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Biomedical subjects

G Finardi

Publications and source records attributed to G Finardi.

At least 73 records · Page 4Linked to original sources
PubMed1990

Metabolic effects of the combination of captopril and hydrochlorothiazide in hypertensive subjects.

The medium-term (16 weeks) effects of the combination of captopril and hydrochlorothiazide (HCTZ) on some metabolic indexes, particularly on plasma lipoproteins, were evaluated in 20 mild to moderate hypertensive outpatients. After a 4-week wash-out period, the subjects were given one tablet of a new commercially available fixed combination once/daily (i.e., captopril 50 mg + HCTZ 25 mg). The dose could be titrated to a maximum of one tablet twice daily according to individual blood pressure responses. Both systolic and diastolic blood pressure significantly decreased at week 4 and showed a further decrease thereafter; the rate of responders (diastolic blood pressure at or below 90 mm Hg at the end of the study) was very high (90%). The only metabolic change was a small though significant increase in HDL cholesterol (P less than .05), almost entirely due to an increase in the denser HDL3 subfraction. The atherogenic fractions, namely total cholesterol, LDL cholesterol, and apoprotein B, showed no significant changes. Plasma triglycerides underwent a transient increase at week 8 (P less than .05) but thereafter fell. Plasma glucose, creatinine, uric acid, and potassium were unchanged. The fixed combination of captopril and HCTZ seems highly effective in lowering blood pressure and seems devoid of untoward metabolic effects. Its overall impact on the coronary risk profile in hypertensive subjects seems therefore to be favorable.

Adult↗
PubMed1990

Autonomic nervous system and microcirculation in diabetes.

In order to evaluate the occurrence of sympathetic impairment of skin microvascular control in diabetes, we evaluated the spectral analysis of forearm skin laser-Doppler fluctuations in nine insulin-dependent diabetic subjects and in 21 controls of similar age. Low-frequency oscillations (around 0.1 Hz) were significantly lower in diabetics than in controls (2.333 +/- 0.340 (mean +/- SEM) units vs. 3.486 +/- 0.093 units, P less than 0.001), whereas no significant differences were found between the two groups regarding high-frequency respiration-related oscillations. These results suggest that the loss of rhythmicity in diabetic subjects is selectively related to low-frequency oscillations, mostly under sympathetic control, and is likely to be dependent on autonomic abnormality.

Adult↗
PubMed1990

Measuring left ventricular dimensions by conductance catheter in the rabbit.

A miniaturized (3.5 F), six-electrode conductance catheter was tested in 18 anaesthetized adult rabbits (weight 3.8-4.6 kg, ethylurethane 2.5 g kg-1). In eight animals, the reference stroke volume (ref-SV) was obtained by an electromagnetic flow probe, while reference end-diastolic volume (ref-LVEDV) was computed by dividing ref-SV by undamped thermal dilution ejection fraction (ref-EF) estimates. Comparisons with conductance indexes (z-SV, z-LVEDV and z-EF) were made at baseline, subsequent levels of graded haemorrhage and reinfusion state. In 10 animals intraventricular segmental conductance was compared with echocardiographic left ventricular cross-section (5 MHz short-focus probe), in the basal state and during acute left ventricular volume changes generated by inferior vena cava balloon occlusion. In each experiment, parallel conductance due to the tissues surrounding the left ventricle (Gp) was determined by infusing a 5M NaCl solution bolus into the right ventricle. Linear regression analysis showed fairly good correlations between z-SV, z-LVEDV and z-EF and reference indexes (r = 0.84, r = 0.83, and r = 0.72, respectively; P less than 0.001 in all cases). A linear regression analysis from 17 interventions (inferior vena cava balloon occlusion) showed a good correlation between left ventricular echocardiographic cross-sectional area and conductance, and higher correlation coefficients, r ranging from 0.870 to 0.986 were obtained from continuously sampled conductance and echographic measurements. Parallel conductance Gp was correlated (r = 0.807, P less than 0.01) with the intercept of the regression line of echographic vs conductance data. The determination of Gp thus improved the accuracy of the left ventricular dimension estimate. These results add further evidence for the possibility of continuous monitoring of left ventricular dimension by means of a conductance catheter, and demonstrate the feasibility of such studies on small experimental animals.

Animals↗
PubMed1990

[Factors influencing left ventricular function in arterial hypertension].

Using digitized M-mode echograms we evaluated the role of preload, afterload, inotropic state and left ventricular (LV) mass on LV systolic and diastolic function in 2 groups of hypertensive patients: Group 1: 25 subjects (18 men, mean age 48 +/- 6 years) with normal LV mass (less than 230 g); Group 2: 25 subjects (20 men, mean age 50 +/- 8 years) with LV hypertrophy (wall hypertrophy with normal LV diameter). As control group, we evaluated 50 normal subjects, matched for age, sex and body surface area with hypertensives. LV mass was significantly (p less than 0.001) higher as respect to normals also in hypertensives with normal LV mass; indexes of LV systolic and diastolic function were similar in normals and in hypertensives with normal LV mass and significantly lower in subjects with LV hypertrophy. The end-systolic wall stress was not significantly different in the 2 groups of hypertensives. We evaluated the relative role of preload (end-diastolic LV diameter), afterload (end-systolic wall stress) inotropic state (systolic arterial pressure/end-systolic LV diameter) and LV mass on LV systolic and diastolic function using multiple regression analysis. As regards LV systolic function, the major determinant was the systolic pressure/end-systolic diameter ratio in normals, the end-systolic stress in hypertensives. As regards LV diastolic function, the major determinant was end-systolic stress in normals and hypertensives with normal LV mass, LV mass in hypertensives with myocardial hypertrophy. Preload seems not to influence LV function in normals and in hypertensives with normal LV diastolic diameter. The major determinant of LV systolic function is the inotropic state in normals and the afterload in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

On the role of mitochondria in cell injury caused by vanadate-induced Ca2+ overload.

Incubation of isolated rat hepatocytes with vanadate (0.25, 0.5 and 1 mM) resulted in progressive accumulation of Ca2+ in the intracellular compartments. Vanadate- induced Ca2+ accumulation was related to inhibition of the plasma membrane Ca2+-extruding system, but did not involve either enhanced plasma membrane permeability to Ca2+ or the enhanced operation of a putative Na+/Ca2+ exchanger. After an initial rise in the cytosolic free Ca2+ concentration, as revealed by phosphorylase activation, Ca2+ was sequestered predominantly by the mitochondria with little contribution from the endoplasmic reticulum. As the amount of Ca2+ in the mitochondria increased, a progressive decrease in mitochondrial membrane potential occurred, together with an impairment of the ability of these organelles to further sequester Ca2+. Associated with this, there was a decrease in intracellular ATP level, formation of surface blebs and cytotoxicity. Addition of an uncoupler to vanadate-treated hepatocytes dramatically accelerated the appearance of plasma membrane blebs and toxicity. Our results demonstrate that under conditions in which the plasma membrane Ca2+ pump is inhibited, mitochondria play an important role in protecting hepatocytes against damage induced by Ca2+ overload.

Adenosine Triphosphate↗
PubMed1989

Acute haemodynamic effects of ibopamine and dopamine on isovolumic relaxation.

The effects of intraduodenal ibopamine (a new orally active inotropic agent claimed to have haemodynamic effects similar to dopamine) on isovolumic relaxation were monitored for 90 min in eight closed-chest anaesthetized dogs. Dopamine and epinine (ibopamine active metabolite) were also infused at graded doses. After 15 min, ibopamine (12 mg/kg) shortened the time constant of isovolumic relaxation, and increased stroke volume and mean aortic pressure. Peak positive dP/dt increased significantly only 10 min later. Heart rate did not change. Dopamine (10 micrograms/kg per min) similarly reduced the time constant, and increased stroke volume, mean aortic pressure, peak positive dP/dt and heart rate. Epinine (10 micrograms/kg per min) caused similar changes in peak positive dP/dt, stroke volume, mean aortic pressure, and accelerated time constant without raising the heart rate. Ibopamine and epinine therefore significantly improved the isovolumic relaxation phase, like dopamine, without however affecting the heart rate.

Animals↗
PubMed1989

Effect of enalapril on left ventricular mass and performance in essential hypertension.

The effect of enalapril on left ventricular (LV) morphology and function was studied in 12 hypertensive patients. The subjects were evaluated after 2 weeks of placebo and after 4 months of treatment with enalapril (20 or 40 mg once daily), using M-mode digitized echocardiograms. The drug reduced arterial blood pressure in all patients. Systemic vascular resistance decreased significantly without changes in cardiac output and heart rate. No patient had significant side effects. After treatment LV mass decreased significantly (233 +/- 46 to 204 +/- 37 g, p less than 0.01); the reduction was due to a decrease in septal and posterior wall thickness, without changes in LV diameter. LV systolic function remained unchanged, whereas peak lengthening rate of LV dimension, an index of LV diastolic function, increased significantly (4.05 +/- 1.8 to 5.11 +/- 1.8 s-1, p less than 0.01). After treatment the basal inverse correlation between peak shortening rate and wall stress did not change, the inverse correlation between peak lengthening rate and wall stress became closer and the basal inverse correlation between peak lengthening rate and LV mass disappeared. In conclusion, antihypertensive treatment with enalapril led to a significant regression of LV hypertrophy associated with improvement in LV diastolic performance and no deterioration of LV systolic function.

Adult↗
PubMed1989

Relationship between phasic changes in human skin blood flow and autonomic tone.

Heart rate beat-to-beat oscillations synchronous with respiration and blood pressure waves, have been found to be a marker of sympathovagal interaction in man and animals. Oscillations of heart rate, respiration, and cutaneous blood flow were simultaneously recorded to assess the relationship between autonomic nervous control and cutaneous circulation in a group of 21 healthy subjects and in a group of 6 healthy patients after brachial plexus anesthesia and consequent sympathetic blockade. In the first group, changes in posture were employed to modify autonomic tone. Relative changes in cutaneous blood flow were recorded by laser-Doppler flowmetry. Spectral analysis techniques (cross-correlation) were used to quantify the relationship between oscillations common to the recorded signals. A standing maneuver induced a significant decrease of the cross-correlation between respiratory and heart rate fluctuations (from 4.93 +/- 0.16 to 4.44 +/- 0.16 a.u.; P less than 0.001), and a significant increase of the cross-correlation between heart rate and skin blood flow fluctuations (from 0.64 +/- 0.31 to 1.33 +/- 0.21 a.u.; P less than 0.001), but did not modify the cross-correlation between respiratory and skin blood flow fluctuations (from 2.87 +/- 0.15 to 3.04 +/- 0.14 a.u.; NS). After the standing maneuver the maximum correlation between heart rate and skin blood flow was always due to oscillations in the range of 0.1 Hz (or 10-sec period), similar to the oscillations described in large arteries. Sympathetic blockade reduced significantly the cross-correlation between heart rate and skin blood flow (P less than 0.001). These results suggest that the cross-correlation between skin blood flow and heart rate at 10-sec period fluctuations can be used as an index of the influence of the autonomic tone on skin blood circulation.

Adolescent↗
PubMed1989

Cardiac autonomic dysfunction in obese subjects.

1. The prevalence of cardiac autonomic alterations was evaluated in 23 obese subjects with body mass index 37.2 +/- 3.03 kg/m2 (mean +/- SD), compared with 78 controls with body mass index 22.5 +/- 2.6 kg/m2 (P less than 0.001). 2. Cardiac autonomic function was assessed by four standard tests (heart rate response to deep breathing and to the Valsalva manoeuvre, systolic blood pressure fall after standing and diastolic pressure rise during handgrip) and by the cross-correlation test, a new method of computerized analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signal. 3. Considering tests indicative of parasympathetic function, only the heart rate response to the deep breathing and the cross-correlation test were significantly lower in the obese than in the control group [deep breathing = 13.95 +/- 8.65 beats/min (mean +/- SD) vs 24.5 +/- 7.65, P less than 0.001; cross-correlation 4.28 +/- 0.74 units vs 5.14 +/- 0.63, P less than 0.001]. Deep breathing and/or cross-correlation were abnormal in 10 (43.5%) obese subjects (deep breathing: seven subjects, cross-correlation: eight subjects). No significant difference between groups was found for the response to the Valsalva manoeuvre: the Valsalva ratio was 1.69 +/- 0.45 in obese subjects and 1.88 +/- 0.33 in controls (P = NS). The Valsalva ratio was abnormal in three obese subjects. 4. No significant differences were found between groups for tests indicative of sympathetic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Cross correlation of heart rate and respiration versus deep breathing. Assessment of new test of cardiac autonomic function in diabetes.

Cross correlation is a mathematical function whereby spectral analysis is used to describe the relationship between heart-rate fluctuations (256 R-R intervals) and respiration (simultaneously obtained by pneumotacograph). To assess its usefulness for testing autonomic integrity, cross correlation and deep breathing were compared in 141 diabetic subjects (aged 39 +/- 14 yr) and in 77 control subjects (aged 33 +/- 13 yr). To characterize patients, Valsalva maneuver, 30:15 ratio, tilt, and handgrip tests were performed in 96 of these patients; 23 had two or more abnormal tests (group A), 28 had one (group B), and 45 had none (group C). Sensitivity to parasympathetic withdrawal was compared in 9 control subjects (aged 26 +/- 4 yr) by four sequential 0.01-mg/kg i.v. atropine administrations. Reproducibility was compared in 11 control subjects (aged 25 +/- 2 yr) by repeating the tests four times for 2 consecutive days. Considering all 141 patients, cross correlation and deep breathing were less than 2SD of the mean of control subjects in 64 and 36 subjects, respectively. Considering patients who also performed other tests of autonomic function, cross correlation and deep breathing were less than 2SD of the mean of controls in 42 and 30 subjects, respectively (group A, 20 and 15; group B, 12 and 9; group C, 10 and 6). Cross correlation had better reproducibility than deep breathing (C.V. 10.3 vs. 30.6% at 6 breaths/min) and greater sensitivity to atropine (after the 1st injection, cross correlation and deep breathing decreased to 34.6 and 48.2% of baseline values, respectively; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Menadione-induced bleb formation in hepatocytes is associated with the oxidation of thiol groups in actin.

Incubation of isolated rat hepatocytes with menadione (2-methyl-1,4-naphthoquinone) or the thiol oxidant, diamide (azodicarboxylic acid bis(dimethylamide)), resulted in the appearance of numerous plasma membrane protrusions (blebs) preceding cell death. Analysis of the Triton X-100-insoluble fraction (cytoskeleton) extracted from treated cells revealed a dose- and time-dependent increase in the amount of cytoskeletal protein and a concomitant loss of protein thiols. These changes were associated with the disappearance of actin and formation of large-molecular-weight aggregates, when the cytoskeletal proteins were analyzed by polyacrylamide gel electrophoresis under nonreducing conditions. However, if the cytoskeletal proteins were treated with the thiol reductants, dithiothreitol or beta-mercaptoethanol, no changes in the relative abundance of actin or formation of large-molecular-weight aggregates were detected in the cytoskeletal preparations from treated cells. Moreover, addition of dithiothreitol to menadione- or diamide-treated hepatocytes protected the cells from both the appearance of surface blebs and the occurrence of alterations in cytoskeletal protein composition. Our findings show that oxidative stress induced by the metabolism of menadione in isolated hepatocytes causes cytoskeletal abnormalities, of which protein thiol oxidation seems to be intimately related to the appearance of surface blebs.

Animals↗
PubMed1988

Evaluation of the dilator capacity of skin blood vessels of hypertensive patients by laser Doppler flowmetry.

Knowledge of regional circulation in the skin of hypertensive patients is largely incomplete. We examined the vasodilator capacity of skin blood vessels in the foot in 20 hypertensives and in 20 age- and sex-matched normal control subjects. Vasodilator capacity was assessed by measuring skin blood flow (laser doppler flowmetry) and cutaneous vascular resistance at rest and at the peak of the postocclusive reactive hyperemia response. Skin blood flow was higher in hypertensive patients than in controls at rest (69.4 +/- 23.6 vs. 44.2 +/- 17.5 mV; P less than 0.003), but did not differ significantly after reactive hyperemia (89.2 +/- 23.5 vs 88.2 +/- 25.4 mV; N.S.). Calculated cutaneous vascular resistance was higher in controls at rest (2.99 +/- 1.06 vs 2.22 +/- 0.81 a.u.; P less than 0.3), but lower after reactive hyperemia (1.43 +/- 0.44 vs 1.64 +/- 0.43 a.u.; N.S.). Laser Doppler flowmetry is a technique suitable for studying the alterations in cutaneous microcirculation induced by hypertension. These data are compatible with structural changes in the vascular wall of hypertensive patients.

Adult↗
PubMed1988

Relationship between fluctuations in heart rate and asymptomatic nocturnal ischaemia.

In order to quantify autonomic changes related to asymptomatic nocturnal myocardial ischaemia, we analyzed heart rate fluctuations recorded during Holter monitoring in 9 subjects with coronary heart disease (21 episodes) and in 11 age-matched controls. R-R interval spectral analysis was computed in sequences of 256 heart beats, taken during the ischaemic episode, 4, 8 and 60 minutes before, and 4 and 60 minutes after. Mean heart rate, R-R interval variability (assessed by R-R interval standard deviation), low and high (respiration-linked) frequency components of R-R interval spectrum were evaluated. Mean heart rate and R-R interval variability increased only during ischaemia (from 62.9 to 73.3 beats/minute, P less than 0.02, and from 39 to 88 msec, P less than 0.01, respectively). While high-frequency components of heart rate variability remained unchanged, low-frequency peak increased during ischaemia (from 9.4 to 43.3 sec2 X 10(-3)/Hz, P less than 0.01) and also 8 minutes (P less than 0.05) and 4 minutes before (P less than 0.05). Despite a moderate increase of heart rate occurring only during ischaemia, the early rearrangement of heart rate fluctuations suggests the occurrence of changes of autonomic tone before the electrocardiographic onset of ischaemia. Due to its limited amount, this phenomenon appears to be a consequence, most likely unspecific, of factors responsible for the genesis of myocardial ischaemia.

Aged↗
PubMed1988

Load dependence of isovolumic relaxation in intact heart: facts or artifacts?

In order to study the dependence of left ventricular isovolumic relaxation on preload, afterload, and contractility the effects of infusions of dextran, phenylephrine, and dobutamine were assessed in 10 closed chest anaesthetised dogs. Left ventricular and aortic pressures and left ventricular transverse diameters were measured by micromanometers and a tracking sonomicrometer. Isovolumic relaxation time constant was computed by two different single exponential models: the first (time constant Tw) assumed the horizontal asymptote as equal to zero, whereas the second (time constant Tl) assumed a variable asymptote (Pb). To compare the two models, deviations between observed and predicted left ventricular pressures during isovolumic relaxation were computed for both (average squared difference ARSSQw and ARSSQl respectively). Dextran infusion, although increasing preload indexes, did not affect Tl (from 35.1(2.6) to 38.5(2.2) ms, NS) (mean(SEM], but increased Tw (from 28.4(1.4) to 43.8(2.1) ms, p less than 0.001); Pb was significantly shifted upwards (from -7.9(2.4) to +8.2(2.8) mmHg, p less than 0.01). Pb correlated with left ventricular end diastolic pressure (r = 0.71, p less than 0.001). Phenylephrine infusion did not change the isovolumic relaxation time course (Tl from 36.4(3.5) to 46.2(6.1) ms, NS; Tw from 26.8(2.3) to 30.5(2.9) ms, NS) nor Pb (from -9.5(2.3) to -18.7(2.3) mmHg, NS). Dobutamine infusion reduced Tl significantly (from 35.2(3.7) to 25.3(2) ms, p less than 0.02), but did not change Tw (from 27.5(2.4) to 23.3(3.3) ms, NS) nor Pb (from -7.3(1.8) to -8.8(2.3) mmHg, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Functional anatomy of the left ventricle in hypertensive subjects. Correlations with the clinical severity of hypertension].

Using computerized M-mode echocardiography we have investigated 58 hypertensive subjects in order to assess whether a correlation could be demonstrated between left ventricular changes induced by hypertension and age of the patients, the duration and severity of hypertension, and damage to other target organs. Various morphological changes of the left ventricle were detected: 14 patients (24%) had concentric hypertrophy of the left ventricle, 12 (20%) had asymmetric septal hypertrophy, 5 (8%) had dilated left ventricle without hypertrophy. Left ventricular mass was increased, when compared to normal controls in 24 patients (41%). With respect to functional abnormalities, the peak lengthening rate of left ventricular dimension in diastole was decreased (+dD/dt less than s-1) in 25 patients (43%). Eight of these patients (14%) also had depressed peak shortening rate of left ventricular diameter in systole (-dD/dt less than 1.9 s-1). Hypertensive retinopathy was present in 23 patients (39%) and impairment of renal function in 8 (14%). Left ventricular mass and systolic and diastolic parameters of left ventricular function did not correlate significantly either with the age of the patients, or with the duration and severity of hypertension, or with the damage present in target organs other than the heart. Left ventricular mass was inversely correlated with the index of left ventricular relaxation (r = -0.53; P less than 0.001), whereas neither the latter nor left ventricular mass were correlated with peak systolic stress. Instead, peak systolic stress was inversely correlated with peak shortening rate of left ventricular diameter, an index of systolic function (r = -0.50; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗