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Biomedical subjects

G G Serneri

Publications and source records attributed to G G Serneri.

At least 19 recordsLinked to original sources
PubMed2001

Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular function.

In 76 patients with heart failure (HF) (New York Heart Association [NYHA] classes I through IV) and in 15 control subjects, cardiac angiotensin II (Ang II) generation and its relationship with left ventricular function were investigated by measuring aorta-coronary sinus concentration gradients of endogenous angiotensins and in a part of patients by studying (125)I-labeled Ang I kinetics. Gene expression and cellular localization of the cardiac renin-angiotensin system components, the density of AT(1) and AT(2) on membranes and isolated myocytes, and the capacity of isolated myocytes for synthesizing the hypertrophying growth factors insulin-like growth factor-I (IGF-I) and endothelin (ET)-1 were also investigated on 22 HF explanted hearts (NYHA classes III and IV) and 7 nonfailing (NF) donor hearts. Ang II generation increased with progression of HF, and end-systolic wall stress was the only independent predictor of Ang II formation. Angiotensinogen and angiotensin-converting enzyme mRNA levels were elevated in HF hearts, whereas chymase levels were not, and mRNAs were almost exclusively expressed on nonmyocyte cells. Ang II was immunohistochemically detectable both on myocytes and interstitial cells. Binding studies showed that AT(1) density on failing myocytes did not differ from that of NF myocytes, with preserved AT(1)/AT(2) ratio. Conversely, AT(1) density was lower in failing membranes than in NF ones. Ang II induced IGF-I and ET-1 synthesis by isolated NF myocytes, whereas failing myocytes were unable to respond to Ang II stimulation. This study demonstrates that (1) the clinical course of HF is associated with progressive increase in cardiac Ang II formation, (2) AT(1) density does not change on failing myocytes, and (3) failing myocytes are unable to synthesize IGF-I and ET-1 in response to Ang II stimulation.

Analysis of Variance↗
PubMed2000

Selective upregulation of cardiac endothelin system in patients with ischemic but not idiopathic dilated cardiomyopathy: endothelin-1 system in the human failing heart.

Only scarce information is available on the activity and modifications of the cardiac endothelin (ET)-1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro-ET-1 (ppET-1), ET-converting enzyme-1, and ET(A) and ET(B) receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription-polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ET(A) and ET(B) receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P<0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ET(A) mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ET(B) mRNA was almost exclusively localized on nonmyocyte cells. ET(A)- and ET(B)-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r=0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.

Adult↗
PubMed2000

Renal endothelin in heart failure and its relation to sodium excretion.

BACKGROUND: Recent studies have shown that endothelin-1 (ET-1) antagonists increase sodium excretion and improve renal blood flow in experimental heart failure (HF). However, despite a number of investigations that have reported a significant increase in ET-1 plasma levels in patients with HF, it is still not known whether increased renal synthesis and urinary excretion of ET-1 occur. Our aim was to investigate renal ET-1 formation and its relation to sodium excretion in patients with HF. METHODS: One hundred forty-seven patients with HF, subdivided according to New York Heart Association (NYHA) functional classes, and 28 healthy controls were studied. ET-1 and big ET-1 were measured in plasma and in 24-hour urine by radioimmunoassay. Atrial and brain natriuretic peptide, arginine vasopressin, plasma renin activity, and hemodynamic variables were also investigated. RESULTS: Urinary ET-1 excretion was already increased in NYHA class II patients (P <.001 vs controls), whereas plasma ET-1 increased only in NYHA class III and IV patients (P <.001). In the 71 subjects who were not receiving diuretic treatment, urinary ET-1 was selected as the strongest predictor of sodium excretion by multivariate stepwise analysis. CONCLUSIONS: Urinary ET-1 excretion increases in an earlier phase of HF than plasma ET-1 and appears to be closely correlated with sodium excretion, indicating renal ET-1 is a target for ET-1 antagonists in patients with HF.

Aged↗
PubMed2000

Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy.

To investigate the time sequence of cardiac growth factor formation, echocardiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-like growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Relative peptide formation was also measured by radioimmunoassay. In pressure overload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 times vs. sham at 3 h and 112 times at 6 h, respectively) was followed by recovery (12 h) of initially decreased (0.5-6 h) myocardial contractility. In volume overload, contractility was not decreased, the angiotensinogen gene was slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpressed. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pressure overload (14 times and 37 times, respectively). In the latter setting, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth factor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardial hypertrophy.

Adaptation, Physiological↗
PubMed1999

Cardiac growth factors in human hypertrophy. Relations with myocardial contractility and wall stress.

The aim of the present study was to investigate whether and which cardiac growth factors are involved in human hypertrophy, whether growth factor synthesis is influenced by overload type and/or by the adequacy of the hypertrophy, and the relationships between cardiac growth factor formation and ventricular function. Cardiac growth factor formation was assessed by measuring aorta-coronary sinus concentration gradient in patients with isolated aortic stenosis (n=26) or regurgitation (n=15) and controls (n=12). Gene expression and cellular localization was investigated in ventricular biopsies using reverse transcriptase-polymerase chain reaction and in situ hybridization. Cardiac hypertrophy with end-systolic wall stress <90 kdyne/cm2 was associated with a selective increased formation of insulin-like growth factor (IGF)-I in aortic regurgitation and of IGF-I and endothelin (ET)-1 in aortic stenosis. mRNA levels for IGF-I and preproET-1 were elevated and mainly expressed in cardiomyocytes. At stepwise analysis, IGF-I formation was correlated to the mean velocity of circumferential fiber shortening (r=0.86, P<0.001) and ET-1 formation to relative wall thickness (r=0.82, P<0. 001). When end-systolic wall stress was >90 kdyne/cm2, IGF-I and ET-1 synthesis by cardiomyocytes was no longer detectable, and only angiotensin (Ang) II was generated, regardless of the type of overload. The mRNA level for angiotensinogen was high, and the mRNA was exclusively expressed in the interstitial cells. Ang II formation was positively correlated to end-systolic stress (r=0.89, P<0.001) and end-diastolic stress (r=0.84, P<0.001). Multivariate stepwise analysis selected end-systolic stress as the most predictive variable and left ventricular end-diastolic pressure as the independent variable for Ang II formation (r=0.93, P<0.001). In conclusion, the present results indicate that the course of human left ventricular hypertrophy is characterized by the participation of different cardiac growth factors that are selectively related both to the type of hemodynamic overload and to ventricular function.

Aged↗
PubMed1999

Impaired adaptation of cardiopulmonary receptors to Western diet in normotensive black immigrants.

A blood pressure increase was reported in black immigrants from Africa to Western countries. The present study was undertaken to evaluate whether an impairment of the cardiopulmonary reflex might make blacks unable to adapt peripheral vascular resistance to increased sodium intake. Ten normotensive clinically healthy blacks (aged 38+/-6 years) who had recently migrated from Mogadishu, Somalia to Florence and 10 age- and gender-matched healthy white subjects were investigated. Cardiopulmonary baroreceptor reflex was studied after 7 days of normal (108 mEq) and low (30 mEq) sodium intake by assessing forearm vascular resistance (FVR) and central venous pressure (CVP) during the application of lower body negative pressure (LBNP) at -10 and -20 mm Hg. With a normal sodium diet the gain in cardiopulmonary baroreceptor reflex, expressed as the FVR increase per mm Hg of CVP reduction, was significantly lower in blacks than in white subjects (2.6+/-1.1 v 5.1+/-1.1 U per mm Hg of CVP, P < .001). Differences between the groups disappeared with a low-sodium diet because the reduction of the efficiency of the cardiopulmonary baroreceptor reflex was lower in blacks than in whites (2.4+/-0.7 v 3.3+/-0.7 U per mm Hg of CVP, P = .09). In conclusion, the efficiency of the cardiopulmonary reflex is lower in normotensive black immigrants than in whites. The lower adaptation of the cardiovascular system to the Western sodium diet could contribute to reported long-term blood pressure increase.

Adaptation, Physiological↗
PubMed1999

Decreased baroreflex sensitivity assessed from phase IV of Valsalva maneuver in mild congestive heart failure.

Decreased sensitivity of cardiopulmonary and arterial baroreceptors has been hypothesized to sustain sympathetic activation in patients with heart failure. In the present investigation the relationship between the impairment of baroreflex sensitivity and clinical severity of congestive heart failure was investigated. The authors studied 58 patients with heart failure (14 in NYHA class I, 22 in NYHA class II, and 22 in NYHA class III), 38 women and 20 men, age range 28-65 years. Thirty-two patients suffered from idiopathic dilated cardiomyopathy and 26 from coronary heart disease. As control group they examined 21 age-matched subjects. Baroreceptor sensitivity was studied by using the Valsalva maneuver as stimulus. Arterial pressure and heart rate were measured noninvasively by Finapres instrument (Ohmeda) and signals were recorded and elaborated with a personal computer. A decrease of baroreflex sensitivity was already demonstrable in NYHA class I patients (4.72 +/- 3.31 vs 9.25 +/- 5.05 msec/mm Hg in control group) (p < 0.005). A further impairment of baroreceptor response was found in patients in NYHA class II (1.94 +/- 2.88 msec/mm Hg, p < 0.001) and class III (1.78 +/- 1.52 msec/mm Hg, p < 0.001). Baroreceptor response showed a significant correlation with functional NYHA class (r = 0.61, p < 0.001) and anaerobic threshold (r = 0.57, p < 0.001) while the correlation was less tight with left ventricular end-diastolic diameter, fractional shortening, left ventricular ejection fraction, pulmonary mean arterial blood pressure, cardiac index, distance at 6 minutes walk corridor test, and maximal oxygen consumption (VO2max). These results suggest that baroreceptor function may be impaired early in the clinical course of heart failure and may contribute to sympathetic activation.

Adult↗
PubMed1998

Effect of low-dose heparin on fibrinogen levels in patients with chronic ischemic heart disease.

Several prospective studies have demonstrated that high plasma fibrinogen levels are associated with an increased risk of ischemic heart disease. Since in most patients an increased thrombin generation has been reported, we investigated whether the control of thrombin generation could affect plasma fibrinogen levels. Forty male outpatients (20 asymptomatic with previous myocardial infarction and 20 with stable effort angina) were enrolled in a randomized medium-term (6 months) cross-over study. Clottable fibrinogen, according to Clauss, prothrombin fragment 1 + 2, thrombin-antithrombin complex, and fibrinopeptide A were evaluated in relation to treatment with low-dose heparin. After a 15-day wash-out period, during which patients had been treated only with nitrates if needed, patients were allocated to two sequential periods of treatment with standard heparin (12,500 U, subcutaneously daily) plus antianginal treatment or antianginal treatment alone, separated by a second 15-day wash-out period. At the end of the treatment period with low-dose heparin significant decreases in the plasma fibrinogen (2.5 +/- 0.6 g/l vs. 3.3 +/- 0.5 g/l, P < 0.001), prothrombin fragment 1 + 2 (1.4 +/- 0.5 nmol/l vs. 1.9 +/- 0.7 nmol/l, P < 0.001), thrombinantithrombin (4.5 +/- 2.4 ng/ml vs. 9.7 +/- 3.6 ng/ml, P < 0.001), and fibrinopeptide A (2.1 +/- 1.1 ng/ml vs. 3.5 +/- 2.1 ng/ml, P < 0.001) were observed compared with the period without heparin. The present results indicate that low-dose heparin can effectively control the increased abnormal thrombin generation and elevated fibrinogen levels in patients with ischemic heart disease, possibly decreasing the risk of cardiovascular death.

Aged↗
PubMed1998

Increased renal endothelin formation is associated with sodium retention and increased free water clearance.

To investigate whether renal endothelin (ET)-1 participates in water and sodium handling, we investigated the influence of different sodium intakes on renal production of ET-1 in eight healthy subjects. The functional relationship with the renin-angiotensin system was also studied. Renal ET-1 formation is affected by sodium intake, because 1 wk of high sodium decreased urinary ET-1 excretion (-34%, P < 0.05), whereas a low-sodium diet increased ET-1 excretion (66%, P < 0.05) and mRNA expression for preproendothelin-1 in epithelial cells of medullary collecting ducts and endothelial cells of the peritubular capillary network. Increased ET-1 renal synthesis was associated with sodium retention and increased free water clearance. Urinary ET-1 excretion changes from normal to low-sodium diet were negatively related to contemporary changes in sodium excretion (r = 0.97, P < 0.05) and were positively correlated with free water clearance (r = 0.97, P < 0.05). These correlations were maintained during angiotensin-converting enzyme inhibition, which only partially reduced ET-1 renal excretion. These results indicate that renal ET-1 production is indeed modulated by varying sodium intakes and may exert a role in sodium and water handling.

Adult↗
PubMed1996

Age-related and vasomotor stimuli-induced changes in renal vascular resistance detected by Doppler ultrasound.

Indirect measurement of renal vascular resistance by duplex Doppler waveform analysis was evaluated in relation to aging and some pathophysiological conditions. Baseline renal resistive index (RRI) (peak systolic frequency shift - lowest diastolic frequency shift/peak systolic frequency shift) was measured in healthy controls aged 20 to 85 years by analyzing the blood flow velocity waveform of interlobar arteries. RRI changes induced by sympathetic activation (cold pressor test and handgrip test) or by fluid load were evaluated. Both repeatability and reproducibility were very good, as the intra and interoperator variations were all less than their reproducibility coefficients. RRI showed a significant increase with aging (ANOVA P < .001), particularly evident in subjects older than 50 years. Both the cold pressor test and handgrip test induced in all the subjects (n = 16) a significant increase in RRI (P < .001), from 0.59 +/- 0.04 to 0.69 +/- 0.04 (12 +/- 6%) for the cold pressor test and from 0.57 +/- 0.03 to 0.66 +/- 0.03 (15 +/- 2%) for the handgrip test. In eight subjects intravenous fluid load (0.25 mL/kg/min of 0.9% NaCl for 120 min) caused a significant decrease in RRI (P < .001), from 0.62 +/- 0.02 to 0.53 +/- 0.01 (17 +/- 2%), which was inversely related to mean blood pressure rise (r = 0.71, P < .001). These data show that pulsed wave Doppler analysis is an accurate method for an indirect evaluation of changes in renal vascular resistance induced by common vasomotor stimuli.

Adult↗
PubMed1995

Effect of n-3 fatty acid ethyl ester supplementation on fatty acid composition of the single platelet phospholipids and on platelet functions.

Twenty healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 polyunsaturated fatty acids (PUFA) ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 months, followed by a 3-month wash-out period. Fatty acids of platelet phospholipid fractions, platelet aggregation, and thromboxane B2 (TXB2) formation were analyzed at 0, 2, and 4 months of treatment and at 1, 2, and 3 months of wash-out. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were markedly increased after 2 months, with slight differences in further accumulation up to 4 months among the various phospholipid fractions. Significant decreases in platelet sensitivity to collagen, serum TXB2 levels, and urinary TXB2 metabolites were also observed following n-3 PUFA treatment. During the first and second month of wash-out, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 months of wash-out, alterations were no longer detectable with respect to pretreatment values. After 3 months of wash-out, platelet function parameters also were returned to baseline. Thus, both platelet lipids and function are influenced by n-3 PUFA ethyl ester supplementation, and significant alterations are still detectable after 2 months of wash-out.

Adult↗
PubMed1995

Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis.

This study of seven healthy young subjects was designed both to establish whether endothelin-1 (ET-1) is involved in the homeostasis of blood volume and to clarify the relationship between plasma and urinary ET-1. Acute volume expansion (+17%) caused increases in venous blood pressure (+4.4 mmHg) and the plasma concentration of ET-1 (+129%) and a decrease (-99%) in the urinary excretion of ET-1. Volume depletion (-8.5%) provoked an increase in the plasma concentration of ET-1 without altering the urinary excretion of ET-1. Passive elevation of an arm resulting in a local decrease of venous blood pressure (-17 mmHg) elicited an increase of the local formation of ET-1, with a 10-fold increase in the venous-arterial gradient compared with the opposite arm, which lay at the level of the heart. The increased local formation of ET-1 was blunted by volume expansion. The results indicate that 1) plasma ET-1 and urinary ET-1 represent two different endothelin-generating systems, both of which are involved in the regulation of blood volume, and 2) plasma ET-1 appears to be an important mechanism for the long-lasting adaptations of venous wall tension to changes in blood volume.

Adult↗
PubMed1994

Changes in blood pressure reactivity and 24-hour blood pressure profile occurring at puberty.

To evaluate blood pressure reactivity in children and its changes in adolescents, the acute pressor response to a video-game stress test and the noninvasive ambulatory blood pressure monitoring were evaluated in 62 healthy children divided into three age groups. Basal blood pressure values were measured according to the NIH Task Force. With baseline measures and body mass index controlled for, analysis of covariance showed that the video game provoked significant and incremental cardiovascular reactivity across the games in adolescents when compared with the two other groups of children. The same group of children showed also a significantly higher systolic ambulatory pressure during the daytime, whereas no significant difference was observed by basal BP measurement. In conclusion an increased reactivity to external stimuli was observed in adolescents, and this pattern was strictly associated with a higher daily blood pressure.

Adolescent↗
PubMed1992

Transient intermittent lymphocyte activation is responsible for the instability of angina.

BACKGROUND: Blood clotting activation is an important component of the inflammatory response; the outbursts of unstable angina are usually associated with increased thrombin formation and coronary mural thrombosis. METHODS AND RESULTS: To investigate 1) whether monocyte activation is responsible for the enhanced thrombin formation during bursts of unstable angina and 2) what mechanism(s) might be responsible for monocyte activation, we studied patients with unstable angina (n = 31), stable effort angina (n = 23), left endoventricular thrombosis (n = 8), and control subjects (n = 44), measuring plasma fibrinopeptide A (FPA) levels and the capacity of monocytes to express procoagulant activity (PCA) and of lymphocytes to modulate this expression. Patients with unstable angina and patients with endoventricular thrombosis had significantly (p less than 0.0001) higher FPA plasma levels than patients with effort angina and control subjects. However, only monocytes from unstable angina patients expressed significantly increased PCA characterized as tissue factor-like activity (units/10(5) monocytes, median and range; 120, 1.1-463.2 versus 10.8, 0.8-39.1 in control subjects; p less than 0.0001 versus the other groups). When 14 patients with unstable angina were restudied 8-12 weeks later, they showed neither elevated plasma FPA levels nor monocyte PCA. In unstable angina patients, there was a correlation between FPA and PCA (r = 0.56, p less than 0.001). For expression of PCA by monocytes, both an incubation of at least 2 hours with lymphocytes and direct monocyte-lymphocyte contact were needed. In reconstitution and cross-mixing experiments, only lymphocytes from patients with active unstable angina induced the expression of PCA by monocytes from both control and patient groups. CONCLUSIONS: The results demonstrate that the increased thrombin formation in unstable angina patients is due to the expression of tissue factor-like activity by activated monocytes. The monocyte activation appears to be a part of a lymphocytic cell-instructed response intermittently triggered by unknown factors.

Aged↗
PubMed1990

Transcutaneous oximetry monitoring during the early phase of exercise in patients with peripheral artery disease.

The present work was performed to test the sensitivity of transcutaneous oximetry in evaluating the first stage of peripheral artery disease in patients with few symptoms. Eighteen nondiabetic patients, stage II according to Fontaine and classified according to their walking capability and Doppler examination, were investigated. Ten healthy subjects served as controls. Measurements were performed with the subjects standing and during exercise on a treadmill. Postischemic hyperemia was also evaluated with strain-guage plethysmography. Standing values did not discriminate between patients and controls; on the contrary the pattern of the early phase of trancutaneous oximetry curves obtained during exercise allowed the investigators to distinguish the symptomatic patients with minimal symptoms. Accuracy and sensitivity of the method further increased when regional perfusion index was considered.

Blood Gas Monitoring, Transcutaneous↗
PubMed1990

Kinetic analysis of a TxA2 receptor antagonist. Evidence for the existence of an uptake system.

The kinetics of the binding of TxA2 and the characteristics of its putative uptake by platelets (plt) were investigated with a radiolabelled structural TxA2 analogue, 125I-PTA-OH, in platelets from 6 male healthy volunteers. The kinetic constants (Kobs, K1 and K-1) were calculated by time-course experiments according to Weiland and Molinoff. The affinity constant (Km) and maximal uptake velocity (Vmax) values for each subject were determined by the double-reciprocal plot of Lineweaver-Burk. The kinetically determined dissociation constant Kd was 10 nmol/l. In the uptake experiments a saturability of the association rate of the non-displaceable binding was observed at increased ligand concentration. Michaelis-Menten type kinetics were obtained and the Vmax was 32.44 fmol/10(8) plt x hour with a Km of 6.39 nmol/l. These observations suggest that the uptake was a carrier-mediated active transport.

Adult↗