Publications by authors named "Jacopo M Legramante"

19 Publications

  • Page 1 of 1

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department.

Expert Rev Mol Diagn 2021 Mar 29:1-8. Epub 2021 Mar 29.

Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.

Introduction: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature.

Areas Covered: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting.

Expert Opinion: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.
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http://dx.doi.org/10.1080/14737159.2021.1902312DOI Listing
March 2021

Complete blood count might help to identify subjects with high probability of testing positive to SARS-CoV-2.

Clin Med (Lond) 2020 07 2;20(4):e114-e119. Epub 2020 Jul 2.

Emergency Department, Tor Vergata University Hospital, Rome, Italy.

The SARS-CoV-2 pandemic has dramatically increased the workload for health systems and a consequent need to optimise resources has arisen, including the selection of patients for swab tests. We retrospectively reviewed consecutive patients presenting to the emergency department with symptoms suggestive of COVID-19 and undergoing swab tests for SARS-CoV-2. Complete blood counts (CBCs) were analysed looking for predictors of test positivity. Eight significant predictors were identified and used to build a 'complete' CBC score with a discriminatory power for COVID-19 diagnosis of AUC 92% (p<0.0001). When looking at the weight of individual variables, mean corpuscular volume (MCV), age, platelets and eosinophils (MAPE: MCV ≤90 fL, 65 points; age ≥45 years, 100 points; platelets ≤180×103/μL, 73 points; eosinophils <0.01/μL, 94 points) gave the highest contribution and were used to build a 'simplified' MAPE score with a discriminatory power of AUC 88%. By setting the cut-off MAPE score at ≥173 points, sensitivity and specificity for COVID-19 diagnosis were 83% and 82%, respectively, and the actual test positivity rate was 60% as compared to 6% of patients with MAPE score <173 points (odds ratio 23.04, 95% confidence interval [CI] 9.1-58.3, p-value <0.0001). In conclusion, CBC-based scores have potential for optimising the SARS-CoV-2 testing process: if these findings are confirmed in the future, swab tests may be waived for subjects with low score and uncertain symptoms, while they may be considered for asymptomatic or oligosymptomatic patients with high scores.
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http://dx.doi.org/10.7861/clinmed.2020-0373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385801PMC
July 2020

How biomarkers can improve pneumonia diagnosis and prognosis: procalcitonin and mid-regional-pro-adrenomedullin.

Biomark Med 2020 05 28;14(7):549-562. Epub 2020 May 28.

Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Italy.

The diagnostic and prognostic role of procalcitonin (PCT) and mid-regional-pro-adrenomedullin (MR-proADM) were investigated in patients with pneumonia. A total of 168 and 77 patients with pneumonia enrolled in two different hospital settings, an internal medicine unit and an emergency unit were included in the study. PCT and MR-proADM plasma concentrations and pneumonia severity index score were measured. Median values were compared by Mann-Whitney's test. Receiver operating characteristic analysis and rank correlation were used to define the diagnostic and prognostic accuracy. PCT confirmed the diagnostic role at values 0.08-0.10 ng/ml and MR-proADM the prognostic role for severe pneumonia. Significant correlation (p < 0.0001) between MR-proADM and pneumonia severity index score indicated expression of pneumonia severity. This combination of biomarkers presents a high positive predictive value in pneumonia diagnosis and prognosis.
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http://dx.doi.org/10.2217/bmm-2019-0414DOI Listing
May 2020

The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study.

Crit Care 2019 Feb 8;23(1):40. Epub 2019 Feb 8.

Emergency Department, Instituto de Investigación Sanitaria (IdISSC), Hospital Clínico San Carlos, Madrid, Spain.

Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need.

Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days.

Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities.

Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.
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http://dx.doi.org/10.1186/s13054-019-2329-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368690PMC
February 2019

2-hydroxycaproate predicts cardiovascular mortality in patients with atherosclerotic disease.

Atherosclerosis 2018 10 12;277:179-185. Epub 2018 Jun 12.

Department of Systems Medicine, University of Rome Tor Vergata, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy. Electronic address:

Background And Aims: We aimed to identify novel biomarkers for cardiovascular mortality through a non-targeted metabolomics approach in patients with established atherosclerotic disease from the Tor Vergata Atherosclerosis Registry (TVAR).

Methods: We compared the serum baseline metabolome of 19 patients with atherosclerosis suffering from cardiovascular death during follow-up with the baseline serum metabolome of 20 control patients matched for age, gender, body mass index (BMI) and atherosclerotic disease status, who survived during the observation period.

Results: Three metabolites were significantly different in the cardiovascular mortality (CVM) group compared to controls: 2-hydroxycaproate, gluconate and sorbitol. 2-hydroxycaproate (otherwise known as alpha hydroxy caproate) was also significantly correlated with time to death. The metabolites performed better when combined together rather than singularly on the identification of CVM status.

Conclusions: Our analysis led to identify few metabolites potentially amenable of translation into the clinical practice as biomarkers for specific metabolic changes in the cardiovascular system in patients with established atherosclerotic disease.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.014DOI Listing
October 2018

Frequent Use of Emergency Departments by the Elderly Population When Continuing Care Is Not Well Established.

PLoS One 2016 14;11(12):e0165939. Epub 2016 Dec 14.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Introduction: The elderly, who suffer from multiple chronic diseases, represent a substantial proportion of Emergency Department (ED) frequent users, thus contributing to ED overcrowding, although they could benefit from other health care facilities, if those were available. The aim of this study was to evaluate and characterize hospital visits of older patients (age 65 or greater) to the ED of a university teaching hospital in Rome from the 1st of January to the 31st of December 2014, in order to identify clinical and social characteristics potentially associated with "elderly frequent users".

Material And Methods: A retrospective study was performed during the calendar year 2014 (1st January 2014 - 31st December 2014) analyzing all ED admissions to the University Hospital of Rome Tor Vergata. Variables collected included age, triage code, arrival data, discharge diagnosis, and visit outcome. We performed a risk analysis using univariate binary logistic regression models.

Results: A total number of 38,016 patients accessed the ED, generating 46,820 accesses during the study period, with an average of 1.23 accesses for patient. The elderly population represented a quarter of the total ED population and had an increased risk of frequent use (OR 1.5: CI 1.4-1.7) and hospitalization (OR 3.8: CI 3.7-4). Moreover, they showed a greater diagnostic complexity, as demonstrated by the higher incidence of yellow and red priority codes compared to other ED populations (OR 3.1: CI 2.9-3.2).

Discussion: Older patients presented clinical and social characteristics related to the definition of "elderly frail frequent users". The fact that a larger number of hospitalizations occurred in such patients is indirect evidence of frailty in this specific population, suggesting that hospital admissions may be an inappropriate response to frailty, especially when continued care is not established.

Conclusion: Enhancement of continuity of care, establishment of a tracking system for those who are at greater risk of visiting the ED and evaluating fragile individuals should be the highest priority in addressing ED frequent usage by the elderly.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165939PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156362PMC
July 2017

Cardiovascular and hemodynamic responses to adapted physical exercises in very old adults.

Aging Clin Exp Res 2017 Jun 20;29(3):419-426. Epub 2016 Jun 20.

Dipartimento di Emergenza, Policlinico di Tor Vergata, Università "Tor Vergata", viale Oxford 81, 00133, Rome, Italy.

Background: Aging is characterized by a physiological reduction in physical activity, which is inversely correlated with survival.

Aims: Aim of the present study is to evaluate the cardiovascular, central hemodynamic and autonomic responses to a single bout of adapted physical exercise in octogenarian subjects.

Methods: We studied cardiovascular, hemodynamic and autonomic responses to adapted physical activity in 33 subjects by a noninvasive methodology (Nexfin, Edwards Lifesciences Corporation).

Results: Our octogenarians presented a significant increase in mean arterial pressure (p < 0.01) and heart rate (p < 0.005) in response to exercise, while both are reduced during the early recovery phase. Central hemodynamic showed a significant increase in stroke volume (p < 0.05), cardiac output (p < 0.01) and left ventricle contractility index (p < 0.01), whereas systemic vascular resistance showed a significant decrease (p < 0.001). We found a reduction in baroreflex control of the sinus node during exercise.

Discussion: Our data demonstrate that in very old people adapted physical activity is able to activate cardiovascular system and to induce a postexercise hypotension similarly to adults. The baroreflex control of sinus node seems to contribute in the physiological mechanism of these cardiovascular adaptations.

Conclusions: In very old people, physical activity induces cardiovascular and hemodynamic responses not significantly different from those induced in adult even though some cautions particularly in the early recovery phase after exercise should be exercised.
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http://dx.doi.org/10.1007/s40520-016-0598-2DOI Listing
June 2017

Disparities in management of new-onset atrial fibrillation in the emergency department despite adherence to the current guidelines: data from a large metropolitan area.

Intern Emerg Med 2011 Apr 13;6(2):149-56. Epub 2011 Feb 13.

Department of Emergency Medicine, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168, Rome, Italy.

Atrial Fibrillation management is still a matter for debate. Past research has largely been based on the outpatient setting in which patients are followed during ambulatory visits. Very little data exist on the optimal management of AF in the Emergency Department (ED). This study investigated which factors drive different AF treatments in the ED, describing their use in different hospitals. Finally, the efficacy of different strategies in terms of cardioversion in the ED was analyzed. Charts of patients treated for atrial fibrillation (AF) were collected in 6 EDs in a large metropolitan area over a 24-consecutive month period and were reviewed and analysed. Demographics, comorbidities, treatment strategy and ED outcome were collected. Inclusion criteria were symptom onset <3 weeks and stable hemodynamic conditions at presentation. A propensity score was used to adjust for baseline clinical characteristics and to compare the efficacy of different treatments. 3,085 patients were included in the analysis. Variables associated with a rhythm control strategy were onset of symptoms <48 h, age, dyspnea, palpitations, renal failure and the presence of a mechanical valve. Different EDs applied different strategies in terms of drugs used and the electrocardioversion rate, showing heterogeneity in AF management. Adjusting for the propensity score, electrocardioversion and antidysrhythmic drugs of class Ic were more effective than a wait-and-watch strategy in the ED. Despite international guidelines being respected, AF management is heterogeneous in different ED settings. A rhythm control strategy with electrocardioversion and Class Ic drugs is more effective than a wait-and watch approach during the ED visit. Further research, toward an evidence-based approach to the emergent management of AF in the ED, is still needed.
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http://dx.doi.org/10.1007/s11739-011-0537-3DOI Listing
April 2011

Investigating feedforward neural regulation of circulation from analysis of spontaneous arterial pressure and heart rate fluctuations in conscious rats.

Am J Physiol Heart Circ Physiol 2009 Jan 14;296(1):H202-10. Epub 2008 Nov 14.

Dip. Medicina Interna, Univ. di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

It has been suggested in anesthetized animals that the occurrence of sequences of consecutive beats characterized by systolic arterial pressure (SAP) and RR or pulse interval (PI) changing in the opposite direction (SAP(+)/RR(-) and SAP(-)/RR(+), nonbaroreflex sequences) might represent the expression of neural cardiovascular regulatory mechanisms operating with feedforward characteristics. The aim of the present study was to study nonbaroreflex sequences in a more physiological experimental model, i.e., in conscious freely moving rats. We studied conscious rats before and after 1) complete autonomic blockade (n = 12), 2) sympathetic blockade (n = 10), 3) alpha (n = 7)- and beta (n = 8)-adrenergic blockade, and 4) parasympathetic blockade (n = 10). Nonbaroreflex sequences were defined as three or more beats in which SAP and PI of the following beat changed in the opposite direction. Complete autonomic blockade reduced the number of nonbaroreflex sequences (95.6 +/- 9.0 vs. 45.2 +/- 4.1, P < 0.001), as did sympathetic blockade (80.9 +/- 12.6 vs. 30.9 +/- 6.1, P < 0.001). The selective alpha-receptor blockade did not induce significant changes (80.9 +/- 12.5 in baseline vs. 79.0 +/- 14.7 after prazosin), whereas beta-receptor blockade significantly reduced nonbaroreflex sequence occurrence (80.9 +/- 12.5 in baseline vs. 48.9 +/- 15.3 after propranolol). Parasympathetic blockade produced a significant increase of nonbaroreflex sequences (95.1 +/- 6.9 vs. 136.0 +/- 12.4, P < 0.01). These results demonstrate the physiological role of the nonbaroreflex sequences as an expression of a feedforward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the neural control of the sinus node.
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http://dx.doi.org/10.1152/ajpheart.00358.2008DOI Listing
January 2009

Revisiting the potential of time-domain indexes in short-term HRV analysis.

Biomed Tech (Berl) 2006 Oct;51(4):190-3

Institute of Clinical Physiology, National Research Council, Pisa, Italy.

In the context of HRV analysis, we evaluated the information content of two measures that can easily be derived from the classical RR time-domain indexes. The two measures are: 1) the ratio sd/rmssd, where sd is the RR standard deviation and rmssd is the root mean square of squared differences of consecutive RR beats; and 2) the ratio sd2/sd1, where sd2 and sd1 are extracted from the Poincaré plot and represent the transversal and longitudinal dispersion of the cloud of points (RR(i),RR(i)(+1)). We compared the performance of the two measures with that of the classical LF/HF ratio in a group of healthy subjects who underwent a 70 degrees upright tilt test. The goodness of the results obtained by the two measures, the simplicity of their calculation and their applicability free from a priori assumptions on the characteristics of the data are proposed to the attention of the community involved in the HRV analysis as a possible alternative to the LF/HF ratio.
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http://dx.doi.org/10.1515/BMT.2006.034DOI Listing
October 2006

Effects of residential exercise training on heart rate recovery in coronary artery patients.

Am J Physiol Heart Circ Physiol 2007 Jan 15;292(1):H510-5. Epub 2006 Sep 15.

Dipartimento Medicina Interna, Università di Roma "Tor Vergata," Via Montpellier 1, 00133 Roma, Italy.

The aims of the present study are twofold: 1) to investigate whether heart rate recovery (HRR) after a cycle ergometry test is affected by exercise training and 2) to test the ability of HRR to replicate the baroreflex sensitivity (BRS) changes that occur in response to an exercise training program in coronary artery patients. We randomized 82 coronary artery patients undergoing a residential cardiac rehabilitation program to an exercise training group (TR; n = 43) and an untrained group (UTR; n = 39). All of the patients underwent an exercise test before and after the rehabilitation program. HRR was recorded at the end of the 1st and 2nd min after exercise. BRS was determined at rest before and after treatment. HRR after the 2nd min was significantly improved in TR patients (-21.4 +/- 0.9 beats/min) compared with UTR patients (-17.8 +/- 1.2 beats/min) at the end of the training program. Improvement in HRR paralleled that in BRS in TR patients (from 3.2 +/- 0.3 to 5.3 +/- 0.8 ms/mmHg; P < 0.001), whereas no significant change was evident in UTR patients (from 3.5 +/- 0 to 4.0 +/- 0.4 ms/mmHg; P = 0.230). Our data show that HRR in the 2nd min after the cessation of a cycle ergometer exercise test increased in coronary artery patients after an exercise training period. This result confirms the positive effect induced by exercise training on HRR and extends the conclusions of previous studies to different modalities of exercise (i.e., cycle ergometer). HRR might provide an additional simple marker of the effectiveness of physical training programs in cardiac patients.
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http://dx.doi.org/10.1152/ajpheart.00748.2006DOI Listing
January 2007

Muscle metaboreflex contribution to cardiovascular regulation during dynamic exercise in microgravity: insights from mission STS-107 of the space shuttle Columbia.

J Physiol 2006 May;572(Pt 3):829-38

Dipartimento di Medicina Interna, Università di Roma 'Tor Vergata', Roma, Italy.

One of the most important features of prolonged weightlessness is a progressive impairment of muscular function with a consequent decrease in exercise capacity. We tested the hypothesis that the impairment in musculo-skeletal function that occurs in microgravity results in a potentiation of the muscle metaboreflex mechanism and also affects baroreflex modulation of heart rate (HR) during exercise. Four astronauts participating in the 16 day Columbia shuttle mission (STS-107) were studied 72-71 days before launch and on days 12-13 in-flight. The protocol consisted of 6 min bicycle exercise at 50% of individual V(o2,max) followed by 4 min of postexercise leg circulatory occlusion (PECO). At rest, systolic (S) and diastolic (D) blood pressure (BP), R-R interval and baroreflex sensitivity (BRS) did not differ significantly between pre- and in-flight measurements. Both pre- and in-flight, SBP increased and R-R interval and BRS decreased during exercise, whereas DBP did not change. During PECO preflight, SBP and DBP were higher than at rest, whereas R-R interval and BRS recovered to resting levels. During PECO in-flight, SBP and DBP were significantly higher whereas R-R interval and BRS remained significantly lower than at rest. The part of the SBP response (delta) that was maintained by PECO was significantly greater during spaceflight than before (34.5 +/- 8.8 versus 13.8 +/- 11.9 mmHg, P = 0.03). The tachycardic response to PECO was also significantly greater during spaceflight than preflight (-141.5 +/- 25.2 versus - 90.5 +/- 33.3 ms, P = 0.02). This study suggests that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.
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http://dx.doi.org/10.1113/jphysiol.2005.102426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779995PMC
May 2006

Altered autonomic cardiac regulation in individuals with Down syndrome.

Am J Physiol Heart Circ Physiol 2005 Dec 15;289(6):H2387-91. Epub 2005 Jul 15.

Dipartimento Medicina Interna, Università di Roma Tor Vergata, Via O. Raimondo, 8, 00173 ROME, Italy.

We tested the hypothesis that individuals with Down syndrome, but without congenital heart disease, exhibit altered autonomic cardiac regulation. Ten subjects with Down syndrome (DS) and ten gender-and age-matched healthy control subjects were studied at rest and during active orthostatism, which induces reciprocal changes in sympathetic and parasympathetic traffic to the heart. Autoregressive power spectral analysis was used to investigate R-R interval variability. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. No significant differences between DS and control subjects were observed in arterial blood pressure at rest or in response to standing. Also, R-R interval did not differ at rest. R-R interval decreased significantly less during standing in DS vs. control subjects. Low-frequency (LFNU) and high-frequency (HFNU) (both expressed in normalized units) components of R-R interval variability did not differ between DS and control subjects at rest. During standing, significant increase in LFNU and decrease in HFNU were observed in control subjects but not in DS subjects. Baroreflex sensitivity (BRS) did not differ between DS and control subjects at rest and underwent significant decrease on going from supine to upright in both groups. However, BRS was greater in DS vs. control subjects during standing. These data indicate that subjects with DS exhibit reduced HR response to orthostatic stress associated with blunted sympathetic activation and vagal withdrawal and with a lesser reduction in BRS in response to active orthostatism. These findings suggest overall impairment in autonomic cardiac regulation in DS and may help to explain the chronotropic incompetence typically reported during exercise in subjects with DS without congenital heart disease.
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http://dx.doi.org/10.1152/ajpheart.00560.2005DOI Listing
December 2005

Baroreflex buffering of sympathetic activation during sleep: evidence from autonomic assessment of sleep macroarchitecture and microarchitecture.

Hypertension 2004 Apr 23;43(4):814-9. Epub 2004 Feb 23.

Dipartimento di Medicina Interna-Centro di Riabilitazione Cardiologica San Raffaele Pisana, Università di Roma Tor Vergata, Santa Lucia, Roma, Italy.

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.
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http://dx.doi.org/10.1161/01.HYP.0000121364.74439.6aDOI Listing
April 2004

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

J Hypertens 2003 Aug;21(8):1555-61

Dipartimento di Medicina Interna-Centro di Riabilitazione Cardiologica San Raffaele-Pisana, Université di Roma, Rome, Italy.

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.
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http://dx.doi.org/10.1097/00004872-200308000-00021DOI Listing
August 2003

Conversion from vagal to sympathetic predominance with strenuous training in high-performance world class athletes.

Circulation 2002 Jun;105(23):2719-24

Dipartimento di Medicina Interna-Centro di Riabilitazione Cardiologica S. Raffaele, Università di Roma Tor Vergata, Roma, Italy.

Background: Benefits of moderate endurance training include increases in parasympathetic activity and baroreflex sensitivity (BRS) and a relative decrease in sympathetic tone. However, the effect of very intensive training load on neural cardiovascular regulation is not known. We tested the hypothesis that strenuous endurance training, like in high-performance athletes, would enhance sympathetic activation and reduce vagal inhibition.

Methods And Results: We studied the entire Italian junior national team of rowing (n=7) at increasing training loads up to 75% and 100% of maximum, the latter approximately 20 days before the Rowing World Championship. Autoregressive power spectral analysis was used to investigate RR interval and blood pressure (BP) variabilities. BRS was assessed by the sequences method. Increasing training load up to 75% of maximum was associated with a progressive resting bradycardia and increased indexes of cardiac vagal modulation and BRS. However, at 100% training load these effects were reversed, with increases in resting heart rate, diastolic BP, low-frequency RR interval, and BP variabilities and decreases in high-frequency RR variability and BRS. Three athletes later won medals in the World Championship.

Conclusions: This study indicates that very intensive endurance training shifted the cardiovascular autonomic modulation from a parasympathetic toward a sympathetic predominance. This finding should be interpreted within the context of the substantial role played by the sympathetic nervous system in increasing cardiovascular performance at peak training. Whether the altered BP and autonomic function shown in this study might be in time hazardous to human cardiovascular system remains to be established.
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http://dx.doi.org/10.1161/01.cir.0000018124.01299.aeDOI Listing
June 2002

Hemodynamic and autonomic correlates of postexercise hypotension in patients with mild hypertension.

Am J Physiol Regul Integr Comp Physiol 2002 Apr;282(4):R1037-43

Dipartimento di Medicina Interna, Centro di Riabilitazione Cardiologica San Raffaele and Università di Roma Tor Vergata, 00173 Rome, Italy.

We investigated the interplay of neural and hemodynamic mechanisms in postexercise hypotension (PEH) in hypertension. In 15 middle-aged patients with mild essential hypertension, we evaluated blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), forearm (FVR) and calf vascular resistance (CVR), and autonomic function [by spectral analysis of R-R interval and BP variabilities and spontaneous baroreflex sensitivity (BRS)] before and after maximal exercise. Systolic and diastolic BP, TPR, and CVR were significantly reduced from baseline 60-90 min after exercise. CO, FVR, and HR were unchanged. The low-frequency (LF) component of BP variability increased significantly after exercise, whereas the LF component of R-R interval variability was unchanged. The overall change in BRS was not significant after exercise vs. baseline, although a significant, albeit small, BRS increase occurred in response to hypotensive stimuli. These findings indicate that in hypertensive patients, PEH is mediated mainly by a peripheral vasodilation, which may involve metabolic factors linked to postexercise hyperemia in the active limbs. The vasodilator effect appears to override a concomitant, reflex sympathetic activation selectively directed to the vasculature, possibly aimed to counter excessive BP decreases. The cardiac component of arterial baroreflex is reset during PEH, although the baroreflex mechanisms controlling heart period appear to retain the potential for greater opposition to hypotensive stimuli.
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http://dx.doi.org/10.1152/ajpregu.00603.2001DOI Listing
April 2002