PubMed Health⌕ Search

Biomedical subjects

F Lombardi

Publications and source records attributed to F Lombardi.

At least 19 recordsLinked to original sources
PubMed1996

Linear and nonlinear dynamics of heart rate variability after acute myocardial infarction with normal and reduced left ventricular ejection fraction.

We analyzed heart rate variability (HRV) in 2 groups of patients after acute myocardial infarction with normal and reduced ejection fraction (EF) by considering both the power of the 2 major harmonic components at low and high frequency and 2 indexes of nonlinear dynamics, namely the 1/f slope and the correlation dimension D2. HRV of patients with a reduced EF was characterized by a diminished RR variance as well as a different distribution of the residual power in all frequency ranges, with lower values of the low-frequency component expressed in both absolute and normalized units, and of the low- to high-frequency ratio. In these patients we also observed a steeper slope of the negative regression line between power and frequency in the very low frequency range. The presence of a smaller fractal dimension was suggested by a lower D2. Thus, in patients after acute myocardial infarction with a reduced EF, the reduction in HRV is associated with a different distribution of the residual power in the entire frequency range, which suggests a diminished responsiveness of sinus node to neural modulatory inputs.

Case-Control Studies↗
PubMed1996

Heart rate variability in the early hours of an acute myocardial infarction.

The occurrence of an autonomic disturbance early in acute myocardial infarction (AMI) has been reported: signs of sympathetic activation were mainly observed in relation to an anterior localization, whereas signs of vagal overactivity were more frequent in inferior wall AMI. Information is limited in relation to the persistence of these alterations during the early hours of AMI. We studied 33 patients with an AMI within 188 +/- 16 minutes from the onset of symptoms and 1 week after hospital admission. From a 20-minute Holter recording, we computed with autoregressive methodology, time and frequency domain indexes of heart rate variability. At admission, patients with an anterior wall AMI exhibited a smaller RR variance (593 +/- 121 ms2) than did those with an inferior wall AMI (1,122 +/- 191 ms2). In both groups the spectral profile was characterized by a predominant (73 +/- 4 and 61 +/- 4 normalized units) low frequency and by a small (13 +/- 2 and 22 +/- 3 normalized units) high-frequency component, indicating the presence of a sympathetic excitation and of a diminished vagal modulation. Although signs of sympathetic activation were more evident in patients with anterior wall AMI, no evidence of a vagal hyperactivity was observed in patients with inferior wall AMI. In the latter group, we noticed 1 week after the acute event an increase in the low-frequency component, which reached the values observed in patients with anterior wall AMI. Thrombolysis did not affect heart rate variability parameters. Thus, this study suggests the presence of an autonomic disturbance characterized by signs of sympathetic excitation and of a reduced vagal modulation, which was more evident in patients with an anterior localization early after AMI.

Electrocardiography, Ambulatory↗
PubMed1996

Presence of vasomotor and respiratory rhythms in the discharge of single medullary neurons involved in the regulation of cardiovascular system.

We analyzed the discharges of 77 single neurons located in the rostral ventrolateral medulla (RVLM, n = 25), caudal ventrolateral medulla (CVLM, n = 18), lateral tegmental field (LTF, n = 19) and caudal raphe nuclei (n = 15). These recordings were made from 36 vagotomized and sinoaortic denervated cats that were either decerebrate (n = 27) or anesthetized with urethane (n = 9) and from 3 decerebrate cats with intact sinoartic and vagal nerves. These neurons were classified as sympathetic-related (n = 61) if spike triggered averaging showed that their naturally occurring discharges were correlated to either the cardiac related (2-6 Hz) or a faster (10 Hz) oscillation in inferior cardiac sympathetic nerve discharge. Neurons were classified as sympathetic-unrelated (n = 16) if they lacked these characteristics. We used autoregressive spectral techniques to detect additional slower oscillations hidden in the variability of neuronal discharge and possibly correlated to the oscillations of systolic arterial pressure (SAP). This analysis revealed the existence of a low frequency (LF) oscillation (0.12 +/- 0.02 Hz) in the discharges of 36 sympathetic-related and 9 sympathetic-unrelated neurons. In relation to 35 neurons in 21 animals there was also an LF component in SAP variability. In 29 instances the LF neuronal discharges and SAP variabilities were significantly correlated. In addition, there was a high frequency (HF) oscillation (0.34 +/- 0.06 Hz) in the discharges of 59 medullary neurons. In 56 cases the HF in neuronal discharge variability cohered to that in SAP variability. These data are the first to demonstrate the existence of an LF component in the discharges of individual medullary neurons, at least some of which were likely to be involved in the regulation of the cardiovascular system. Since these oscillations were evident in cats with section of sinoaortic and vagal nerves, they likely reflect central rhythmogenic properties.

Animals↗
PubMed1996

Classification of coupling patterns among spontaneous rhythms and ventilation in the sympathetic discharge of decerebrate cats.

The spontaneous low- and high-frequency rhythms in the sympathetic discharge of decerebrate artificially ventilated cats are affected by external ventilation. Two graphical methods (i.e. the space-time separation plot and the frequency tracking locus) are used to classify the non-linear interactions. The observed behaviours in the sympathetic discharge consist of phase-locked periodic dynamics (at various frequency ratios with ventilation), quasiperiodic and aperiodic patterns. They depend on the experimental condition. In control condition the sympathetic discharge appears more frequently locked to each ventilatory cycle (1:1 dynamics). However, some cases of quasiperiodic dynamics are found. A sympathetic activation stimulus, such as inferior vena cava occlusion, is able to synchronize slow rhythms in the sympathetic discharge to a subharmonic of ventilation. During a sympathetic inhibition stimulus, such as aortic constriction, 1:1 dynamics is detected but the amplitude of the sympathetic responses can be modulated by unlocked slow rhythms. Moreover some cases of aperiodic dynamics are observed. Vagotomy reduces the 1:1 coupling between sympathetic outflow and ventilation. Vagotomy plus spinalisation disrupts periodic dynamics in the sympathetic discharge so that irregular and complex patterns are found.

Animals↗
PubMed1996

Spectral analysis of short term R-Tapex interval variability during sinus rhythm and fixed atrial rate.

Analysis of heart rate variability has been proven useful in stratifying post myocardial patients at risk and in evaluating autonomic dysfunction. Recently augmented inter-lead variability of the QT interval has been associated with increased mortality as a result of arrhythmia and proposed as a marker of dispersion of ventricular repolarization. As the duration of the QT interval is largely dependent upon the length of the preceding cardiac cycle it is tempting to analyse whether neural mechanisms might also directly exert additional modulation. Using autoregressive algorithms we therefore analysed RR and R-Tapex interval variabilities in 15 normal subjects during sinus rhythm and in six patients with a fixed atrial rate. In controls mean R-Tapex interval and variance measured on the vector magnitude were, respectively, 245 +/- 6 ms and 5.1 +/- 0.7 ms2. Spectral analysis of R-Tapex indicated the presence of two spectral components which corresponded to the low and high frequency components of heart rate variability. In R-Tapex variability, high frequency (44 +/- 4 nu) was predominant over low frequency (29 +/- 4 nu). During controlled respiration, a manoeuvre associated with enhanced vagal modulation of sinus node, there was a further increase in high frequency (58 +/- 4 nu) whereas during tilt the low frequency component of R-Tapex variability became predominant (57 +/- 6 nu). In patients with a fixed atrial rate, variance was extremely low (3 +/- 0.9 ms2) and only a respiration-related high frequency component was recognizable in spectral analysis of RR and R-Tapex variabilities. This component was likely to depend upon mechanically induced changes in cardiac vector orientation. These data indicate that during sinus rhythm short-term R-Tapex interval variability is characterized by the same rhythmical components present in RR variability. However, the presence of a very low variance and of only a high frequency component in patients in whom the physiological variability of sinus node is abolished by atrial pacing. suggests that neural modulatory mechanisms do not exert a direct effect on the length of the R-Tapex interval.

Adult↗
PubMed1995

Adenosine activates cardiac sympathetic afferent fibers and potentiates the excitation induced by coronary occlusion.

Adenosine is a possible mediator of cardiac pain during myocardial ischemia; however, little is known about the influence of adenosine on cardiac sympathetic afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized, decerebrated, curarized and artificially ventilated cats, we studied the impulse activity of 20 single afferent sympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions and arterial pressure rises. All fibers increased their impulse activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold receptor characteristics. In 10 cats, epicardial applications of three different doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abolished by aminophylline, a P1 purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively, after the end of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the second occlusion initiated 30 s after the end of adenosine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by adenosine. This effect was no longer present during the last occlusion performed after 7 min. When the protocol was repeated substituting adenosine with saline (n = 5) or after i.v. administration of aminophylline (n = 5), no potentiation was observed, even though the excitatory response to coronary occlusion was preserved. These data show that adenosine can activate cardiac sympathetic afferent fibers in a dose-related manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The excitatory effects are likely to involve the P1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an algogenic code.

Adenosine↗
PubMed1995

Determination of the polar drug dimiracetam in human plasma and serum by column-switching high-performance liquid chromatography.

A sensitive and fully automated column-switching HPLC method was developed for the determination of a novel cognition enhancer, dimiracetam, in human plasma and serum. A sample of plasma was ultrafiltered and then directly injected onto a first mu Bondapak C18 column. The sample was eluted with water. The portion of the eluate (heart-cut) from this column containing the drug was selected and loaded on a second mu Bondapak C18 column and eluted with water. During the elution of the second column, the first column was automatically rinsed with water-acetonitrile (50:50, v/v) and then equilibrated for a new injection. The total analysis time for each sample was 35 min. This corresponded to a 30% decrease in analysis time compared with the time that would have been needed with a simple run with two mu Bondapak C18 columns assembled in series. Ultraviolet detection at 200 nm was used to monitor the eluate. The method was fully validated over the quantitation range 27 ng/ml-15 micrograms/ml. The applicability of the method was demonstrated by analysis of serum samples from a study performed in human healthy volunteers.

Chromatography, High Pressure Liquid↗
PubMed1995

Pure Autonomic Failure: complex abnormalities in the neural mechanisms regulating the cardiovascular system.

The aim of this study was to evaluate the sympatho-vagal interaction modulating cardiovascular function and the possible impairment of baroreceptor sensitivity in patients affected by Pure Autonomic Failure (PAF). We studied 4 patients affected by PAF and 7 controls at rest and during different levels (45 degrees, 60 degrees, 90 degrees) of head-up tilt. On a different day all subjects underwent i.v. administration of phenylephrine at dosages adequate to enhance systolic blood pressure by about 20 mmHg both at rest and during 45 degrees head-up tilt. Finally, 1.5 mg atropine was infused intravenously only in the patients. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided markers of sympathetic (low-frequency oscillations, about 0.1 Hz, LFRR) and vagal (high-frequency oscillations, about 0.25 Hz, HFRR) modulations of heart period and of sympathetic vasomotor activity (low-frequency oscillations of SAP variability, LFSAP). Baroreceptor mechanisms were quantified by means of the index alpha (calculated from the square root of the ratio between the powers of HF components of RR interval and SAP variabilities) and of the phenylephrine RR-SAP slope. Patients affected by PAF were characterized by a drastic decrease in total power of RR variability and by the absence of LFRR and LFSAP components. Moreover, HFRR, although largely predominant in its relative value, was also markedly reduced in its absolute value. Finally, the baroreceptive mechanisms appeared to be heavily impaired. In conclusion, PAF patients seem to be characterized by a complex alteration of neural mechanisms, which in addition to the signs of a sympathetic denervation include an impairment, at least functional, of the vagal modulation of heart rate.

Atropine↗
PubMed1995

Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur.

Adult↗
PubMed1995

Sympathetic predominance followed by functional denervation in the progression of chronic heart failure.

Using spectral analysis of heart rate and systolic arterial pressure variabilities, the study was set up to evaluate cardiovascular efferent autonomic modulation in patients with different degrees of chronic heart failure. We studied 30 patients with stable chronic heart failure and 15 controls of similar age. ECG, arterial blood pressure and respiratory signal were recorded at rest, during controlled respiration and during passive head-up tilting. R-R interval periods of 256-512 were analysed. Routine 2D echocardiogram and Doppler studies were also carried out. As expected, we found a decrease in the mean and variance of R-R intervals in patients with sever heart failure. In New York Heart Association (NYHA) class II patients, the power spectral pattern of R-R variability was characterized by the predominance of the low frequency component (72 +/- 3 nu), considered a marker of sympathetic activity, and by its unresponsiveness to tilting. Patients in NYHA class III also presented blunted changes in spectral components during tilting. A drastic decrease in the variance of R-R intervals (191 +/- 58 vs 1056 +/- 149 ms2 in controls) and an almost complete absence of the low frequency spectral component (8 +/- 3 nu) were present in patients in NYHA class IV. Controlled respiration, which in normal subjects decreased the low frequency component, induced changes that blunted progressively as heart failure increased. These data suggest that autonomic neural modulation and cardiovascular response to neural activity differ at different stages of the disease.

Analysis of Variance↗
PubMed1995

[Role of low-frequency neuronal activity in the medulla in the regulation of the cardiovascular system].

We recorded discharge activity of 45 single neurons located in the rostral ventrolateral medulla (n = 21), lateral tegmental field (n = 10) and caudal raphe (n = 14) nuclei in baroreceptor-denervated decerebrate cats (n = 27). Autoregressive spectral analysis was performed on neuronal activity and systolic arterial pressure (SAP). The discharges of the recorded neurons were correlated to 2- to 6 Hz oscillations or 10 Hz rhythm present in sympathetic neural discharge. A low frequency (LF) oscillation (0.12 +/- 0.02 Hz) was observed in 25 (55%) units. The same rhythmicity was found in SAP variability in 25 of 45 (55%) recordings. In 21 of these cases the LF in SAP variability was highly correlated to LF in neural activity. Moreover, 32 out of 45 (71%) neurons showed a higher rhythm (HF; 0.34 +/- 0.06 Hz) related to the ventilation rate. These data demonstrate the presence of an LF oscillation in the discharge of single medullary neurons, involved in the regulation of cardiovascular system. This LF component was similar to that detectable in the spectral analysis of SAP variability, thus supporting the hypothesis of a central origin of this rhythm, largely independent of baroreceptor input.

Analysis of Variance↗
PubMed1995

Mechanical effects of respiration and stepping on systolic arterial pressure variability during treadmill exercise.

AIM: To evaluate the changes produced by maximal dynamic exercise in the rhythmic components of systolic arterial pressure variability. PATIENTS AND METHODS: We studied seven normotensive subjects during different levels of a modified treadmill test (Bruce protocol, up to stage 4). Arterial pressure was measured directly by a high-fidelity microtip pressure transducer. Spectral analysis provided two main oscillatory components of systolic arterial pressure variability, a low-frequency component related to the sympathetic-mediated neural control of vasomotion and a high-frequency component reflecting the mechanical effects of respiration on blood pressure. RESULTS: The low-frequency component increased at the beginning of exercise and remained stable thereafter, while the high-frequency component increased progressively. A third rhythmic component (very high frequency) with a frequency higher than respiration and synchronous with the rate of the subjects' footsteps, which was undetectable on a visual inspection of analog tracings, became progressively more apparent, reaching its maximum at exercise stage 4. CONCLUSIONS: These findings emphasize the importance of high-fidelity techniques and computer analysis for the evaluation of arterial pressure variability in dynamic conditions.

Adult↗
PubMed1994

Effects of beta blockers (atenolol or metoprolol) on heart rate variability after acute myocardial infarction.

This study analyzed, with spectral techniques, the effects of atenolol or metoprolol on RR interval variability in 20 patients 4 weeks after the first uncomplicated myocardial infarction. Beta blocker-induced bradycardia was associated with a significant increase in the average 24-hour values of RR variance (from 13,886 +/- 1,479 to 16,728 +/- 1,891 ms2) and of the normalized power of the high-frequency component (from 22 +/- 1 to 28 +/- 2 normalized units), whereas the low-frequency component was greatly reduced (from 60 +/- 3 to 50 +/- 3 normalized units). When considering day and nighttime separately, the effects of both drugs were more pronounced in the daytime. In addition, a marked attenuation was observed in the circadian variation of the low-frequency component after beta blockade. As a result, the early morning increase of the spectral index of sympathetic modulation was no longer detectable. These results indicate that beta-blocker administration has important effects on RR interval variability and on its spectral components. The observed reduction in signs of sympathetic activation and the increase in vagal tone after beta blockade help to explain the beneficial effects of these drugs after myocardial infarction. However, the potential clinical relevance of the increase in RR variance remains to be established.

Atenolol↗