Alberto Galante

Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease : A randomized, controlled study

Background—Myocardial ischemia and infarction impair baroreflex sensitivity (BRS), which when depressed is predictive of future cardiac events after myocardial infarction (MI). The main objective of this study was to determine whether exercise training improves BRS in patients with coronary artery disease. Methods and Results—Ninety-seven male patients with and without a previous MI were recruited after myocardial revascularization surgery and randomized into trained (TR) or untrained (UTR) groups. TR patients underwent a residential exercise program at 85% of maximum heart rate (HRmax) consisting of 2 daily sessions 6 times a week for 2 weeks. Eighty-six patients (45 TR and 41 UTR) completed the study. BRS was assessed at baseline and at the end of the protocol by the spontaneous baroreflex method. The standard deviation of mean R-R interval (RRSD) was also assessed as a measure of heart rate variability. At baseline, there were no significant differences between TR and UTR patients in any variable. In TR patients, BRS increased from 3.0±0.3 to 5.3±0.7 ms/mm Hg (P <0.001), RRSD from 18.7±1.4 to 23.6±1.6 ms (P <0.01), and R-R interval from 792.0±15.5 to 851.3±20.5 ms (P <0.001). No significant changes occurred in UTR patients. Increases in BRS and RRSD were significant in patients either with or without a previous MI. Conclusions—Exercise training increases BRS and heart rate variability in patients with coronary artery disease. Improved cardiac autonomic function might add to the other benefits of exercise training in secondary prevention of ischemic heart disease.

Cytotoxin-Associated Gene-A–Positive Helicobacter pylori Strains Are Associated With Atherosclerotic Stroke

Background—It is uncertain whether Helicobacter pylori is associated with ischemic syndromes and whether this association is mediated by the induction of atherosclerosis. In this study, we tested the hypothesis that atherosclerotic stroke shows a selective association with virulent H pylori strains. Methods and Results—The seroprevalence of infection by H pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was assessed by ELISA in 138 patients with large-vessel stroke (group A), in 61 patients with cardioembolic stroke (group B), and in 151 healthy control subjects. The 3 groups had a similar socioeconomic status. Serum levels of C-reactive protein were also measured by ELISA. The prevalence of infection was 71% in group A, 63.9% in group B, and 70.2% in the control group (P =NS), whereas the prevalence of CagA-positive strains was higher in group A than in group B (42.8% versus 19.7%, respectively; odds ratio 3.04, 95% CI 1.43 to 6.49;P <0.001) and higher in group A than in the control group (42.8% versus 17.9%, respectively; odds ratio 4.3, 95% CI 2.12 to 8.64;P <0.001), after adjusting for main cardiovascular risk factors and social class. A trend toward a difference in C-reactive protein was observed between CagA-positive (2.00±3.43 [mean±SD] mg/dL) and CagA-negative (1.31±1.72 [mean±SD] mg/dL) patients (P =0.072, Mann-Whitney U test). Conclusions—The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.

New Site of Modification of 23S rRNA Associated with Clarithromycin Resistance of Helicobacter pylori Clinical Isolates

ABSTRACT Resistance of Helicobacter pylori to clarithromycin occurs with a prevalence ranging from 0 to 15%. This has an important clinical impact on dual and triple therapies, in which clarithromycin seems to be the better choice to achieve H. pylori eradication. In order to evaluate the possibility of new mechanisms of clarithromycin resistance, a PCR assay that amplified a portion of 23S rRNA from H. pylori isolates was used. Gastric tissue biopsy specimens from 230 consecutive patients were cultured for H. pylori isolation. Eighty-six gastric biopsy specimens yielded H. pylori-positive results, and among these 12 isolates were clarithromycin resistant. The latter were studied to detect mutations in the 23S rRNA gene. Sequence analysis of the 1,143-bp PCR product (portion of the 23S rRNA gene) did not reveal mutation such as that described at position 2142 to 2143. On the contrary, our findings show, for seven isolates, a T-to-C transition at position 2717. This mutation conferred a low level of resistance, equivalent to the MIC for the isolates, selected using the E-test as well as using the agar dilution method: 1 μg/ml. Moreover, T2717C transition is located in a highly conserved region of the 23S RNA associated with functional sites: domain VI. This fact has a strong effect on the secondary structure of the 23S RNA and on its interaction with macrolide. Mutation at position 2717 also generated an HhaI restriction site; therefore, restriction analysis of the PCR product also permits a rapid detection of resistant isolates.

Maternal Diastolic Dysfunction and Left Ventricular Geometry in Gestational Hypertension

Abstract—The objective of this study was to evaluate diastolic parameters and left ventricular geometry in gestational hypertension. Twenty-one consecutive pregnant women with gestational hypertension and 21 normotensive women matched for age and gestational age were enrolled in the third trimester of gestation. Echocardiographic and uterine color Doppler evaluations were performed. Systolic, diastolic, and mean blood pressure, total vascular resistance (TVR), and uterine resistance index were higher in hypertensive women than in control subjects (P <0.01). Left atrial function and cardiac output were significantly lower in gestational hypertension (P <0.01). Patients with gestational hypertension had longer left ventricular isovolumetric relaxation time (IVRT) (P <0.0001); lower velocity-time integral of the A wave (P <0.05) and of the diastolic pulmonary vein flow (P <0.05); and higher velocity-time integral of the reverse pulmonary vein flow (P <0.05). Systolic fraction of the pulmonary vein flow was higher in women with gestational hypertension than in control subjects (P <0.01); the difference in duration of pulmonary vein flow and A wave was closer to 0 in gestational hypertension (P <0.0001). Altered left ventricular geometry was found in 100% of hypertensive patients and in 19.05% of normotensive patients (P <0.001). IVRT, left ventricular end-systolic volume, atrial function, and uterine resistance index were directly related to TVR (P <0.01); deceleration time of the E wave showed a quadratic correlation with TVR (P <0.01). Gestational hypertension is characterized by an altered cardiac geometric pattern of concentric hypertrophy. The altered geometric pattern assessed during gestational hypertension is associated, in our study, with depressed systolic function, high TVR, altered diastolic function, and left atrial dysfunction. Deceleration time of the E wave, IVRT, and left atrial fractional area change, found in concomitance with the highest TVR, may be useful in the evaluation of cardiac function and hemodynamics present in pregnancy-induced hypertension.

Baroreflex Buffering of Sympathetic Activation During Sleep. Evidence From Autonomic Assessment of Sleep Macroarchitecture and Microarchitecture

Abstract—We examined the effects of sleep microstructure, ie, the cyclic alternating pattern (CAP), on heart rate (HR)- and blood pressure (BP)-regulating mechanisms and on baroreflex control of HR in healthy humans and tested the hypothesis that sympathetic activation occurring in CAP epochs during non-rapid eye movement (non-REM) sleep periods is buffered by the arterial baroreflex. Ten healthy males underwent polysomnography and simultaneous recording of BP, ECG, and respiration. Baroreflex sensitivity (BRS) was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate R-R interval (RRI) and BP variabilities. During overall non-REM sleep, BP decreased and RRI increased in comparison to wakefulness, with concomitant decreases in low-frequency RRI and BP oscillations and increases in high-frequency RRI oscillations. These changes were reversed during REM to wakefulness levels, with the exception of RRI. During CAP, BP increased significantly in comparison to non-CAP and did not differ from REM and wakefulness. The low-frequency component of BP variability was significantly higher during CAP than non-CAP. RRI and its low-frequency spectral component did not differ between CAP and non-CAP. BRS significantly increased during CAP in comparison to non-CAP. BRS was not different during CAP and REM and was greater during both in comparison with the awake state. Even during sleep stages, like non-REM sleep, characterized by an overall vagal predominance, phases of sustained sympathetic activation do occur that resemble that occurring during REM. Throughout the overnight sleep period, the arterial baroreflex acts to buffer surges of sympathetic activation by means of rapid changes in cardiac vagal circuits.

Sleep-related changes in baroreflex sensitivity and cardiovascular autonomic modulation.

Objective We examined the effects of the various sleep stages on baroreflex sensitivity (BRS), and heart rate and blood pressure (BP) variability, and tested the hypothesis that there is a different behavior of the baroreflex control of the sinus node in response to hypertensive and hypotensive stimuli and in relation to different cycles of the overnight sleep. Design Polygraphic sleep recordings were performed in 10 healthy males. The BP and the RR interval were continuously recorded during sleep. Methods BRS was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate the RR-interval and BP variabilities. Results During rapid eye movement (REM) sleep BRS significantly increased in response to hypertensive stimuli in comparison with non-rapid eye movement (NREM) sleep and the awake state, whereas it did not change in response to hypotensive stimuli. In the first sleep cycle, BRS significantly increased during NREM in comparison with wakefulness, whereas during REM BRS in response to hypertensive stimuli did not show significant changes as compared with the awake state and/or with NREM. During REM occurring in the sleep cycle before morning awakening, BRS showed a significant increase in response to hypertensive stimuli in comparison with both NREM and the awake state. Conclusions During sleep, arterial baroreflex modulation of the sinus node is different in response to hypotensive and hypertensive stimuli particularly during REM. Furthermore, baroreflex control of the sinus node shows a non-uniform behavior during REM occurring in different nocturnal sleep cycles. These findings suggest that the arterial baroreflex is more effective in buffering the increased sympathetic activation associated with REM at the end of sleep than in the early night.

Changes in cardiac autonomic regulation after acute lung exposure to carbon nanotubes: implications for occupational exposure

Carbon nanotubes (CNTs) are among the most relevant engineered nanomaterials (ENMs). Given the expected rise of exposure to ENMs, there is concern that they may adversely affect health of exposed people. Aim of the study was to test the hypothesis that single wall carbon nanotubes (SWCNTs) pulmonary exposure acutely affect the autonomic cardiovascular regulation in conscious rats. We studied Wistar-Kyoto rats in which a telemetry transmitter for continuous arterial pressure (AP) and heart rate (HR) recordings was surgically implanted. SWCNTs dispersed in phosphate buffer saline (PBS) or PBS alone were randomly administered intratracheally. Immediately before, and 24 hours after each instillation a 30 min AP recording was performed. The sequence analysis was performed to evaluate the baroreflex function. In the control group, PBS instillation did not induce any significant changes. At variance the SWCNT exposure induced a significant reduction of baroreflex system (BRS) (3.5 ± 0.6 versus 2.6 ± 0.40 msec/mmHg) without significant changes in the occurrence of baroreflex sequences (7.5 ± 0.47% versus 7.4 ± 0.38%). Our results show that SWCNT pulmonary exposure might affect the cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events.

Detection of clarithromycin-resistant Helicobacter pylori in stool samples.

ABSTRACT The recognition of the role of Helicobacter pylori in gastric diseases has led to the widespread use of antibiotics in the eradication of this pathogen. The most advocated therapy, triple therapy, often includes clarithromycin. It is well known that clarithromycin resistance is one of the major causes of eradication failure. The development of a rapid noninvasive technique that could easily be performed on fecal samples and that could also provide information about the antibiotic resistance of this microorganism is therefore advisable. Previous findings have demonstrated that clarithromycin resistance is due to a single point mutation in the 23S rRNA. All the mutations described have been associated with specific restriction sites, namely BsaI (A2143G), MboII (A2142C/G), and HhaI (T2717C). On this basis we have developed a new method, a seminested PCR, allowing screening for clarithromycin resistance of H. pylori directly on stool samples. This method furnished a 783-bp fragment of the 23S rRNA, which was subsequently digested by MboII, BsaI, and HhaI, in order to identify single point mutations associated with clarithromycin resistance. Of a total of 283 stool samples examined, 125 were H. pylori positive and two of them were shown to contain clarithromycin-resistant strains due to the presence of a mutation at position 2717, whereas no PCR products contained mutations at position 2142 or 2143. In order to evaluate the reliability of the new system, we compared the results of restriction analysis of the PCR products with the MICs shown by the H. pylori isolates by culturing gastric biopsies from the same patients.

Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score

BackgroundThe aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization.MethodsThis was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient.ResultsMR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively).In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79.ConclusionsThe present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient’s care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs.

Spontaneous baroreflex modulation of heart rate and heart rate variability during orthostatic stress in tetraplegics and healthy subjects.

Objective This study was addressed to investigate the contribution of vagal and sympathetic mechanisms to the genesis of low-frequency (LF) oscillations of RR-interval. Design To this aim, we utilized the pathophysiological model of tetraplegics, who have intact vagal afferent and efferent pathways of the baroreceptor reflex arc but interrupted medullary-spinal sympathetic pathways. Methods We studied nine complete, traumatic, tetraplegics (C4–C7, TET) and 10 normally healthy subjects (NR) at rest and during physiological baroreceptors unloading induced by 70 ° head-up tilt. Autoregressive power spectral analysis was used to investigate RR-interval and systolic arterial pressure (SAP) variabilities. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. Results Both at-rest and during-tilt LF and high frequency (HF) components were detected in RR-interval of NR, whereas in TET only the HF component was observed in both conditions (with one exception). Baroreflex sensitivity (BRS) did not significantly differ between TET and NR at rest, and underwent a significant and similar decrease during tilt in both groups, being accompanied in NR by a significant increase in LF relative power. Spectral analysis of SAP provided results similar to RR-interval. Tilt also slowed the centre frequency of the LF components of RR-interval and SAP. Conclusions During unperturbed physiological conditions, a change in efferent vagal activity to the heart from baroreflex stimulation by spontaneous arterial pressure changes, is unlikely to contribute on its own to the genesis of LF heart period oscillations in humans who lack the ability to modulate sympathetic nerve traffic to the heart. However, the possibility that a baroreflex modulation of LF oscillations require an intact sympathetic control should be carefully considered.