Whole-body bioelectrical impedance analysis in patients with chronic heart failure: reproducibility of the method and effects of body side.

BACKGROUND: Fluid imbalance and malnutrition have an important role in the clinical setting of chronic heart failure (CHF). Recently, tetrapolar bioelectrical impedance analysis has been suggested as an attractive method which may be used in the clinical assessment of the body composition. The aim of this study was to determine the effects of body side on whole bioelectrical impedance analysis parameters and test-retest reliability, prior to its use in a large cohort of patients. METHODS: In 114 consecutive patients with CHF (mean age 65 +/- 10 years, left ventricular ejection fraction 31 +/- 9%, NYHA functional class 2.6 +/- 0.9) we measured the total body resistance, the reactance and the derived angle phase using a single-frequency (50 KHz) tetrapolar plethysmograph device. The evaluations were performed on the left and right sides of the body, in a random order, on two different occasions 30 min apart. The effects of body side were analyzed by the Student's t-test and the test-retest reliability was computed by using the coefficient of variation and intraclass correlation coefficient. RESULTS: In both evaluations, the mean resistance value of the right side was significantly lower (almost 10 ohms) than that of the left side, the reactance was not different, and as a consequence the angle phase was significantly higher (almost 0.1 degrees) in the right than in the left side. The test-retest reliability for all the measurements considered was very high (the intraclass correlation coefficient ranged from 0.95 to 0.99 and the coefficient of variation from 1.7 to 4.3%). CONCLUSIONS: In CHF, the body side is important for the whole-body assessment of the resistance and the angle phase, but not for reactance. In addition, all these measurements are characterized by an excellent test-retest reliability and, consequently, do not necessitate a substantial increase in the sample size for the detection of small differences in experimental studies.

[Cardiopulmonary sensitivity and chemosensitivity]. / Sensibilità cardiopolmonare e chemosensibilità.

The autonomic control of the cardiovascular system plays an important role in maintaining the arterial pressure at the levels necessary for adequate tissue perfusion. In cardiovascular diseases, the impairment of the basic reflex mechanisms that are responsible for the moment-to-moment regulation could increase sympathetic activity and is correlated with an adverse outcome. The objective of the present review was to provide information about the methodological aspects exploring cardiopulmonary and chemoreceptor reflexes. Different techniques are available and all of them include assessment of reflexes through the activation or deactivation of either the cardiopulmonary baroreceptors or chemoreceptors. Intravenous saline load, head-down tilt, passive legs raising, head-out water immersion and the application of a lower body positive pressure are the principal methods utilized for activating cardiopulmonary baroreceptors; on the contrary deactivation could be achieved by acutely induced hypovolemia by furosemide or blood donation, inflation of a congestion cuff on the thighs or application of a negative pressure on the lower body. The transient exposure to a hypoxic or a hypercapnic gas mixture is frequently used to determine the peripheral and central chemoreflexes, respectively. The reflexes are quantified by the gain between output (i.e. heart rate, sympathetic activity, vascular resistance, ventilation) and input (oxygen saturation, end-tidal CO2 or changes in central venous pressure). One important limitation in assessing the cardiopulmonary baroreflex by using currently available techniques is that the involvement of the arterial baroreflex cannot be avoided. In addition, chemoreflexes cannot be interpreted unless the breathing rate is controlled. To date, several techniques are available for the quantification of cardiopulmonary baroreceptor and chemoreceptor reflexes and could provide new information on the abnormal autonomic mechanisms contributing to the pathophysiology of several cardiovascular diseases.

Depression but not anxiety influences the autonomic control of heart rate after myocardial infarction.

AIMS: It has been previously hypothesized that the adverse outcome observed in depressed patients after myocardial infarction might be due to an imbalance in autonomic nervous system activity. The aim of this study was to define the role of depressive and anxious symptoms in influencing autonomic control of heart rate after myocardial infarction. METHODS AND RESULTS: The SD of RR intervals, baroreflex sensitivity, and depression and anxiety (Zung's scales) were assessed before discharge in 103 patients with acute myocardial infarction; 32 were found to be depressed. Among the patients who were not taking beta-blockers, those with depression had significantly lower SDs of RR intervals and baroreflex sensitivity than did those without depression (96.3 +/- 22.2 ms vs 119.5 +/- 37.7 ms, P =.016; 8.6 +/- 6.2 ms vs 11.8 +/- 6.5 ms/mm Hg, P =.01, respectively). No differences were found when anxiety was considered or when beta-blockers were given. Among the patients not taking beta-blockers, there was a significant correlation between depression levels and both the SD of RR intervals (r = -0.47) and baroreflex sensitivity (r = -0.40). CONCLUSIONS: In patients with myocardial infarction, depression but not anxiety negatively influences autonomic control of heart rate. Beta-blockers modify these influences.

Effect of intermittent subdiastolic pressure in thigh cuffs on human arterial baroreflex.

BACKGROUND: We investigated the effects of subdiastolic variations of the pressure inside the thigh cuffs on cardiovascular oscillations and arterial baroreflex sensitivity in humans. METHODS: During 10 min of controlled breathing at low (0.1 Hz) and high (0.25 Hz) frequencies, 30 healthy subjects underwent variations of the pressure inside the thigh cuffs (from 0 to 40 mmHg) at 0.25 and 0.1 Hz respectively; the periods of controlled breathing without cuff pressure modulation were used as a control. The frequency responses of cardiovascular signals were assessed using spectral analysis, and baroreflex sensitivity by the sequence method. RESULTS: Cuff pressure modulation at 0.25 Hz did not affect the RR interval, arterial pressure, or baroreflex sensitivity; at 0.1 Hz it did not change the RR interval and arterial pressure, but engaged (0.76 +/- 0.2 of coherence) and increased the low frequency oscillations of the RR interval (from 5.6 +/- 1 to 6.1 +/- 0.9 ln ms2, p < 0.05) and improved baroreflex sensitivity by 25% (from 14.2 +/- 9 to 17.7 +/- 10 ms/mmHg, p < 0.01). CONCLUSIONS: Subdiastolic thigh cuff pressure modulation at 0.1 Hz improved the low frequency oscillations of heart rate and baroreflex sensitivity. This approach represents a new and simple non-pharmacological strategy for acutely improving baroreflex sensitivity in humans.

Influence of hydrophilic and lipophilic beta-blockers on heart rate, ventricular repolarization and their interrelationship in normal subjects.

BACKGROUND: It has been hypothesized that hydrophilic and lipophilic beta-blockers have different antiarrhythmic properties because only the latter seem to reduce the rate of sudden death in post-myocardial infarction patients as well as animal models which seem to be independent of their effect on autonomic nervous system modulation. The aim of this study was to evaluate the different effects of a hydrophilic (nadolol) and lipophilic (metoprolol) beta-blocker on ventricular repolarization in normal subjects. METHODS: Seventeen normal subjects entered this randomized, single-blind cross-over study designed to compare the effects of nadolol (80 mg/day) and slow-release metoprolol (200 mg/day) on dynamic ventricular repolarization. The RR intervals, the QT evaluated at the apex (QT apex) and at the end (QT end) of the T wave before and after correction for heart rate, the standard deviation of QT apex and QT end, and the slope of the QT/RR linear relationship (QTa-slope and QTe-slope) were studied using the ELATEC system (ELA Medical, Mountrouge, France), and an evaluation was made of their reproducibility and the effects of each beta-blocker. RESULTS: The most reproducible parameters were QT apex, corrected QT apex and the QTe-slope. Nadolol was associated with a greater adrenergic blockade than metoprolol (lengthening of RR interval +25 +/- 7 and +17 +/- 8% respectively, p = 0.0003) and a lower effect on ventricular repolarization (reduction of corrected QT apex -0.6 +/- 3 and -2.5 +/- 2.1% respectively, p < 0.01; reduction of QTe-slope -5 +/- 16 and -15 +/- 15% respectively, p = 0.03). CONCLUSIONS: At the dosages used in the study, metoprolol showed lower adrenergic blockade but greater effect on ventricular repolarization than nadolol.

Age effect on phase relations between respiratory oscillations of the RR interval and systolic pressure.

Spectral analysis may allow the evaluation of (baroreflex) gain and phase between the RR interval and systolic pressure oscillations synchronous with respiration but, unlike baroreflex gain, the determinants of phase are not completely understood. We evaluated the correlates of spectral phase in 92 healthy subjects (44 men) aged 10-80 years. To do so, the cardiorespiratory signals during paced breathing at 16 breaths/min were continuously recorded and analyzed. In addition, respiratory sinus arrhythmia and baroreflex gain (two indices of cardiac vagal activity) and phase were calculated by using an autoregressive spectral technique. At univariate analysis, the phase correlated with age (r = 0.48, P < 0.001), the RR interval (r = 0.32, P < 0.01), respiratory sinus arrhythmia (r = -0.3, P < 0.01), baroreflex gain (r = -0.29, P < 0.01), and body mass index (r = 0.25, P < 0.05). At multivariate analysis, age was the most important physiological correlate of phase, accounting for 23% of interindividual phase variation. Cardiac vagal activity measures (which were higher in women than men) and the RR interval were also significant independent correlates of phase. We conclude that in addition to the RR interval and cardiac vagal activity, age has a significant impact on the phase relationship between respiratory related oscillations of the RR interval and systolic blood pressure. This spectral measure may contain additional information concerning the mechanisms that influence cardiovascular rhythms.

Respiratory systolic pressure variability during atrial fibrillation and sinus rhythm.

Previous studies have found that respiratory variations of ventricular response in atrial fibrillation are infrequent and inconsistent. This asynchrony between heart rate and respiration may characterize the physiological mechanisms coupling heart rate and systolic blood pressure oscillations in the respiratory band. The aim of this study was to evaluate whether synchronous variations in systolic blood pressure and respiration depend on a simultaneous change in heart rate. Univariate and bivariate spectral analyses were made of the R-R interval, systolic blood pressure, and respiratory signals during controlled respiration (16 breaths/min) in 24 patients with atrial fibrillation before and after efficacious electrical cardioversion and in 24 age- and sex-matched control subjects. During atrial fibrillation, the spectral coherence between respiration and heart rate was low (0.18+/-0.03), but there was a high level of coherence between respiration and systolic blood pressure (0.67+/-0.05). After cardioversion, the coherence between respiration and heart rate increased to 0.86+/-0.04, whereas the geometric mean values of the concomitant respiratory systolic blood pressure oscillations decreased by 72% (from 21.1 to 5.9 mm Hg(2), P<0.001), which was similar to that observed in the control group (5. 7 mm Hg(2)). These results confirm the inconsistent effect of respiration on heart rate response during atrial fibrillation and demonstrate that respiratory sinus arrhythmia is not a prerequisite for systolic blood pressure oscillations but may play an antioscillatory role in respiratory systolic blood pressure variability, which is probably mediated by arterial baroreflex mechanisms.

Diastolic dysfunction and baroreflex sensitivity in hypertension.

The determinants of diastolic dysfunction in patients with systemic hypertension are not completely known. To evaluate the possible role of age, arterial blood pressure, and baroreflex heart rate response impairment in causing diastolic dysfunction, we studied 61 patients (42 male; mean+/-SD age, 43.9+/-12 years) with newly recognized and therefore previously untreated systemic hypertension. Diastolic dysfunction was evaluated by means of Doppler echocardiography (and diagnosed as such when the early to atrial peak velocity ratio corrected to heart rate was <1), arterial blood pressure by 24-hour ambulatory monitoring, and baroreflex heart rate response by means of the spectral technique (alpha index) during paced (0.27 Hz) and spontaneous breathing (in a supine position and during tilt). Nineteen patients had diastolic dysfunction, the most powerful predictor of which was age (r=-0.63, P<0.001). The patients with diastolic dysfunction had significantly lower values for spectral baroreflex gain in the high-frequency band than those without (5.2+/-3 versus 8.4+/-5 ms/mm Hg during paced breathing, P<0.05; 7. 4+/-4 versus 13.3+/-7 ms/mm Hg in a supine position, P<0.05; 4.3+/-4 versus 5+/-2 ms/mm Hg during tilt, P

Assessment of cardiac vagal activity in patients with hyperthyroidism.

Previous studies suggested that in patients with hyperthyroidism an autonomic imbalance and in particular a lower than normal vagal activity might be present. To verify this hypothesis we have evaluated the respiratory sinus arrhythmia (RSA, a measure of cardiac vagal activity) in ten hyperthyroid patients and in ten normal subjects. RSA was calculated from the power of the spectral component of the heart rate variability in high frequency band (HF-RR) during both spontaneous (supine and passive head-up tilt) and controlled breathing (supine). During controlled breathing the phase relation between heart rate and respiratory has been computed. The hyperthyroid patients showed a higher heart rate in all three conditions (P<0.001) and higher spontaneous respiratory rate in supine position (centered frequency of HF-RR: 0.342+/-0.015 vs 0.262+/-0.016 Hz; P<0.001). No difference was found in hyperthyroid patients compared to controls in terms of the HF-RR power in normalized units both during spontaneous breathing (supine, 43+/-8.3 vs 39.7+/-6.7%; tilt 18.8+/-5.9 vs 19.3 vs 4.1%; mean+/-SE) and controlled breathing (45.4+/-7.1 vs 48.9+/-6.9%). No difference was found also in terms of the phase relationship between the heart rate and the respiratory signals (77.5+/-32.3 vs 77.5+/-28.1, degrees). Hyperthyroid patients seem not to have an impaired cardiac vagal activity.

Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon.

OBJECTIVE: The aims of this study were to determine the relationships between oscillations in systolic blood pressure and heart period at different breathing frequencies and to investigate the role of sympathetic contribution to this relationship. METHODS: Fourteen healthy volunteers underwent three randomized periods of controlled breathing at 6, 10 and 16 breaths/min. ECG (RR), respiratory signal (RESP) and systolic blood pressure (SBP) were continuously recorded. The component of RR and SBP oscillations related to respiration (RRResp and SBPResp) was defined by means of uni- and bivariate spectral analysis. The squared coherence (K2) and phase between RR and RESP, and RR and SBP (RR-SBP) were also assessed. When the K2 of RR-SBP in the respiratory band was > 0.5, we considered the phase and calculated the closed-loop gain between the two signals. Seven subjects were also studied after chronic metoprolol treatment. RESULTS: Although the mean values of RR and SBP did not differ between the three periods of breathing, the higher the respiratory rate, the smaller the RRResp and SBPResp. The phase was always negative (SBPResp changes preceded RRResp changes), thus suggesting a baroreflex link. The higher the respiratory rate, the lower the gain and phase. Pharmacological beta-adrenoceptor blockade increased the gain and shifted the phase, but the relationships found at baseline between the respiratory rate and both the gain and phase remained unchanged. CONCLUSIONS: The effect of breath rate on the relationship between heart rate and systolic pressure variabilities is a frequency-dependent phenomenon that is also independent of the sympathetic drive.

[Double-blind randomized placebo-controlled study of the effects of slow release and immediate release forms of propafenone in patients ventricular extrasystole symptoms]. / Studio in doppio cieco, randomizzato, controllato con placebo, degli effetti di due formulazioni di propafenone a rilascio ritardato e di quello a rilascio immediato sulle extrasistoli ventricolari sintomatiche. Gruppo degli Investigatori.

This is a multicenter, randomized, double-blind, placebo-controlled, cross-over and double-dummy study aimed at testing the efficacy and tolerability of two slow-release propafenone (Pr SR) preparations and compare them with the effect of instant release propafenone (Pr IR). The study was performed in 83 patients with frequent (> 30 premature ventricular contractions/hour) and stable (< 35% variability in two 24-hour ECG monitoring periods) symptomatic premature ventricular contractions. Patients were preliminarily studied in wash-out from antiarrhythmic drugs. After a period of placebo administration, all patients underwent three consecutive periods during which they received Pr IR at the dosage of 150 mg x 3, Pr SR at the dosage of 225 mg x 2, Pr SR at the dosage of 325 mg x 2. The periods lasted 10-14 days each and the sequence was randomly assigned. Twenty-four-hour ECG monitoring periods were obtained at the end of the placebo as well as at the last day of each treatment period. Treatment efficacy was evaluated by intention to treat analysis in 80 patients and by protocol in 61. Treatment was considered efficacious when premature ventricular contraction reduction > or = 75%, couplet reduction > or = 90% and non sustained ventricular tachycardias were completely suppressed. Pr IR 150 mg x 3 was efficacious in 42% of patients, Pr SR 325 mg x 2 in 45.9% and Pr SR 225 mg x 2 in 32%. Tolerability was considered good in the majority of patients. These results show that among the different types studied, Pr SR 325 mg x 2 should be considered the treatment of choice for premature ventricular contractions.

Beta-blocker effects on respiratory sinus arrhythmia and baroreflex gain in normal subjects.

STUDY OBJECTIVE: The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. PARTICIPANTS AND DESIGN: Twenty normal subjects (28+/-2 years old) were randomized to receive a hydrophilic (nadolol) beta-blocker, a lipophilic (metoprolol) beta-blocker, and placebo. MEASUREMENTS: After 1 week of therapy, a spectral analysis was made of the variability in heart rate and systolic BP during controlled breathing at 16 breaths/min. The high-frequency component was calculated for the RR interval (measure of RSA) and systolic pressure, and the squared coherence and phase functions were assessed between RR and systolic pressure fluctuations in the respiratory band; a negative phase means that RR changes follow systolic pressure changes. The gain in the relationship between the two signal fluctuations was also calculated. RESULTS: Both beta-blockers increased the mean (+/-SD) RR interval (placebo=808+/-21, nadolol=1,054+/-30, metoprolol=1,031+/-27 ms; p<0.0001), RSA (placebo=542, nadolol=1,177, metoprolol=1,316 ms2; p=0.002), and the gain (placebo=13.6+/-1.5, nadolol=21.9+/-2.8, metoprolol=24.5+/-3.6 ms/mm Hg; p<0.002), and both modified the phase function (placebo=-21.1+/-5.3, nadolol=-1.8+/-4.9, metoprolol=-2.9+/-4.2 degree; p<0.0001). No difference was found between nadolol and metoprolol. CONCLUSIONS: Chronic beta-adrenergic blockade enhanced both RSA and baroreflex gain and reduced the phase between the RR interval and systolic pressure oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.

Different trends of changes in heart rate variability in patients with anterior and inferior acute myocardial infarction.

Modifications in heart rate variability (HRV) parameters occur after acute myocardial infarction. The aim of this study was to evaluate the trend of HRV change during the acute phase and the first month after myocardial infarction, and establish whether they were affected by the anterior or inferior location of the infarction. The time-domain HRV measures of 59 patients with a first uncomplicated acute myocardial infarction were computed from 24-hour ECG recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and the root mean square successive difference of NN intervals (RMSSD) were lower in the patients with anterior myocardial infarction. Although the parameters were similar in all of the patients at day 28, their behavior over time was different (P = 0.01): the SDNN in the patients with inferior myocardial infarction had decreased to the values found in anterior myocardial infarction patients by day 2 but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had diminished in both groups by day 2, but at day 10, had increased in the patients with anterior, but not in those with inferior myocardial infarction. These findings suggest that (1) in the very early phase of myocardial infarction, HRV is different in the two locations, (2) during the first hours of myocardial infarction patients with inferior location showed a greater vagal activity than patients with anterior location that became lower at day 10, and (3) the recovery of HRV is an early phenomenon in both groups, being already evident by the second week after myocardial infarction.

Comparison between noninvasive indices of baroreceptor sensitivity and the phenylephrine method in post-myocardial infarction patients.

BACKGROUND: Depressed baroreflex sensitivity obtained by means of a phenylephrine test plays a prognostic role in patients with a previous myocardial infarction. Our purpose was to evaluate the correlation and agreement between the baroreflex sensitivity obtained with phenylephrine and that obtained by two noninvasive methods: the alpha-index and sequence analysis. METHODS AND RESULTS: The alpha-index was measured by means of the spectral analysis of RR and systolic blood pressure variabilities in both the high- and low-frequency bands; sequences were identified from simultaneously recorded time series in which the RR and systolic blood pressure concurrently increased or decreased. Noninvasive baroreflex sensitivity tests were performed during both spontaneous and controlled respiration. Fifty-two consecutive patients with recent myocardial infarction underwent the analyses. Although the correlations between phenylephrine and either of the noninvasive methods were always significant, those found during controlled respiration had the highest r values (r=.70). However, the limits of agreement calculated by means of the Bland and Altman method were wide for both noninvasive methods. CONCLUSIONS: The results obtained by means of noninvasive baroreflex sensitivity assessments should not be used in clinical practice as an alternative to those obtained by the phenylephrine method.

Effects of hydrophilic and lipophilic beta-blockers on heart rate variability and baroreflex sensitivity in normal subjects.

To evaluate the effect of a hydrophilic and a lipophilic beta-blocker on the autonomic nervous system, 20 normal subjects were studied under baseline conditions and 7 days after being randomly assigned to metoprolol (200 mg/day), nadolol (80 mg/day), and placebo. Under each condition, the time-domain parameters were analyzed by means of 24-hour ECG monitoring and the frequency-domain parameters by means of the autoregressive method using 10-minute ECGs during rest, controlled respiration, and after a head-up tilt test. The alpha index (the gain in the relationship between the RR period and systolic arterial pressure variability) was also calculated. Both nadolol and metoprolol significantly increased all of the time-domain parameters except the standard deviation of the RH intervals; they also modified the frequency-domain parameters. Both blunted the significant reduction in the high frequency (HF) component and alpha index during tilt. In normal subjects, hydrophilic and lipophilic beta-blockers similarly modify the time- and frequency-domain parameters that are particularly evident when high sympathetic tone is present (during daytime and tilt). The value of the alpha index was increased by both beta-blockers in the HF, but not in the low frequency band; this difference might be due to the fact that the former is a measure of the vagal component of the baroreflex control and the latter a measure of the sympathetic component. The effects of hydrophilic and lipophilic beta-blockers on the time- and frequency-domain parameters of heart rate variability are similar.

Heart rate dependency of premature ventricular contractions. Correlation between electrocardiographic monitoring and exercise-related patterns.

AIMS: The identification of the response of ventricular arrhythmias to exercise testing could provide important information in the clinical setting but is difficult to obtain as no definite criteria are available. The aim of this study was to evaluate whether analysis of spontaneous heart rate dependency of premature ventricular contractions evaluated by means of 24 h electrocardiographic monitoring is capable of predicting their behaviour during exercise. METHODS AND RESULTS: One hundred and twenty-six patients (49 +/- 16 years) with frequent (> 30 h) premature ventricular contractions underwent 24 h electrocardiographic monitoring in order to evaluate the relationship between arrhythmias and heart rate, and an exercise test in order to evaluate the behaviour of the arrhythmias. On the basis of the incidence of premature ventricular contractions at different cardiac cycle lengths found at electrocardiographic monitoring, three groups of patients were identified: 34 with a tachycardia-enhanced pattern (the shorter the cycle length the higher the incidence of arrhythmias); 32 with a bradycardia-enhanced pattern (the longer the cycle length the higher the incidence of arrhythmias); and 60 patients with an indifferent pattern (no relationship). During the exercise test, the number of premature ventricular contractions/min at maximal effort in comparison with baseline increased in patients with a tachycardia-enhanced pattern (couplets or runs appeared in 10), decreased in those with a bradycardia-enhanced pattern and did not change in those with an indifferent pattern. The positive predictive accuracy of the tachycardia-enhanced pattern in predicting an increase in premature ventricular contractions > 100% at maximal effort was 78%. CONCLUSION: Identification of spontaneous behaviour between the incidence of premature ventricular contractions and the length of the preceding cardiac cycle may predict the behaviour of arrhythmias during exercise.

Dependency of premature ventricular contractions on heart rate.

To identify a method for characterizing the dynamic behavior of ventricular arrhythmias at different heart rates, 201 consecutive patients with frequent premature ventricular contractions (PVCs) underwent two 24-hour electrocardiographic monitoring periods. The percentage of PVCs for each cycle length was calculated and then analyzed by linear regression analysis. On the basis of the significance of the p value, and the positive or negative value of the slope, we identified three trends: a tachycardia-enhanced pattern (p < 0.01, slope negative), a bradycardia-enhanced pattern (p < 0.01, slope positive), and an indifferent pattern (p > 0.01). During the first monitoring period, a tachycardia-enhanced pattern was present in 56 patients (28%), a bradycardia-enhanced pattern was present in 49 patients (24%), and an indifferent pattern was present in 96 patients (48%). This relationship was reproducible in 41 of the patients with a tachycardia-enhanced pattern (73%), in 29 of the patients with a bradycardia-enhanced pattern (59%), and in 70 patients with an indifferent pattern (72%). In conclusion, it is possible to identify a spontaneous trend between the incidence of ventricular arrhythmias and the length of the preceding cardiac cycle that seems to remain stable over time.

[The effects of chronic beta-blocker administration on respiratory sinus arrhythmia]. / Effetti della somministrazione cronica di betabloccanti sull'aritmia sinusale respiratoria.

The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. In some studies in which an increased RSA was reported, central vagotonic activity has been proposed. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. Twenty normal subjects (mean age 28 +/- 2 years) were randomized to receive a hydrophilic (nadolol, N), a lipophilic (metoprolol, M) beta-blocker and placebo (PL). After 1 week of therapy a spectral analysis was made of the variability in heart rate and systolic blood pressure (SBP) while they controlled their breathing at 16 breaths/min for a period of 5 min. The high frequency component was calculated for the RR interval (HF-RR, RSA measure) and SBP (HF-SBP), and the squared coherence (K2) and phase functions (phi HF) were assessed between RR and SBP fluctuations in the respiratory band (RR-SBP); a negative phi HF means that RR changes follow SBP changes. The alpha HF (an index of the baroreflex gain) was also calculated. Both beta-blockers increased the mean RR interval (PL 808 +/- 21, N 1054 +/- 30, M 1031 +/- 27 ms; p < 0.0001), HF-RR (PL 6.3 +/- 0.3, N 7.1 +/- 0.3, M 7.2 +/- 0.3 ln-ms2; p = 0.002) and alpha HF (PL 13.6 +/- 1.5, N 21.9 +/- 2.8, M 24.5 +/- 3.6 ms/mmHg; p < 0.002), and both modified phi HF (PL -0.23 +/- 0.05, N -0.02 +/- 0.05, M -0.03 +/- 0.04 s; p < 0.0001). No difference was found between N and M. Chronic beta-adrenergic blockade enhanced RSA and baroreflex gain and reduced the phase between the RR interval and SBP oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.