Remo Melchio

Plasma endothelin levels in cirrhotic subjects

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.

Blood pressure and heart rate in young thalassemia major patients

The analysis of blood pressure (BP) and heart rate (HR) variability is currently used to investigate the mechanisms responsible for cardiovascular control; therefore, we assessed whether an impairment of 24-h BP and HR profiles and sympathovagal interaction modulating cardiovascular function was present in patients with thalassemia major (TM) in preclinical phase of heart disease. Nine beta-thalassemic patients 18 years old without clinical signs of cardiac failure and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series with four harmonics was used to describe the diurnal blood pressure profile. Mean 24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were significantly lower in TM patients than in normal subjects (P < .05). A significantly higher nighttime HR value was found in TM patients (P < .05). More than 40% of the TM patients did not show a significant diurnal BP and HR rhythm. In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was significantly lower than in controls (P < .01). The night/day differences of systolic BP, diastolic BP, and HR were significantly lower in TM patients than in normals (P < .01). Furthermore, we performed power spectral analysis on short-term continuous finger BP and HR data in supine position and during passive head-up tilt. Total spectral power of systolic BP was significantly lower in patients than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM patients compared to controls (P < .05). High-frequency power of HR was significantly higher in patients than controls (P < .05). The baroreflex gain assessed by alpha-index was the same in supine position but was higher in TM patients during passive tilt (P < .05). An inverse relationship between LF/HF ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma norepinephrine levels were significantly lower in thalassemics (P < .005). In young TM patients in a preclinical stage of heart disease, these findings demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term variability of BP and HR, in particular in the LF range, showing a diminished sympathetic activity.

Twenty-Four-Hour Power Spectral Analysis by Maximum Entropy Method of Blood Pressure in Primary Hyperaldosteronism

In the present study we estimated the periodic profiles and variance structure of systolic blood pressure, diastolic blood pressure, heart rate and mean arterial pressure by using an autoregressive model of power spectrum, Maximum Entropy Method (MEM) in 8 patients with primary aldosteronism, during long-term therapy with nicardipine slow release. The four blood pressure variables were measured at 30-min intervals, using a noninvasive device (Spacelabs 90202) in 8 hypertensive patients of whom 6 with idiopathic aldosteronism (IHA) and 2 with dexamethasone-suppressible aldosteronism (DSH), before and after 24 weeks of 80 mg nicardipine daily. Blood pressure data were processed by MEM and spectral profiles were obtained. During nicardipine therapy all patients showed a significant decrease of 24-h ambulatory blood pressure values (p < 0.01). Before therapy, spectrum analysis by MEM indicated the presence of high frequency distribution of peaks for SBP, DBP, MAP and HR. The MEM power spectrum showed an increase in amplitude of sharp peaks of systolic, diastolic, MAP and heart rate in all patients after therapy at 24 h corresponding to the circadian rhythm blood pressure. Furthermore, the trend of these variables synchronized themselves in the same period after 24 weeks of nicardipine therapy, with spectral patterns of blood pressure similar to those of normotensive subjects. This chronobiologic approach, by Maximum Entropy Method, may be used as an alternative statistical analysis to search for possible rhythmic behavior of ambulatory blood pressure data before and after pharmacological treatment in secondary hypertensive patients.

Spectral characteristics of heart rate and blood pressure variability in primary aldosteronism

A disturbance of the autonomic cardiovascular function has been postulated in primary aldosteronism as a possible mechanism for hypertension. Using the method of spectral analysis of heart rate and blood pressure variability, the aim of this study was to assess sympathovagal interactions modulating cardiovascular function and baroreflex control in patients with primary aldosteronism. Seventeen patients (7 with adenomas and 10 with idiopathic hyperaldosteronism) and a control group of 11 essential hypertensives (EH) and 10 normotensive subjects were studied. Continuous finger blood pressure was measured using a Finapres device and heart rate was measured using an electrocardiographic monitor. The studies were conducted in each patient for 20 min in the supine position and 10 min during a passive head-up tilt to 60 degrees. The low frequency and the low frequency-to-high frequency ratio of systolic and diastolic blood pressures were significantly higher both in primary aldosteronism and in EH patients compared with normotensives (P < .01). Impaired response to tilt was found in the heart rate and blood pressure variability in primary aldosteronism and EH patients; the increase in low frequency was smaller than in normotensives. Baroreflex gain (assessed by alpha index) was less in primary aldosteronism and EH patients as compared with normotensives. These findings may suggest that volume expansion or sympathetically mediated central translocation of the blood volume, or both, could stimulate the cardiopulmonary receptors and impair the baroreflex gain. Our findings suggest that an enhanced peripheral vascular responsiveness to a normal sympathetic outflow may be involved in the pathogenesis of hypertension in primary aldosteronism.

Hormonal Aspects of the Relation of Liver Cirrhosis to Essential Hypertension

The association of liver cirrhosis with arterial essential hypertension has been previously described. The present study extends the previous reports by investigating the hormonal relationships that may occur in patients with established essential hypertension associated to liver cirrhosis. We studied the renin-angiotensin, the adrenergic systems and other vasoactive hormones such as arginine-vasopressin, atrial natriuretic peptide, endothelin and parathyroid hormone in cirrhotic patients with and without essential hypertension. The data suggested that the coincidence of arterial hypertension in cirrhotic patients was characterized by the following findings: a decreased renin-angiotensin activity; a reduced systemic vasodilatation; an increased peripheral pressor effect of vasoactive hormones and an increased effective blood volume.

Incidence and diagnosis of pulmonary embolism in Northern Italy: a population-based study.

Pulmonary embolism (PE) is a common disorder with a high mortality rate. To date, most of the data on the incidence of PE originate from studies performed either in United States [1]. On the other hand, only few studies have provided data on its incidence in Europe [2] and in particular, to our knowledge, no data have been published on the Italian population. Computed tomographic pulmonary angiography (CTPA) is generally considered the diagnostic test of choice in patients with suspected PE and ventilation perfusion (V/Q) lung scan is recommended only when CTPA is not available or contraindicated [3]. Concerns of high radiation exposure have been raised as an issue for CTPA in particular in youngwomen inwhom the relative lifetime risk of breast or lung cancer is estimated to increase by 1.7 to 5.5% [4]. Thus, some experts have recommended V/Q scan as the initial imaging test in premenopausal women [5,6]. However, whether different diagnostic strategies based on age and gender are applied in clinical practice remains poorly demonstrated. Aims of this study are therefore to provide an estimate of the incidence of PE in a well-defined geographic area in the Northern part of Italy using data recorded in the Piemonte Region hospital database and to evaluate the current diagnostic approach with non-invasive imaging tests according to age and gender. According to the National Institute of Statistics (ISTAT), the Piemonte Region in Northern Italy has a population of about 4,500,000 people (2008: 4,432.571; 2009: 4,446,230; 2010: 4,457,335) and the hospital database contains data on 764,052 hospital admissions from 2009 to 2011 (2009: 257,418; 2010: 255,223; 2011: 251,411). All patients hospitalized with an objective diagnosis of acute PE between January 2009 and December 2011 were identified using the following ICD-9-CM codes: 415.11 (Iatrogenic PE and infarction), 415.19 (Other PE), 639.6 (PE complicating abortion, ectopic or molar pregnancies), and 673.0–673.8 (PE complicating pregnancy, childbirth or the puerperium). In this group, we identified patients with a procedural code of CTPA (87.41), lung scan (92.15) and pulmonary angiography (88.43). For each patient, the following characteristics were collected: age, gender, PE diagnostic procedure, duration of hospital stay, and in hospital mortality. Age and sex related differences in the use of CTPA and lung scan were determined. Data were expressed as absolute numbers, percentage, and mean±standard deviation (SD) or median and range. The percentage of hospital admissions for PE on the total number of admissions during the same period was calculated. Annual

Statistical evaluation of circadian blood pressure rhythm during isradipine long-term therapy.

In this study, using the two-step truncated Fourier series with four harmonics, we analysed the diurnal blood pressure profile in 13 mild-moderate essential hypertensive patients during isradipine long-term therapy. Circadian parameters such as the amplitudes and phases of the four harmonics and the overall amplitude and phase were obtained from the model. The total duration of the study was 26 weeks. Ambulatory blood pressure was measured at 15-min, intervals using a Takeda TM 2420 device after 2 weeks of placebo and after 6 and 26 weeks of isradipine (5 mg daily) respectively. After 6 and 26 weeks therapy the blood pressure values showed a significant decrease, although the daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by isradipine treatment. Both the night/day differences and the overall amplitude/acrophases were statistically significant at 0,6 and 26 weeks. According the nocturnal blood pressure fall, we found that long-term therapy with isradipine increased the number of patients with nocturnal blood pressure fall and reducing the early morning blood pressure rise.In conclusion, the two-step method Fourier analysis represents a novel and useful statistical approach to evaluate the presence of a significant diurnal blood pressure rhythm and to provide the circadian parameters of the 24-h blood pressure profile during pharmacological therapy.

Dopaminergic Regulation of Aldosterone Secretion: Assessment in Different Subtypes of Primary Aldosteronism and in Essential Hypertension

The inhibitory effect of dopamine on aldosterone secretion was investigated in patients with different types of primary aldosteronism, six with idiopathic hyperaldosteronism (IHA) and four with dexamethasone-suppressible hyperaldosteronism (DSH), and in 10 patients with essential hypertension. The effects of 10 mg metoclopramide given intravenously, 10 mg bromocriptine given orally and 100 μg adrenocorticotrophic hormone given intravenously on plasma aldosterone and renin activities were investigated in all patients. Metoclopramide induced a rise in plasma aldosterone activity only in patients with IHA and not in those with DSH and essential hypertension. After bromocriptine plasma aldosterone concentrations decreased in patients with IHA only, and after adrenocorticotrophic hormone plasma aldosterone concentrations increased in patients with DSH only. Plasma renin activity was unaffected in all cases. These results provide evidence of increased endogenous dopaminergic inhibition of aldosterone secretion in IHA and of a blunted aldosterone response in both DSH and essential hypertension.

Short-term prognosis of intracranial haemorrhage in patients on oral anticoagulant or antiplatelet drugs

BACKGROUND Intracranial haemorrhage (ICH) is the most feared complication of oral vitamin K antagonists (VKAs) and antiplatelet drugs. Little data are available on the clinical course of antithrombotic drug-associated ICHICH. The main aim of the VKA- and Antiplatelet Drug-Associated ICH Prognosis (VAIP) study is to investigate predictors of short-term prognosis in ICH patients, and to analyse characteristics and prognosis of patients with antithrombotic drugs-associated ICH. METHODS VAIP is designed as a retrospective cohort study. Consecutive adult patients with an ICH objectively documented by neuroimaging, occurring during treatment with VKAs or ADs, admitted to the Cuneo hospital, Italy, from 2005 to 2010, were included. For a non-exposed group, we randomly selected patients with ICH not on antithrombotic treatment. RESULTS Overall, 451 patients were included. In particular, 75 patients were on VKAs and 96 on antiplatelet drugs. The site of haemorrhage was intracerebral in 274 (60.8%) patients, subdural in 156 (34.6%), and subarachnoid in 21 (4.7%). Mortality rate was 35.8%, 4.5%, and 28.6%, respectively. In the multivariate analysis, independent predictors of in-hospital death were: age >80years (hazard ratio [HR] 2.3, 95% confidence interval 1.5-3.5), Glasgow Coma Scale [GCS]<8 (HR 7.8, 5.0-12.1), treatment with VKAs (HR 2.0, 1.2-3.4) and antiplatelet drugs (HR 1.8, 1.1-3.0). Neurosurgical treatment was an independent predictor of survival (HR 0.5, 0.3-1.0). Among patients with VKA-associated ICH, independent predictors of in-hospital death for ICH were: age >80years (HR 4.4, 1.6-12.0), GCS <8 (HR 12.0, 4.1-34.8), recent onset of symptoms (HR 4.2, 1.6-11.3), and neurosurgical treatment (HR 0.1, 0.0-0.8). CONCLUSION Our results suggest that the main predictors of ICH in-hospital prognosis in a tertiary neurosurgical center are advanced age, GCS at admission, previous treatment with VKAs and antiplatelet drugs, and neurosurgical treatment.

Respiratory failure in portal hypertension: at the heart of the matter

A 60-year-old man presented to our hospital because of worsening dyspnea and chronic fatigue. He had a history of cryptogenic liver fibrosis diagnosed 8 years prior, during an hospital admission for esophageal variceal bleeding: at that time extensive analysis (including liver biopsy) was obtained and a transjugular intrahepatic portosystemic shunt (TIPS) was finally performed because endoscopic and medical therapy failed to stop the variceal bleeding. Post-discharge, the patient was lost to follow-up, and he had discontinued all medications. On physical examination, he was alert, dyspneic at rest and cyanotic with evident digital clubbing. His vital signs were: blood pressure 110/60 mmHg, pulse rate 88 beats per minute, respiration rate 18 breathes per minute, arterial oxygen saturation with pulse oximetry breathing room air 81 %, breathing oxygen in reservoir 93 %. Platypnea and orthodeoxia were observed. Lung auscultation revealed basalar light crackles bilaterally. The abdomen was soft, and nontender, without distention or ascites. At routine laboratory analysis haemoglobin was 23 g/dL, hematocrit 64.4 %, platelets 34,000/lL, prothrombin activity 44 % and aPTT 47 s, serum bilirubin 2.8 mg/dL, serum creatinine 2.1 mg/dL. Arterial blood gas analysis breathing room air revealed a pH of 7.49, pCO2 of 23 mmHg, PaO2 of 45 mmHg, and bicarbonate of 21 mEq/L. Calculated alveolar–arterial oxygen gradient was 76 mmHg. Arterial blood gas analysis breathing oxygen in reservoir showed a pH of 7.49, pCO2 of 24 mmHg, PaO2 of 71 mmHg, and bicarbonate of 22 mEq/L. A chest X-ray study showed increased vascular marking at both lung bases and a 12-lead electrocardiogram revealed a normal sinus rhythm. A bedside cardiac echoscopy showed normal right and left ventricular size and function without significant pulmonary hypertension. An abdominal ultrasound showed hepatic steatosis and hypertrophic caudate lobe, without peritoneal effusion. The presence of severe respiratory failure without pleural and parenchymal disease or pulmonary hypertension in the context of portal hypertension was consistent with hepatopulmonary syndrome (HPS); therefore, contrast-enhanced transthoracic echocardiography with saline was performed, and the diagnosis of an intrapulmonary shunt was confirmed by showing microbubble opacification of the left heart chambers five cycles after right atrial passage. The bubbles appeared to enter the left atrium from the pulmonary veins, and no interatrial shunting was detected (Fig. 1, Video in Supplementary File). Hepatopulmonary syndrome is a serious vascular complication of portal hypertension, characterized by pulmonary vascular dilatation with intrapulmonary shunts leading to various degrees of arterial hypoxemia and increased Electronic supplementary material The online version of this article (doi:10.1007/s11739-016-1413-y) contains supplementary material, which is available to authorized users.