Massimo Zannoni

Effects of nebivolol and atenolol on small arteries and microcirculatory endothelium-dependent dilation in hypertensive patients undergoing isometric stress.

Objective To examine the effects on small arteries and on the cutaneous microcirculatory system of nebivolol and atenolol in hypertensive patients. Design Twenty hypertensive patients were randomly assigned to receive nebivolol or atenolol in a single-blind, placebo-controlled cross-over study. Piezoelectric plethysmography on the third finger, laser Doppler on the third finger at rest and after iontophoretic administration of acetylcholine, and pressure–heart rate monitoring, were carried out both at rest and during handgrip. The tests were performed 45 min after 5 mg nebivolol or 100 mg atenolol administration, then repeated 2 days later with a placebo and, after a further 2 days, with atenolol or nebivolol again. Results Both atenolol and nebivolol reduced diastolic blood pressure values and heart rate, as well the increase of blood pressure and heart rate during handgrip. No change was recorded after placebo. Piezoelectric plethysmography showed a significant increase in the ratio between time to peak and total time (PT/TT), calculated on the sphygmic wave, during handgrip (0.295 ± 0.005 versus 0.231 ± 0.015, P < 0.005). After nebivolol, a decrease was recorded in rest conditions (0.185 ± 0.008 versus 0.231 ± 0.015, P < 0.005) with no statistically significant increase during handgrip, whereas atenolol showed an increase in the PT/TT ratio at rest, with a sustained response during handgrip. Laser Doppler showed an increased response to acetylcholine only after nebivolol. Conclusions Nebivolol and atenolol significantly reduced diastolic blood pressure and heart rate, favourably modulating response to handgrip. Nebivolol improved small artery distensibility index. Endothelium-dependent cutaneous vasodilation after acetylcholine demonstrated a lack of response with atenolol whereas nebivolol favourably acts on endothelial function.

Effect of Glutathione Infusion on Leg Arterial Circulation, Cutaneous Microcirculation, and Pain-Free Walking Distance in Patients With Peripheral Obstructive Arterial Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease. PATIENTS AND METHODS Forty patients with Fontaine stage II peripheral artery disease who were seen between September 2000 and March 2001 at the vascular laboratory and ward of the Division of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind, placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment with intravenous glutathione twice a day or saline solution twice a day for 5 days. Treatments were administered in a double-blind manner. The 2 groups of patients underwent measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements and tests were repeated 12 hours after the last infusion. RESULTS Between the 2 groups, hemodynamic tests showed no differences in baseline values and at rest after treatment. At rest, no differences were observed between basal and posttreatment values; findings in the saline group were similar during tests before and after the infusion period. In the glutathione group, we observed increases in PFWD (196+/-15 vs 143+/-11 m; P<.04), macrocirculatory flow after treadmill test with plethysmography at the end of treatment (9.3+/-2 vs 2.8+/-0.5 mL per 100 mL/min; P<.002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion units (PU), at the end of infusions (14.4+/-3.2 vs 6.18+/-1.5 PU; P<.005), with a greater area under the curve after treatment (705+/-103 vs 508+/-45 PU/s; P<.001) and reduced time to flow motion (32+/-4 vs 48+/-11 seconds; P<.05). CONCLUSION In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters.

Comparative Efficacy of Ketanserin and Pentoxiphylline in Treatment of Raynaud's Phenomenon

In a randomized, placebo-controlled, crossover study, 15 ambulatory pa tients with Raynauds phenomenon, treated for three weeks with ketanserin 80 mg/day and pentoxiphylline 1,200 mg/day, were evaluated by subjective symp tom scores, daily frequency and duration of attacks, and photoplethysmog raphy, at room temperature and after cold test. Reduced subjective symptoms and duration of attacks, together with improved cold test plethysmography, were significant only after ketanserin. All subjective symptom scores also im proved after ketanserin but only for cyanosis and paresthesia after pentoxiphyl line. Excellent results were obtained in 4 cases after ketanserin and in 1 case with pentoxiphylline. The authors discuss the greater importance of antivaso spastic action over antiaggregating and hemorheologic effects in Raynauds phenomenon therapy, as well as the pathogenetic role of serotonin.

Increased endogenous nitric oxide production induced by physical exercise in peripheral arterial occlusive disease patients

The effects of 14-day physical exercise or iloprost treatment (0.5-2 ng/Kg/min) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease (Fontaine Stage II). Peripheral venous blood samples and 4-h urine samples were collected before, immediately after 14 days of therapy and 7-10 days after therapy in order to evaluate neutrophil adhesion, nitrite/nitrate and cGMP excretion rates. A longer pain free walking distance was observed after exercise, compared to iloprost (>500 m in 3/10 subjects). Urinary nitrite/nitrate, as well as cGMP concentrations, significantly increased after exercise. Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion. No variations were observed in these parameters in iloprost treated patients. The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise. The results from the present and previous observations indicate that, besides pharmacological treatments, a regular aerobic exercise improves peripheral arterial occlusive disease.

Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

Efficacy of Ketanserin in the Therapy of Raynaud's Phenomenon: Thermometric Data

After a two-week washout (WO) period with placebo 1 capsule/ bid, 12 patients suffering from stable Raynauds phenomenon were treated with ketanserin (K) 40 mg/ bid for fifteen days. Blood pressure, heart rate, and laboratory parameters were evaluated at the end of each period. Patients used diary cards to record the number, duration, and intensity of attacks. Computerized thermometry of the fingers was evaluated at basal temperature after acclimatization, 23°C for thirty minutes; after cold test, 10°C for five minutes; and after thermal recovery, 23°C for eighteen minutes. Results were analyzed statistically by use of Students t-test for paired data (p<0.05). No marked changes were observed in the symptoms of the attacks, but K proved effective in significantly reducing the number and duration of daily attacks and in promoting their spontaneous regression. Thermometry revealed a parallel increase in temperatures, particularly basal and recovery values. The data suggest increased flow and decreased vasospasm following 5-HT2 receptor blockade.

Tryptase serum level as a possible indicator of scombroid syndrome.

Introduction. Scombroid syndrome (histamine fish poisoning – HFP) is a complex of symptoms caused by biogenic amines, mainly histamine, contained in seafood. The diagnosis of HFP is quite difficult as the symptoms of this particular condition are similar to the symptoms of a normal allergic syndrome. Materials and methods. We have collected 10 cases (3 male and 7 female) of HFP and 50 non-HFP patients (35 female and 15 male) with allergic disorders, all from the Emergency Department of Ospedale Civile Maggiore in Verona. Results. As expected, tryptase serum concentrations of most of the patients with allergic or anaphylactic disorders were increased above normal value (24.4 ± 8.0 ng/mL mean ± SD, normal value <11 ng/mL), whereas the tryptase serum concentrations of all the 10 patients with HFP were within the normal range (8.1 ± 1.8 ng/mL). Discussion. Our data suggest that tryptase serum concentrations can discriminate between the allergic and HFP syndromes. As the tryptase half-life is 90–120 min, blood samples must be taken 1–2 h from the beginning of symptoms. Conclusions. Finding a biomarker could help physicians to formulate a correct diagnosis and thus in choosing the best therapeutic strategy. In this work, we analyzed the role of tryptase serum concentrations to differentiate real allergic syndromes from the HFP syndrome, which causes similar histamine-mediated effects by a different mechanism.

Effects of long-term nicardipine treatment on hemodynamics of large arteries in essential hypertension

SummaryThe effects of the calcium-entry blocker nicardipine on brachial hemodynamics were studied in 22 patients (18 male, 4 female) with essential hypertension, who were treated with 20 mg tid for 1 year. Compliance, characteristic impedance, vascular resistances, and tangential tension were measured before treatment and after 1, 3, and 12 months of treatment by an automatic recording from a B-mode, high-resolution, real-time scanner and pulsed Doppler velocimetry for the calculation of the flow volume. We observed statistically significant variations in compliance and impedance after 1 month (3.21±0.59 dyn−1 cm4 10−7 vs. 1.26±0.16 dyn−1 cm4 10−7 and 50.6±4.7 dyn s cm−5102 vs. 91.4 ±7.3 dyn s cm−5 102, respectively; mean±SEM; p<0.001), while tangential tension was significantly reduced after only 3 months (23.2±2.2 mmHg vs. 25.4±2.3 mmHg cm; p<0.05). The correlation between variations in mean blood pressure and in the hemodynamic parameters studied remained statistically significant throughout the study. Nicardipine improved the parameters of large-artery hemodynamics that favor a normal systolic pulse.

Red Blood Cell Distribution Width Is an Independent Predictor of Outcome in Patients Undergoing Thrombolysis for Ischemic Stroke

&NA; An appropriate and timely management, including early diagnosis and accurate prognostication, is the mainstay for managed care of patients with acute ischemic stroke. Since red blood cell distribution width (RDW) was found to be an independent predictor of clinical outcomes in patients with thrombotic disorders, we designed a retrospective observational study to investigate whether the RDW value may also retain predictive significance in stoke patients undergoing thrombolytic therapy. This retrospective study was based on all patients admitted to the Emergency Department (ED) of the University Hospital of Verona (Italy) with a diagnosis of ischemic stroke, who underwent systemic thrombolysis between January 2013 and June 2015. The RDW value along with basal clinical characteristics was recorded at ED admission. The final study population consisted of 316 patients. A significant association was found between stroke severity (NIHSS score) and RDW (r = 0.322; p < 0.001). The median RDW value in patients with clinical improvement after thrombolysis was significantly lower than in patients without (13.4 vs. 14.1%; p < 0.001). The diagnostic accuracy (area under the curve) of RDW for predicting the lack of neurological improvement was 0.667. In univariate analysis, RDW >14.5% was associated with increased rate of no neurological improvement (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.37‐4.13), an association remaining significant also in multivariate analysis (OR, 1.85; 95% CI, 1.13‐3.32). Survivor curve analysis showed that patients with RDW values ≥14.5% had a higher risk of 1‐year mortality and shorter survival. These results suggest that RDW assessment at ED admission may provide valuable diagnostic and prognostic information in patients with acute ischemic stroke.

Activity of cardiopulmonary baroreceptors, peripheral resistance and cutaneous microcirculation in patients with peripheral obstructive arterial disease.

Abstract. Arosio E, De Marchi S, Prior M, Zannoni M, Lucchese L, Lechi A (Division of Vascular Medicine and Rehabilitation, University of Verona, Italy). Activity of cardiopulmonary baroreceptors, peripheral resistance and cutaneous microcirculation in patients with peripheral obstructive arterial disease. J Intern Med 2000; 247: 471–478.