Two-dimensional, M-mode and Doppler-derived echocardiographic parameters in sedated healthy growing female sheep.

Despite the fact that sheep are a widely used animal model in cardiovascular research, reference values for transthoracic echocardiography in normal growing animals are not available. Eight healthy female lambs underwent two-dimensional, M-mode and pulsed wave Doppler echocardiographic examination at 100 days of age and every three months thereafter over a 12-month period. The study was conducted under sedation with midazolam, butorphanol and constant rate infusion of intravenous propofol. Their growth phase was completed at about one year of age. All the echocardiographic parameters considered were significantly correlated with body weight and age class except for the left ventricular systolic and diastolic diameters. Functional indices were not correlated to body weight or age except for the E-point to septal separation distance (EPSS). Doppler-derived parameters were not influenced by independent variables. Transthoracic echocardiography can be considered an applicable method for cardiovascular research using a growing lamb animal model after appropriate adjustments for age and body size.

Blood pressure control has distinct effects on executive function, attention, memory and markers of cerebrovascular damage.

Hypertension causes cognitive impairment, involving mainly executive functions, but the effect of blood pressure (BP) control on the different cognitive domains is still debated. We correlated executive function, attention and memory with BP control and cerebrovascular damage in 60 undemented middle-aged hypertensives at baseline and after 6-year follow-up. At first evaluation, the patients with poor BP control had higher score of white matter lesions, reduced cerebrovascular reserve capacity and greater carotid intima-media thickness (IMT) than those with good BP control. Performance on executive tests correlated with IMT and with performance on attention tests, which was impaired by low diastolic BP. At long-term follow-up, performance in attention and executive tests improved in spite of the minor improvement of BP control, increased IMT and worse memory. Low diastolic BP has a negative effect on attention, which affects executive performance at first cross-sectional examination. This confounding effect has to be taken into consideration when planning studies on cognitive function. Longitudinal studies are required to unravel the effect of BP control on cognitive function, as only long-term antihypertensive treatment improves both attention and executive performance.

High angiotensin II state without cardiac remodeling (Bartter's and Gitelman's syndromes): are angiotensin II type 2 receptors involved?

BACKGROUND/AIMS: While Angiotensin II (Ang II) is a major factor in the development of cardiomyocyte hypertrophy and a pivotal role for Ang II signals via ERK1/2 has been identified, mechanism(s) responsible are still unclear. As Bartter's and Gitelman's syndrome patients (BS/GS) have increased Ang II, and yet normo/hypotension, hyporesponsiveness to pressors and blunted Ang II signaling via type 1 receptors (AT1R), this study assesses BS/GS's left ventricular (LV) mass and structure as well as Ang II induced ERK1/2 phosphorylation compared with essential hypertensive patients (EH) and normotensive healthy subjects (C) to gain insight into Ang II mediated processes. METHODS: Indices of cardiac hypertrophy were determined by M-mode, two-dimensional echo Doppler and ERK phosphorylation by Western blot. RESULTS: None of BS/GS exhibited LV remodelling; LV mass, LV end-diastolic volume and mass/volume ratio were unchanged vs C (60+/-14 g/m2 vs 64+/-12, 64+/-12 ml/m2 vs 60+/-8 and 0.95+/-0.2 vs 1.0+/-0.2, respectively) and reduced vs EH (119+/-15, p<0.001, 78+/-9, p<0.05 and 1.52+/-0.15, p<0.01). Despite BS/GS's higher plasma renin activity and aldosterone and unchanged level of AT1R, Ang II induced ERK1/2 phosphorylation was reduced vs both C and EH: 0.64 d.u.+/-0.08 vs 0.90+/-0.06 in C, p<0.006, and vs 1.45+/-0.07 in EH, p<0.001. CONCLUSION: The data point to a direct cardioremodeling role for Ang II and support a role of Ang II type 2 receptor (AT2R) signaling as involved in the lack of cardiovascular remodeling in BS/GS. However, further studies using more direct approaches to demonstrate the effects of AT2R signaling must be pursued.

Fibrinogen kinetics and protein turnover in hypertension: Effects of insulin.

BACKGROUND AND AIM: Hyperfibrinogenemia, a cardiovascular risk factor, is frequent in hypertension and largely unexplained. In this study, we measured fibrinogen production and whole-body protein turnover under both basal and hyperinsulinemic states, in hypertensive [H] and control [C] subjects, using a leucine stable isotope tracer and precursor-product relationships. METHODS AND RESULTS: Since hypertension is often a feature of the "metabolic", insulin resistance syndrome, which in turn affects both fibrinogen kinetics and whole-body protein turnover, we selected hypertensive subjects without the metabolic syndrome. Following basal measurements, an euglycemic, approximately euaminoacidemic, hyperinsulinemic clamp was performed, with plasma insulin raised to 700-900 pmol/L. In H, rates of the fractional and absolute synthesis (FSR and ASR, respectively) of fibrinogen were 30%-40% greater (p<0.05 or less) than in C in both states, whereas leucine turnover was normal. Hyperinsulinemia did not modify fibrinogen synthesis in either group with respect to baseline, whereas it suppressed leucine appearance from endogenous proteolysis by approximately 40% to same extent in both groups. Amino acid clearance was similar in both the H and C subjects. In H, the insulin-mediated glucose disposal (M) was approximately 25% lower, (although insignificantly) than in controls, showing no overall insulin resistance. There was an inverse correlation between M and fibrinogen FSR during the clamp. CONCLUSIONS: In essential hypertension fibrinogen production is increased, is not further stimulated by insulin, and is inversely related to insulin sensitivity at high-physiological insulin concentrations. Amino acid disposal and basal as well as insulin-responsive protein degradation rates are instead normal.

Intravenous thrombolysis in the emergency department for the treatment of acute ischaemic stroke.

BACKGROUND AND AIMS: Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rt-PA) improves outcome in patients with ischaemic stroke treated within 3 h of symptom onset, but its extended implementation is limited. A pilot study was designed to verify whether evaluation of patients with acute ischaemic stroke and their treatment with intravenous rt-PA in the emergency department (ED), followed by transportation to a semi-intensive stroke care unit, offers a safe and effective organisational solution to provide intravenous thrombolysis to acute stroke patients when a stroke unit (SU) is not available. METHODS: After checking for inclusion and exclusion criteria, ED doctors contacted the stroke team with a single page, located family members and urgently obtained computed tomography scan and laboratory tests. A stroke team investigator clinically assessed the patient, obtained written informed consent and supervised intravenous rt-PA in the ED. After treatment, the patient was transferred to the SU for rehabilitation and treatment of complications, under supervision of the same stroke team investigator. RESULTS: 52 patients were treated with intravenous rt-PA within 3 h of symptom onset. 20 patients (38%) improved neurologically after 24 h, the number increased to 30 (58%) after one week. At 3 months 22 patients had a favourable outcome (43%). The 3-month mortality rate was 12%. Symptomatic cerebral haemorrhage was observed in two patients (4%). CONCLUSIONS: Intravenous rt-PA administration in the ED is an effective organisational solution for acute ischaemic stroke when an SU is not established.

Effect of doxazosin on oxidative stress related proteins in essential hypertensive patients.

The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22(phox) and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22(phox) and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22(phox) and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.

Comparison between nifedipine and carvedilol in the treatment of de novo arterial hypertension after liver transplantation: preliminary results of a controlled clinical trial.

There is no controlled clinical trial on the treatment of de novo arterial hypertension after liver transplantation (LT) a common complication using calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study was to compare the efficacy and safety of nifedipine, a calcium channel blocker, and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who developed arterial hypertension after LT. The data on the first 30 patients who have completed 12-month follow-up are reported herein. Eighteen patients received nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly at the outpatient clinic for 1 year. If patients developed severe adverse effects to nifedipine, they were switched to carvedilol and vice versa (therapy failure). The two groups were similar for clinical features, indications for LT, immunosuppressive therapy, and baseline blood pressures. A failure of treatment was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12 patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of 18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of the nine nonresponders to nifedipine responded to carvedilol. The efficacy of monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol monotherapy is as effective as nifedipine but far better tolerated.