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Biomedical subjects

G Gensini

Publications and source records attributed to G Gensini.

At least 19 recordsLinked to original sources
PubMed2000

Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes.

OBJECTIVE: Cardiac hypertrophy due to pressure overload is associated with several cellular electrophysiological alterations such as prolongation of action potential duration (APD), decrease in transient outward current (Ito) and occurrence of the pacemaker current I(f). These alterations may play a role in sudden arrhythmic death, which is a major risk factor in myocardial hypertrophy and failure. Since angiotensin II is a key signal for myocyte hypertrophy, we tested if an 8-week treatment of old spontaneously hypertensive rats (SHR) with the antagonist of type-1 angiotensin II receptor (AT1), losartan (10 mg/kg/day), was able to influence the cellular electrophysiologic remodeling associated with cardiac hypertrophy. METHODS: Left ventricular myocytes were isolated from control (CTR) or losartan-treated (LOS) 18-month old SHR. Patch-clamped LVM were superfused with a normal Tyrode's solution (to measure action potential) or appropriately modified Tyrode's solution (to measure Ito and I(f)). RESULTS: Heart weight to body weight ratio (HW/BW) was significantly smaller in LOS (5.69 +/- 0.25 mg/g) than in CTR rats (6.67 +/- 0.37 mg/g; P < 0.05). Membrane capacitance, an index of cell size, was significantly reduced in LOS (342 +/- 12, n = 92) vs. CTR (422 +/- 14 pF, n = 96, P < 0.001). APD was significantly shorter in LOS than in CTR (at -60 mV: 197 +/- 23 vs. 277 +/- 19 ms, n = 28, P < 0.001); this effect was paralleled by a larger maximum Ito density in the LOS group (LOS: 15.1 +/- 1.4 pA/pF, CTR: 10.0 +/- 0.8 pA/pF) (n = 27, P < 0.02). I(f), elicited by hyperpolarizing steps (range: -60 to -130 mV), was consistently recorded in SHR cells; however, its maximal specific conductance was significantly lower in LOS than in CTR rats (28.6 +/- 3.6 vs. 54.2 +/- 8.0 pS/pF, n = 55, P < 0.001). Voltage of half-maximal activation (V1/2) of both Ito and I(f) was unchanged by the treatment. CONCLUSIONS: AT1 receptor blockade with losartan prevents the development of myocyte hypertrophy and associated electrophysiological alterations in old SHR.

Action Potentials↗
PubMed2000

Automated classification of human atrial fibrillation from intraatrial electrograms.

The assessment of the degree of organization and the classification of atrial fibrillation (AF) according to the types defined by Wells usually resorts to the visual inspection of bipolar intraatrial electrograms. The focus of this study was to test seven parameters aimed to quantify the degree of organization of the electrograms, and then to design a final classification scheme based on a multidimensional, minimum-distance analysis. The following parameters were tested: mean atrial period (AP) and its coefficient of variation (CV); number of points lying at the baseline (NO) and the Shannon entropy (EN) of the amplitude probability density function (APDF); depolarization width (F-WIDTH); and correlation waveform analysis (CWA) and electrogram bandwidth (BW). The signal database consisted in a set of 160 AF strips of Type I, II, and III AF, scored by an expert cardiologist (60 Type I, 40 Type II, 60 Type III) and further divided in a training set (60) and a test set (100). Strips were 6 seconds long and were recorded with 5-mm interspace bipolar catheters from electrically induced (n = 13) and chronic (n = 10) patients. A classification algorithm based on a minimum-distance (Mahalanobis distance) discriminant analysis was tested. Using a single parameter, the best discriminations were provided by NO, F-WIDTH, and CV. F-WIDTH was found strongly inversely correlated to NO (r = -0.90). Of all the two-parameter combinations, CV-NO provided the best classification: 92 of 100 segments were correctly classified with sensitivity > 90% and specificity > 92%. A further improvement was obtained by including BW as a third parameter (93/100 correctly classified). The use of more than three parameters not only failed to improve, but even degraded the classification.

Algorithms↗
PubMed1998

Pitfalls in the economic evaluation of thrombolysis in myocardial infarction. The impact of national differences in the cost of thrombolytics and of differences in the efficacy across patient subgroups.

BACKGROUND: The economic evaluation of the results of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Artery (GUSTO) trial found that recombinant tissue plasminogen activator is more cost-effective than streptokinase for the treatment of acute myocardial infarction. AIM: We evaluated the impact on a cost effectiveness analysis, of the differences in the cost of thrombolytics among countries and of differences in efficacy across patient subgroups. METHODS: We considered the crude costs of streptokinase and recombinant tissue plasminogen activator in Germany, Italy, the United Kingdom, and the United States of America, and the 30-day mortality found in the GUSTO trial. We calculated the incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen activator. We also calculated the incremental costs for each life saved for two protocols implying a selective use of streptokinase and recombinant tissue plasminogen activator (age-selective protocol: recombinant tissue plasminogen activator in patients < or = 75 years, streptokinase in older patients; site-selective protocol: recombinant tissue plasminogen activator in anterior acute myocardial infarction, streptokinase in non-anterior acute myocardial infarction). RESULTS: The incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen activator in all GUSTO patients vary greatly among countries: the incremental costs for each life saved are 31%, 45%, and 97% higher in Germany, Italy, and the United States of America compared to the United Kingdom. The use of a site-selective protocol implies a halved cost-effectiveness ratio compared to the use of recombinant tissue plasminogen activator in all cases of acute myocardial infarction. CONCLUSIONS: (1) The cost-efficacy of recombinant tissue plasminogen activator vs streptokinase in acute myocardial infarction varies greatly among countries due to differences in the cost of drugs. (2) A selective use of thrombolytics for some sites of infarction is more cost-effective than the exclusive use of recombinant tissue plasminogen activator.

Aged↗
PubMed1998

A cost-effectiveness analysis of aspirin versus oral anticoagulants after acute myocardial infarction in Italy -- equivalence of costs as a possible case for oral anticoagulants.

AIMS: The recent publication of two large trials of secondary prevention of coronary artery disease with oral anticoagulants (WARIS and ASPECT) has caused a revival of the interest for this antithrombotic therapy in a clinical setting where the use of aspirin is common medical practice. Despite this, the preferential use of aspirin has been supported by an American cost-effectiveness analysis (JAMA 1995; 273: 965). METHODS AND RESULTS: Using the same parameters used in that analysis and incidence of events from the Antiplatelet Trialists Collaboration and the ASPECT study, we re-evaluated the economic odds in favor of aspirin or oral anticoagulants in the Italian Health System, which differs significantly in cost allocation from the United States system and is, conversely, similar to other European settings. Recalculated costs associated with each therapy were 2,150 ECU/ patient/year for oral anticoagulants and 2,187 ECU/patient/year for aspirin. In our analysis, the higher costs of oral anticoagulants versus aspirin due to a moderate excess of bleeding (about 10 ECU/ patient/year) and the monitoring of therapy (168 ECU/ patient/year) are more than offset by an alleged savings for recurrent ischemic syndromes and interventional procedures (249 ECU/ patient/year). CONCLUSIONS: Preference of aspirin vs. oral anticoagulants in a pharmaco-economical perspective is highly dependent on the geographical situation whereupon calculations are based. On a pure cost-effectiveness basis, and in the absence of data of direct comparisons between aspirin alone versus I.N.R.-adjusted oral anticoagulants, the latter are not more expensive than aspirin in Italy and, by cost comparisons, in other European countries in the setting of post-myocardial infarction.

Administration, Oral↗
PubMed1997

Intravenous nitrates in the prehospital management of acute pulmonary edema.

STUDY OBJECTIVE: We sought to assess the effect of nitrates on prehospital mortality among patients with acute pulmonary edema (APE). METHODS: The study involved a retrospective evaluation of the records of prehospital outcome in 640 patients with APE rescued by the mobile CCU (MCCU) of Florence, Italy, between January 1980 and December 1991. The MCCU serves an urban environment with a population of 400,000 in a 102-sq km area. In the years 1980 through 1983, patients were treated with oxygen, morphine, furosemide, digoxin, nitrates, aminophylline, or dopamine, according to the attending physician's judgment. From 1984 through 1991, new guidelines for the use of intravenous nitrates, based on differential treatment according to blood pressure, were in use. RESULTS: Overall prehospital mortality rate for APE in all patients was 7.8% (50 of of 640 patients). Mortality after 1984 was significantly lower than before (5.3% versus 13%, P < .01). Nitrates were effective in reducing mortality, even in hypotensive patients. Multivariate analysis showed that outcome was significantly affected by two clinical features (dyspnea and low blood pressure), treatment with nitrates, and calendar period effects (before/after 1984). CONCLUSION: Our findings suggest that the use of intravenous nitrates improves short-term prognosis in APE.

Acute Disease↗
PubMed1997

Tissue factor and plasminogen activator inhibitor type 2 expression in human stimulated monocytes is inhibited by heparin.

Stimulated monocytes are involved in blood clotting and fibrin dissolution by synthesizing tissue factor (TF) and fibrinolytic components such as plasminogen activator inhibitor type 2 (PAI-2). Heparin interacts with smooth muscle cells, platelets, and endothelial cells and specifically binds to human monocytes. In endothelial and smooth muscle cells, heparin selectively inhibits collagenase and tissue plasminogen activator gene expression. To investigate (1) heparin's influence on the hemostatic system by its interactions with plasma factors and cellular elements and (2) to determine its effects on gene expression in blood circulating cells, we studied the effect of heparin on TF and PAI-2 protein and mRNA in human lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-stimulated monocytes. TF and PAI-2 proteins were investigated by ELISA and by assaying procoagulant activity. The mRNA study was carried out by an initial PCR screening followed by a Northern blot semiquantitative analysis. Heparin (0.5 U/mL) inhibited both TF and PAI-2 production and gene expression. The contemporaneous protein and mRNA decrease (TF and PAI-2 protein 22 and 42%, respectively; suggests that this action is, at least partially, at the transcriptional level. The effect is not specific for heparin and is not demonstrated by other glycosaminoglycans (chondroitin-4-sulfate or dermatan sulfate). This action may be relevant for the antithrombotic activity of heparin in cell-mediated blood clotting activation.

Anticoagulants↗
PubMed1997

[Evaluation of the cost-effectiveness of thrombolytic therapy in acute myocardial infarct using tissue plasminogen activator or streptokinase:the Italian perspective].

UNLABELLED: The GUSTO trial demonstrated that tPA is more effective than streptokinase in the therapy for acute myocardial infarction (AMI). Although tPA is much more expensive than streptokinase some recent analyses have demonstrated that the use of this drug is also cost-effective. However, the cost of the two drugs is different in Italy and USA. Moreover, the difference of the efficacy of the two drugs varies greatly among subgroups of patients with AMI. The aim of this study was to assess the cost-effectiveness of the exclusive use of tPA and streptokinase in the general population and in subgroups of patients divided according to age and site of AMI, using the costs of the drugs in Italy (streptokinase 100,600 and tPA 1,524,300 Italian Liras (ItL)/treatment). METHODS: The results of the GUSTO trial (30 day-mortality) obtained in the general population and subgroups (< or = 75 years and > 75 years; anterior AMI and non-anterior AMI) were applied to patients enrolled in the GISSI-2 trial. The number of lives saved and the incremental costs for each life saved were calculated for the use of tPA in respect to the use of streptokinase. Results are referred to the treatment of 1000 patients. RESULTS: In the general population, in respect to the use of streptokinase, the use of tPA would save 10 lives at an incremental cost of 142.370 millions ItL/life saved. The use of tPA in patients aged < or = 75 years would save 11 patients at the incremental cost of 129.427 millions ItL/life saved, while the use of tPA in patients aged > 75 years would save 13 patients at the incremental cost of 109.515 millions ItL/life saved. In anterior AMI, tPA can save 19 patients at the additional cost of 74.932 millions ItL/life saved, while in non-anterior AMI it can save 6 patients at the additional cost of 237.238 millions ItL/life saved. A subgroup analysis demonstrated that 9 lives can be saved with the use of tPA in anterior AMI and streptokinase in non-anterior AMI at the cost of 49.038 millions ItL/life saved, in respect to the exclusive use of streptokinase. CONCLUSIONS: 1. The cost-effectiveness ratio of tPA in the general population with AMI is comparable to that of other expensive therapies (< 150 millions ItL/life saved). 2. However, a strategy implying a selective use of the two drugs is far more cost-effective (< 50 millions ItL/life saved).

Aged↗
PubMed1996

Platelet and blood clotting activation in patients with mitral valve prolapse.

In patients with mitral valve prolapse (MVP) a high incidence of valvular abnormalities with a history of previous cerebrovascular disease has been reported and an embolic mechanism has been proposed. Aim of this study is the study of platelet and coagulation activation in patients with MVP. Fifty-four patients affected by MVP (mean age 46 +/- 15 yrs, 22 males, 32 females) and 50 control subjects, age- and sex-matched, were tested for platelet activation [P-selectin and GpIIb-IIIa platelet surface expression at rest and after stimuli by flow cytometric analysis, Beta-Thromboglobulin (TG) and Platelet Factor 4 (PF4) plasma levels by ELISA, platelet-rich-plasma (PRP) and whole blood spontaneous platelet aggregation (SPA)] and for activation of blood coagulation (Prothrombin activation fragment F1+2 plasma levels by ELISA). P-selectin, GpIIb-IIIa expression, Beta-TG, PF4 and SPA were found similar in MVP patients and in controls. However, in patients with severe mitral regurgitation (MR) the percentage of activated platelets which express P-selectin after stimuli was slightly but significantly (p < 0.05) lower in comparison to MVP patients without or with mild to moderate MR and to controls. Moreover, in patients with severe MR F1+2 levels (median 1.6 nmol/L, range 0.6-2.6 nmol/L) were significantly higher (p < 0.001) than both in controls (median 0.95 nmol/L, range 0.2-1.4 nmol/L) and in patients without or with mild to moderate MR (median 1.0 nmol/L, range 0.4-2.3 nmol/L). Our findings suggest that MVP is not responsible per se for blood clotting activation, but in patients with severe mitral insufficiency an increase in thrombin generation can occur. These alterations in hemostatic system may represent a mechanism by which MR increases the risk of thromboembolic events in patients with MVP.

Adenosine Diphosphate↗
PubMed1996

Noninvasive evaluation of right ventricle systolic pressure during dynamic exercise by saline-enhanced Doppler echocardiography in progressive systemic sclerosis.

Progressive systemic sclerosis (PSS) is characterized in its first phases by vascular damage. Lungs are involved in two thirds of patients with initial progressive destruction of the capillary bed and consequent reduction of the functional reserve, which may lead to hypertension of the pulmonary circulation. For these reasons it is of great interest to have early information about the pressure of the pulmonary circulation, both at rest and during exercise, to follow the progression and the evolution of the illness independently from subjective symptoms. The aim of the study was to evaluate by a noninvasive method, saline-enhanced Doppler echocardiography, the behavior of the right ventricular systolic pressure in patients with PSS, at rest and during exercise, without clear instrumental or clinical signs of pulmonary involvement at rest. Nine patients (7 women and 2 men) with PSS, aged 55.7 +/- 8.7 years, and 9 control subjects were evaluated. All patients had normal pulmonary pressure at rest and negative history for effort dyspnea. Subjects underwent Doppler echocardiographic examination at rest and during exercise. Right ventricular systolic pressure was evaluated by saline-enhanced Doppler technique, at rest and throughout exercise. At rest the right ventricular systolic pressure was normal in all patients and controls. At the end of exercise, in 4 patients, values were still normal (40.7 +/- 2.2 mmHg); in the others pathologic values were recorded (59.8 +/- 3.9 mmHg). In the control group values were always normal (35.6 +/- 4.6 mmHg). In our study the saline-enhanced Doppler echocardiography has been demonstrated to be an important diagnostic tool for the noninvasive evaluation of right ventricular systolic pressure, both at rest and during exercise; it could be useful in monitoring the pulmonary vascular damage in patients with PSS.

Adult↗
PubMed1996

[Oxygen therapy and pulmonary hypertension in chronic obstructive bronchopneumopathies].

Pulmonary hypertension has a negative prognostic value in the progression of chronic obstructive lung disease. The hypoxic vasoconstriction and subsequent morphological alterations that occur in the small arteries and in the pre-capillary arterioles may contribute to the reduction of the pulmonary vascular bed. The evolution of pulmonary hypertension in patients with chronic obstructive lung disease is not rapid except during relapses of the disease. Oxygen therapy reduces pulmonary arterial pressure values not only via a reduction in the functional abnormalities of the vessels but also via a regression in the anatomic changes induced by hypoxemia. Thus, long-term oxygen therapy may slow the progression of pulmonary hypertension in the course of chronic obstructive lung disease and the longer is oxygen administration the better haemodynamic results are obtained. The Medical Research Council (MRC) Study and the Nocturnal Oxygen Therapy Trial (NOTT) have clearly demonstrated that mortality among hypoxiemic patients treated with low-flow oxygen therapy is reduced; the NOTT also reported a reduction of about 10% in the levels of pulmonary vascular resistances in patients treated with long-term oxygen therapy, while an increase of about 7% has been observed in patients treated with oxygen therapy only during the night. Nevertheless, the reduction of mortality observed during long-term oxygen therapy not always is accompanied by an haemodynamic improvement; in particular a reduction in the pulmonary arterial pressure seems not to reduce mortality. In conclusion long term oxygen therapy may slow the progression of pulmonary hypertension during chronic obstructive lung disease while the improvement in pulmonary haemodynamic due to oxygen therapy is not strictly correlated with a reduction of mortality.

Hemodynamics↗
PubMed1996

[Anticoagulant or antiaggregant therapy in the secondary prevention of myocardial infarct?].

The recent publication of the results of two large trials of secondary prevention of myocardial infarction with oral anticoagulants is causing a revival of interest for oral anticoagulants in this clinical setting. On the basis of these data, oral anticoagulants should be considered not only an effective preventive strategy, but, probably, more effective than antiplatelet agents, currently the standard therapy in the prevention of thrombosis in acute myocardial infarction. There are advantages and disadvantages for both these treatments, and an adequate balancing of expected risks and benefits has to be performed in each single patient. The present review summarizes rationales and main clinical results in the prevention of reinfarction with antiplatelet agents and with oral anticoagulants, and analyzes the reasoning to prefer the formers or the latters in daily clinical practice of secondary prevention of coronary artery disease. Also, an analysis of the benefit/risk ratio of antiplatelet agents (aspirin) and oral anticoagulants in the Italian health system is synthetically presented. Such an analysis can be useful for the formulation of general guidelines and may suggest a modification of currently established and widely popular therapeutic habits in the management of coronary artery disease in Italy.

Administration, Oral↗
PubMed1989

Competitive inhibition of platelet thromboxane A2 receptor binding by picotamide.

On the basis of indirect pharmacological evidence, picotamide, a methoxy derivative of 4-hydroxy-isophthalic acid (N,N'bis(3-picolyl)-4-methoxy-isophthalamide) has been postulated to inhibit platelet aggregation by competitively interfering with the thromboxane A2 (TxA2) platelet receptor. In the present study the interaction between picotamide and TxA2 receptors on human platelets was investigated by a direct radioligand assay method with [125I]PTA-OH and [3H]U46619 as labelled radioligands. The ONO11120 and U46619 inhibitory constants (Ki) for [125I]PTA-OH binding were 19 +/- 4 and 17 +/- 3 nM, respectively. Picotamide displaced [125I]PTA-OH binding with a Ki of 1472 +/- 321 nM. The Ki for ONO 11120 and U46619 on [3H]U46619 binding were 42 +/- 12 and 16 +/- 5 nM, respectively, whereas the Ki for picotamide was 1648 +/- 431 nM. These data provide evidence that picotamide can directly inhibit the TxA2 platelet receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

Comparison of the acute hemodynamic effects of intravenous celiprolol and propranolol in patients with suspected coronary disease.

The acute hemodynamic effects of intravenously administered celiprolol and propranolol were compared in 18 patients, 12 with coronary obstruction in the presence or absence of reduced LV function and six with no significant cardiac disease. The study was performed using a single blind, randomized design with celiprolol (0.07 and 0.14 mg/kg) and propranolol (0.07 mg/kg) in six patients per treatment group. The hemodynamic parameters obtained via right and left heart catheterization were measured at baseline and at 5 and 10 min after drug infusion (1.0 mg/min). Propranolol produced a significant fall in left ventricular Vmax, left ventricular dP/dt and cardiac output. In contrast, celiprolol either caused no change or significantly increased these parameters. These results indicate that celiprolol has an acute hemodynamic profile which differs significantly from that of propranolol.

Adult↗
PubMed1983

A systemic hemodynamic evaluation of indapamide.

The hemodynamic effects of indapamide were evaluated in an open clinical trial of nine patients with mild to moderate hypertension. Hemodynamic and echocardiographic measurements were made before and after six weeks of treatment with single daily doses of 2.5 mg of indapamide. Indapamide significantly reduced the mean standing systolic blood pressure (P less than 0.025), the mean standing diastolic blood pressure (P less than 0.01), the mean arterial blood pressure (P less than 0.001), and the mean total peripheral vascular resistance (P less than 0.01). Cardiac output increased 12% (P less than 0.05) during treatment. The heart rate, left ventricular end-diastolic and end-systolic volumes, systolic volume, and ejection fraction were not markedly altered after treatment with indapamide, although the systolic wall stress index fell slightly. Six weeks of indapamide administration was well tolerated with no notable adverse effects of the drug. The results suggest that indapamide reduces arterial blood pressure in hypertensive patients by decreasing total peripheral resistance.

Adult↗