<0.001). In the nine CHF patients who had 1 month of respiratory training, resting SaO2 increased from 92.5% (0.3) at baseline to 93.2% (0.4) (p<0.05), their breathing rate per min decreased from 13.4 (1.5) to 7.6 (1.9) (p<0.001), peak oxygen consumption increased from 1157 (83) to 1368 (110) L/min (p<0.05), exercise time increased from 583 (29) to 615 (23) min/s (p<0.05), and perception of dyspnoea reduced from a score of 19.0 (0.4) to 17.3 (0.9) on the Borg scale (p<0.05). There were no changes in the respiratory indices in the patients who did not have respiratory training. INTERPRETATION: Slowing respiratory rate reduces dyspnoea and improves both resting pulmonary gas exchange and exercise performance in patients with CHF.
Influence of type of surgery on the occurrence of parasympathetic reinnervation after cardiac transplantation.
BACKGROUND: Cardiac autonomic reinnervation after human cardiac transplantation has been demonstrated frequently but to date only for sympathetic efferents. Standard surgical techniques leave many parasympathetic branches intact in the original atria and thus with less stimulus to reinnervate the donor atria. METHODS AND RESULTS: We used changes in the RR-interval power spectrum induced by sinusoidal modulation of arterial baroreceptors by neck suction at different frequencies to detect both parasympathetic and sympathetic reinnervation in 79 subjects with "standard" and 10 "bicaval" heart transplants. In 24 subjects (17 standard and 7 bicaval), the protocol was repeated 6 and 11 months after transplantation. Neck suction at 0.20 Hz produced a component at 0.20 Hz in the RR-interval spectrum not due to respiration (fixed at 0.25 Hz), which suggested parasympathetic reinnervation, in 4 of 10 bicaval but in only 2 of 79 standard transplant subjects (whose recipient atria underwent >50% resection to remove scars of previous interventions), P<.001. In only 1 (bicaval) transplant subject was parasympathetic reinnervation present 6 months after transplantation (confirmed 3 months later); in 4 subjects, it was absent at 6 months but appeared after 11 months after transplantation. Atropine (0.04 mg/kg i.v.) abolished the response to fast (0.20 Hz) and reduced that to slow stimulation, confirming the presence of parasympathetic reinnervation (4 subjects). CONCLUSIONS: Parasympathetic reinnervation depends on the surgical technique: because bicaval surgery cuts all sympathetic and parasympathetic nerves, regeneration might be stimulated similarly in both branches. Standard surgery cuts only approximately 50% of sympathetic fibers; most recipient parasympathetic axons remain intact, hence their regeneration might not be stimulated.
Cardiovascular autonomic testing in adolescents with type I (insulin-dependent) diabetes mellitus: an 18-month follow-up study.
1. Autonomic abnormalities are frequent in adult patients with diabetes mellitus and progress slowly; little is known about frequency and progression of autonomic abnormalities in childhood. 2. To assess whether autonomic abnormalities are already present in childhood, we evaluated the cardiovascular reflexes, the spectral analysis of spontaneous fluctuations in RR interval and blood pressure (low- and high-frequency), and the baroreflex sensitivity at rest, and after vagal (controlled breathing) and sympathetic activation (tilting) in 25 adolescents with Type I diabetes mellitus, aged 10-17 years, at baseline and after 18 months follow-up, and in 20 age- and sex-matched controls. 3. Cardiovascular reflexes were similar in both patients and controls. Similar significant changes in percentage low- and high-frequency (P < 0.005) from rest to tilting and to control breathing were observed in both patients and controls. The baroreflex sensitivity was also similar in patients and controls. Mild and non-systematic correlations were observed between autonomic tests and disease duration or metabolic control. After 18 months follow-up no changes were observed in any of the measured variables. Correlations with metabolic control remained unchanged. 4. These results indicate a substantial stability of cardiovascular autonomic function in childhood diabetes, and suggest that autonomic abnormalities are likely to develop at an older age.
Cardiovascular autonomic modulation and activity of carotid baroreceptors at altitude.
1. To assess the effects of acute exposure to high altitude on baroreceptor function in man we evaluated the effects of baroreceptor activation on R-R interval and blood pressure control at high altitude. We measured the low-frequency (LF) and high-frequency (HF) components in R-R, non-invasive blood pressure and skin blood flow, and the effect of baroreceptor modulation by 0. 1-Hz sinusoidal neck suction. Ten healthy sea-level natives and three high-altitude native, long-term sea-level residents were evaluated at sea level, upon arrival at 4970 m and 1 week later.2. Compared with sea level, acute high altitude decreased R-R and increased blood pressure in all subjects [sea-level natives: R-R from 1002+/-45 to 775+/-57 ms, systolic blood pressure from 130+/-3 to 150+/-8 mmHg; high-altitude natives: R-R from 809+/-116 to 749+/-47 ms, systolic blood pressure from 110+/-12 to 125+/-11 mmHg (P<0.05 for all)]. One week later systolic blood pressure was similar to values at sea level in all subjects, whereas R-R remained elevated in sea-level natives. The low-frequency power in R-R and systolic blood pressure increased in sea-level natives [R-R-LF from 47+/-8 to 65+/-10% (P<0.05), systolic blood pressure-LF from 1.7+/-0. 3 to 2.6+/-0.4 ln-mmHg2 (P<0.05)], but not in high-altitude natives (R-R-LF from 32+/-13 to 38+/-19%, systolic blood pressure-LF from 1. 9+/-0.5 to 1.7+/-0.8 ln-mmHg2). The R-R-HF decreased in sea-level natives but not in high-altitude natives, and no changes occurred in systolic blood pressure-HF. These changes remained evident 1 week later. Skin blood flow variability and its spectral components decreased markedly at high altitude in sea-level natives but showed no changes in high-altitude natives. Neck suction significantly increased the R-R- and systolic blood pressure-LF in all subjects at both sea level and high altitude.3. High altitude induces sympathetic activation in sea-level natives which is partially counteracted by active baroreflex. Despite long-term acclimatization at sea level, high-altitude natives also maintain active baroreflex at high altitude but with lower sympathetic activation, indicating a persisting high-altitude adaptation which may be genetic or due to baroreflex activity not completely lost by at least 1 year's sea-level residence.
Hypoxic ventilatory responses and gas exchange in patients with Parkinson's disease.
Ventilatory responses to isocapnic, progressive hypoxic rebreathing (HVR), in supine and sitting positions, lung ventilation and gas exchange while breathing air and during 5 min of breathing 11% O2 in N2 were studied in 12 healthy young (20-28 years), 5 old (57-73 years) male subjects, and in 7 male patients with Parkinson's disease (PD) aged 55-67 years. The piecewise linear approximation technique was used for evaluation of the ventilatory response curves, which allowed a separate analysis of slopes during minor and severe hypoxia. It has been shown that body position affected HVR. In the range of PETO2 from 60 to 35 mm Hg, the ventilatory response in the sitting position was higher than supine: in young persons by 43%, in healthy old persons by 76%, and in the PD patients by 211%. No significant differences in HVR to minor hypoxia (PETO2 from 100 to 60 mm Hg) were found in the 3 groups. During severe hypoxia (PETO2 from 60 to 35 mm Hg) the slope of minute ventilation versus O2 was 4.6 (supine) and 2.6 (sitting) times greater in healthy old men than PD patients' slopes. PD patients compared to old controls had 32% lower alveolar ventilation, 10% lower PETO2 and 15% elevation of PETCO2 while breathing air; similar differences were found while the patients were breathing 11% O2. The reduced alveolar ventilation under severe hypoxia in patients with PD could not be attributed to mechanical restriction of lung function. We suggest that the discrepancy in HVR under minor and severe hypoxia results from dysfunction in chemoreception associated with Parkinsonism.
[Mixed mesodermal tumor of the ovary. Description of a case with a small primary neoplastic mass. Anatomo-clinical and histogenetic considerations].
We describe a rare case of small mixed mesodermal tumor of the ovary (cm 1.5 in diameter) with widespread, clinically prevalent, peritoneal metastases. Some histological and immunohistochemical findings according with histogenetical conversion theory are discussed.
[Cardiovascular reflexes in subjects with heart transplant].
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Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors.
BACKGROUND: We investigated whether respiratory sinus arrhythmia (RSA) in healthy humans originated from central neuronal oscillations or from peripheral baroreceptors responding to respiratory changes in venous return. METHODS AND RESULTS: During subjects' controlled breathing we used sinusoidal neck suction to influence RSA (spectral analysis of RR interval). In 11 subjects, 20-second apnea greatly reduced RSA, which was restored by neck suction at the frequency of respiration. Counteracting the respiration-induced cycles of carotid blood pressure decreased RSA in 13 subjects (from 2136 +/- 682 to 1372 +/- 561 ms2, P < .01). The critical phase of this neck suction was constant for each subject at around the phase shift (with regard to respiration-related fluctuations of blood pressure) best for smoothing respiratory (mechanical) changes in blood pressure. Suction of a non-baroreceptor area (the thigh) did not affect RSA. In 4 subjects, to separate the effects of peripheral baroreceptor afferents from respiration-entrained central oscillation (15 breaths/min), we cycled the neck suction at 12 cycles/min. Increasing neck suction from -7 to -30 mm Hg increased the ratio of the power of the 12 cycles compared with the 15-cycle RSA oscillation in RR interval spectral analysis from 0.26 to 2.57. A 12-cycle/min suction of an area other than the neck had little effect on the RR interval spectrum. CONCLUSIONS: RSA can be mimicked or reduced by stimulation of arterial baroreceptors with cycles of appropriately phased neck suction at the frequency of respiration. This suggests an important influence of the arterial baroreceptors in the generation of RSA in conscious humans.
Reduction of 0.1 Hz microcirculatory fluctuations as evidence of sympathetic dysfunction in insulin-dependent diabetes.
OBJECTIVE: Loss of spontaneous fluctuations in resting microcirculatory flow has been described in diabetes mellitus, but its mechanism remains unexplained. METHODS: The autonomic control of forearm skin microcirculation was investigated in 23 insulin-dependent diabetic human subjects (median age 39 years, range 27-50) and in 23 age-matched controls (median age 38 years, range 20-57), by laser-Doppler flowmetry. Using spectral analysis of spontaneous microvascular fluctuations, we measured the power of 0.1 Hz ('10-second rhythm') fluctuations, dependent on sympathetic control, and of respiration-related, high-frequency fluctuations, due to the transmission of mechanical chest activity. Autonomic function abnormalities were assessed by 5 tests of cardiovascular reflexes. RESULTS: Abnormalities in cardiovascular autonomic tests were present in 7/23 patients: deep breathing was abnormal 4 in patients, standing in 2, handgrip in 3, cross-correlation in 4, and Valsalva ratio in 0. The power of 0.1 Hz microcirculatory fluctuations was significantly lower in diabetic than in control subjects (2.57 +/- 0.16 vs 3.48 +/- 0.09 In-mV2, mean +/- s.e.m., P < 0.001), whereas that of respiratory fluctuations was similar (2.60 +/- 0.24 vs 2.56 +/- 0.19 In-mV2, P = n.s.). The 0.1 Hz power was 2 standard deviations below the mean of controls (P < 0.05) in 13/23 diabetic patients; this abnormality was significantly more frequent than abnormalities in any other autonomic test (P < 0.001). CONCLUSIONS: Since the observed reduction was confined to those microvascular fluctuations under autonomic control, but not to those dependent on passive mechanical transmission, the reduction in spontaneous microcirculatory vasomotion appears to be determined mainly by sympathetic dysfunction. Sympathetic impairment of skin microvascular control seems to be a common finding, and is probably an early index of autonomic dysfunction in insulin-dependent diabetes.
Acute and persistent effects of a 46-kilometer wilderness trail run at altitude: cardiovascular autonomic modulation and baroreflexes.
OBJECTIVE: To test the hypothesis that prolonged physical exercise induces long-lasting effects on blood pressure and heart rate we studied 17 endurance runners before and after the 1995 Sandia Wilderness Crossing Research Run (46 km of rocky trails, average altitude 2500 m). METHODS: We evaluated the response of the cardiovascular system to sympathetic stimulation by orthostatism and to sympathetic and parasympathetic carotid baroreceptor stimulations by sinusoidal neck suction at different frequencies (sympathetic activity on blood pressure by low-frequency stimulation, parasympathetic activity on RR interval by high-frequency stimulation). We used power spectral analysis of beat-to-beat RR interval, systolic and diastolic non-invasive blood pressure, in order to quantify the respiratory fluctuations (depending on vagal activity on the RR interval) and the slower non-respiratory fluctuations, depending on sympathetic activity on the blood pressure. Recordings were performed 24 h before, and 30 min, 24 h and 48 h after the run. RESULTS: Thirty minutes after the race we found reduced blood pressure, signs of relative sympathetic predominance (increased RR interval low-frequency/high-frequency ratio from 0.65 +/- 0.15 to 1.63 +/- 0.37, P < 0.05), reduced effect of parasympathetic baroreceptor stimulation (decrease in RR interval high-frequency neck-suction synchronous oscillations, from 5.33 +/- 0.34 to 3.55 +/- 0.37 ln-ms2, P < 0.005), unchanged blood pressure responses to sympathetic stimulations; 24 h after the race, the response to parasympathetic stimulation was increased (to 6.44 +/- 0.32 ln-ms2, P < 0.0005) compared to baseline (24 h before the race), whereas sympathetic stimulation by neck suction had no longer an effect on blood pressure. CONCLUSION: The acute effects of prolonged exertion are associated with a relative increase in sympathetic activity. Twenty-four hours after this race an increased sensitivity to vagal and reduced sensitivity to sympathetic baroreflex stimulation was found. In this field study at altitude we found long-lasting effects on cardiovascular autonomic modulation after physical exertion.
Distinctive electrophysiological features of denervated muscle in uremic patients.
Abnormal spontaneous activity is a hallmark of acute or subacute denervation of skeletal muscle, particularly in patients with uremic neuropathy. We report 5 patients in whom such activity was unexpectedly minimal or absent.
Genetics of renal mechanisms of primary hypertension: the role of adducin.
PURPOSE: To summarize data concerning the identification of adducin as a 'candidate' gene in the Milan hypertensive strain of rats (MHS), a genetic model of essential hypertension, and in human essential hypertension. RESULTS: The sequence of events from renal function to cell membrane ion transports and finally to the molecular defect has been established in MHS rats. This led to the identification of polymorphisms in the cytoskeletal protein adducin. These polymorphisms are involved in blood pressure regulation in these rats. A linkage and an association study on Caucasian populations support the involvement of adducin in human hypertension also. A polymorphism of alpha-adducin gene is significantly associated with human hypertension. In particular, both in humans and in rats, adducin polymorphisms affect kidney function by modulating the overall capacity of tubular epithelial cells to transport ions. CONCLUSIONS: Adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied.
Lack of peripheral modulation of cardiovascular central oscillatory autonomic activity during apnea in humans.
Respiratory sinus arrhythmia (RSA) high-frequency oscillations (HF) and slow fluctuations in heart rate (LF) are thought to result from entrainment of a medullary oscillator, from the baroreflex, or from a combination of both central and baroreflex mechanisms. We sought to distinguish between the alternatives by examining with spectral analysis the behavior of heart rate (R-R interval) and blood pressure in 10 healthy subjects (mean age 27 +/- 1 yr) during apnea, altering the rate of preapnea entrainment stimuli by changing the frequency either of respiration (controlled at 0.1 or 0.25 Hz) or of baroreceptor stimulation by sinusoidal neck suction (0 to -30 mmHg, 0.1 or 0.2 Hz). During apnea the RSA-EF power decreased (from 6.73 +/- 0.15 to 3.67 +/- 0.10 In ms2: P < 0.0001), regardless of preapnea conditions, whereas LF power was reduced only if preceded by 0.1-Hz respiration or neck suction [from 8.71 +/- 0.18 to 6.52 +/- 0.11 In ms2 (P < 0.001) and from 8.31 +/- 0.23 to 6.90 +/- 0.38 In ms2 (P < 0.01), respectively]. The LF frequency seen in the R-R interval during apnea was slower than the spontaneous LF during 0.25-Hz breathing (0.082 +/- 0.01 vs. 0.112 +/- 0.001 Hz, P < 0.001), but the maneuvers during preapnea had no influence on the observed frequency or other characteristics of the slow oscillations during apnea. Moreover, we found no evidence of a progressive decrease in the power of the oscillation during apnea. The same behavior was observed on the mean blood pressure signal. In conclusion, a slow rhythm is present during apnea. In healthy subjects at rest the characteristics of this oscillation indicate that it could be generated by a central oscillator this may thus contribute to the origin of LF present during normal respiration, in addition to the baroreflex.
Synchronous and baroceptor-sensitive oscillations in skin microcirculation: evidence for central autonomic control.
To determine whether skin blood flow is local or takes part in general regulatory mechanisms, we recorded laser-Doppler flowmetry (LDF; left and right index fingers), blood pressure, muscle sympathetic nerve activity (MSNA), R-R interval, and respiration in 10 healthy volunteers and 3 subjects after sympathectomy. We evaluated 1) the synchronism of LDF fluctuations in two index fingers, 2) the relationship with autonomically mediated fluctuations in other signals, and 3) the LDF ability to respond to arterial baroreflex stimulation (by neck suction at frequencies from 0.02 to 0.20 Hz), using spectral analysis (autoregressive uni- and bivariate, time-variant algorithms). Synchronous LDF fluctuations were observed in the index fingers of healthy subjects but not in sympathectomized patients. LDF fluctuations were coherent with those obtained for blood pressure, MSNA, and R-R interval. LDF fluctuations were leading blood pressure in the low-frequency (LF; 0.1 Hz) band and lagging in the respiratory, high-frequency (HF; approximately 0.25 Hz) band, suggesting passive "downstream" transmission only for HF and "upstream" transmission for LF from the microvessels. LDF fluctuations were responsive to sinusoidal neck suction up to 0.1 Hz, indicating response to sympathetic modulation. Skin blood flow thus reflects modifications determined by autonomic activity, detectable by frequency analysis of spontaneous fluctuations.
[Diagnostic accuracy of teleradiology in thoracic and abdominal diseases].
For one year now, teleradiology has linked the "S. Marcello" Hospital to the Department of Radiology of "Del Ceppo." Hospital in Pistoia, 30 kilometers away. Plain films are digitized (Lumiscan 50, Philips), transmitted over a dedicated standard telephone line and displayed at 1024 x 1024 x 8 bits. To study the diagnostic accuracy of teleradiology in chest and abdominal conditions, we digitized and transmitted to the Pistoia Dept. of Radiology, a sample of 156 (96 chest and 60 abdominal) emergency examinations made in "S. Marcello" Hospital from January through November, 1995. The patients were 81 women (mean age: 69 years) and 75 men (mean age: 66 years); the age range was 17-93 years. Three radiologists independently reviewed the images in the Pistoia Dept. of Radiology on a digital workstation enabled to manipulate images. They filled in some given forms specific for chest and abdominal radiography, which were compared with the same forms filled in by the radiologist in "S. Marcello" Hospital who reviewed plain films. The differences were never clinically important; they concerned emphysema (4 false positives and 2 false negatives), congestion of the hila (2 false positives and 2 false negatives) and abnormal air in small bowel and colon (2 false positives and 2 false negatives). We believe these differences to be related to interobserver variability. The diagnostic accuracy of monitor image interpretation by the three radiologists who reviewed digitized radiographs exceeded 96% for both chest and abdominal examinations, which figure compares with literature data on high resolution workstations.
gamma-Linolenic acid supplementation can affect cancer cell proliferation via modification of fatty acid composition.
We examined the effect of gamma-linolenic acid (GLA) supplementation on the growth and fatty acid composition of three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), in order to evaluate the relationship between GLA-induced tumor cell death and the distribution of fatty acids in tumor cells. At the highest GLA concentrations (10 and 20 micrograms/ml), the DNA synthesis was completely abolished; at 5 micrograms/ml GLA only SW-620 cells did not proliferate, while CHP-212 and TG cells showed a residual [3H]-thymidine incorporation. GLA levels were very low in cells grown in control medium; GLA supplementation caused a significant incorporation of GLA itself in all the cell lines at each concentration. In TG and CHP-212 cells, GLA was metabolized, although to a different extent, to dihomo-gamma linolenic acid and arachidonic acid. SW-620 cells neither elongated nor desaturated the incorporated GLA. The highest cytostatic effect was reached when GLA was not transformed into its metabolites, suggesting that the GLA toxicity to tumor cells is not dependent on metabolites but is due to GLA itself.
Physical activity influences heart rate variability and very-low-frequency components in Holter electrocardiograms.
OBJECTIVE: A major proportion of RR interval variability in long-term recordings is due to slow (< 0.03 Hz) fluctuations, which seem to be a good predictor of survival after myocardial infarction, whose origin remains unclear. METHODS: To study the effect of physical activity we compared by spectral analysis of the RR interval in 10 healthy human subjects (aged 28[s.e. 2] years) during 1-h periods each of rest (no activity), alternating rest and mild exercise (rhythmic activity), and normal spontaneous (random) activity. RESULTS: Compared to rest, during both random and rhythmic activities, the RR variance increased significantly (from 5802[1030] to 13388[1448] ms2, P < 0.05, and to 24959[2901], P < 0.001) due to an increase in power below 0.03 Hz (from 3017[467] to 9606[966] ms2, P < 0.01, and to 21 103[2298] ms2, P < 0.001) which explained 55.4, 73.2 and 86.1% of total RR variance, respectively. CONCLUSIONS: The amount of RR variability and its slower fluctuations largely depend on physical activity, regardless of its regular or irregular occurrence. Attempts to predict cardiovascular prognosis on the basis of RR fluctuations should therefore take account of the confounding effect of physical activity since healthier subjects would probably be more active.