Biomedical subjects

G Finardi

Publications and source records attributed to G Finardi.

At least 55 records · Page 3Linked to original sources

PubMed1993

Determinants of left ventricular function before and after regression of myocardial hypertrophy in hypertension.

Using digitized M-mode echocardiograms, we evaluated the determinants of left ventricular (LV) systolic and diastolic function in 30 hypertensives with LV hypertrophy (LV mass > 230 g and normal LV diastolic diameter), before (LV mass 319 +/- 26 g) and after normalization of LV mass (196 +/- 21 g) by antihypertensive treatment with angiotensin converting enzyme inhibitors. As a control group we selected 50 normal subjects. Using multiple regression analysis we studied the relative role of preload (LV end-diastolic diameter), afterload (end-systolic wall stress), inotropic state (systolic pressure/end-systolic LV diameter ratio), and LV mass on LV systolic (peak shortening rate of LV diameter) and diastolic function (peak lengthening rate of LV diameter). The major determinant of systolic function was the end-systolic stress in hypertensives before treatment and the systolic pressure/end-systolic LV diameter ratio in normals and in hypertensives after treatment. The major determinant of diastolic function was LV mass in hypertensives before treatment and end-systolic stress in normals and in hypertensives after normalization of LV mass by treatment. Preload seems not to influence LV function in normals and in hypertensives with normal LV diameter. The inotropic state is the major determinant of systolic function in normals and in hypertensives after treatment, whereas this role is played by afterload in hypertensives before treatment. The diastolic function is primarily influenced by after-load in normals and in hypertensives after regression of myocardial hypertrophy, whereas in hypertensives with myocardial hypertrophy LV mass is the major determinant of diastolic function.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Low-density lipoprotein oxidation in essential hypertension.

OBJECTIVES: To investigate the occurrence of enhanced low-density lipoprotein (LDL) oxidation as an additional factor promoting atherosclerosis progression in hypertensive patients. DESIGN: The oxidation of plasma LDL was investigated in a group of untreated patients with mild-to-moderate essential hypertension without clinically evident target organ damage and in a group of control subjects. METHODS: LDL oxidation was evaluated as both the susceptibility to oxidation in vitro and the presence of plasma anti-oxidized LDL antibodies (as an index for oxidation in vivo). RESULTS: LDL from hypertensive subjects exhibited enhanced susceptibility to oxidation in vitro as revealed by early and accelerated generation of conjugated dienes after exposure to CuSO4. Vitamin E concentration in LDL from hypertensive subjects was slightly but significantly decreased and its efficiency in protecting LDL from oxidation was impaired. Furthermore, a higher plasma anti-oxidized LDL titre was found in hypertensive patients. Subclass analysis revealed that the contemporary presence of hypercholesterolaemia did not significantly modify either the increased susceptibility of LDL to oxidation or the presence of plasma anti-oxidized LDL antibodies detected in hypertensive patients. Moreover, no correlation was found between LDL oxidation parameters and blood pressure values. CONCLUSIONS: LDL from hypertensive patients is more susceptible to oxidation in vitro and is more promptly oxidized in vivo. These findings suggest a possible participation of LDL oxidation in promoting and accelerating the atherosclerosis that often develops in hypertensive patients.

Adult↗

PubMed1993

Specificity of autoantibodies against oxidized LDL as an additional marker for atherosclerotic risk.

BACKGROUND: LDL oxidation is a crucial step in the development and progression of atherosclerotic lesions. The detection of an increase in the anti-oxidized LDL antibody titre may thus represent a biological marker of enhanced LDL oxidation in vivo. METHODS: The occurrence of anti-oxidized LDL autoantibodies was investigated in control patients, in patients with atherosclerotic coronary artery disease, in those without clinically relevant signs of atherosclerosis, but considered at risk, and in patients with chronic alcohol-related liver disease. RESULTS: Anti-oxidized LDL autoantibodies were present in the plasma of the majority of patients with overt coronary atherosclerosis. An increased antibody titre can also be detected well before the onset of clinically relevant signs of the atherosclerotic disease in patients classically considered at risk, indicating the occurrence of in-vivo LDL oxidation during atherosclerosis development. The specificity of molecular targets (LDL) for oxidative modifications is supported by the demonstration that anti-oxidized LDL autoantibodies are absent in the plasma of alcoholic patients who exhibit a marked increase in biological markers of oxidative stress but do not classically develop atherosclerosis. CONCLUSION: These data demonstrate that the occurrence of anti-oxidized LDL autoantibodies could be specifically related to the promotion and progression of atherosclerosis and is not a simple epiphenomenon of any oxidative process occurring in vivo.

Adult↗

PubMed1993

Low-density lipoprotein oxidation and antioxidized LDL antibodies in peritoneal dialysis patients.

Due to the potential atherogenic effects of oxidized low-density lipoproteins (LDLs), LDL oxidation was studied in a group of uremic patients on chronic peritoneal dialysis. The results were compared with those obtained in a group of 70 controls, 10 uremic patients on predialytic conservative therapy, and 11 patients on repetitive hemodialysis. LDL oxidation was evaluated in all subjects as the susceptibility to in vitro oxidation (monitoring the resistance to Cu(2+)-induced formation of conjugated dienes, lag-phase minutes) and the presence of plasma antioxidized LDL antibodies, expressed as the ratio anti-ox-LDL/antinative LDL antibodies. Vitamin E (main antioxidant agent) content in LDLs was also measured and the lipid profile studied. No significant changes in vitamin E concentration were found, although LDLs from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier production of conjugated dienes and by the presence of a higher antibody ratio), as compared to control subjects. Analysis of the different groups of uremic patients revealed that peritoneal dialysis, not hemodialysis, significantly ameliorated the oxidation markers. However, prolonged treatment with peritoneal dialysis caused a decrease in vitamin E concentration in LDLs and increased their susceptibility to oxidation.

Antibodies↗

PubMed1993

[Effectiveness and tolerability of simvastatin in subjects with primary hypercholesterolemia. Multicenter study].

The efficacy and safety of simvastatin were evaluated in an open multicenter study over a 24-week period. One hundred seventy-two patients (91 men, 81 women) with primary hypercholesterolemia (mostly polygenic) were enrolled in 14 Centers in Northern Italy. The mean age was 55.8 +/- 9.7 years and the mean baseline total cholesterol level was 305 +/- 59 mg/dL. After 4 weeks on an AHA step 1 diet, patients who met the inclusion criterion (total cholesterol > or = 250 mg/dL) were given simvastatin 10 or 20 mg in the evening. The dose could be titrated up to a maximum of 40 mg o.d. at week 6 and 12. No dose titration was allowed after week 12. One hundred forty-nine patients (86.6%) completed the study according to the protocol, 2 (1.2%) were withdrawn from the study because of adverse events not related to the drug, 21 (12.2%) were unavailable for follow-up. Simvastatin treatment was associated with a sustained dose-related reduction in total and LDL cholesterol (-28% and -39% respectively at the end of the study). Triglycerides showed a significant descending trend (-16% at week 24) and HDL-C increased by 9%. Apolipoproteins were measured in only 25 patients: apo B was reduced by 30% and apo A1 increased by 9%. Clinical side effects were not relevant. Mean levels of GOT, GPT and CPK significantly increased after 6 weeks on simvastatin, but remained stable and at any rate ioitlin the normal range thereafter. Eight patients (5.4%) experienced small transaminase level elevations (< 3ULN) and six (4%) small CPK elevations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

[Vasovagal syncope].

The nature of most syncopal episodes, previously unknown, was recently elucidated by new diagnostic techniques such as the use of the tilt test. The vasovagal syncope can be clinically diagnosed by means of the tilt test. The transitory loss of consciousness during prolonged orthostasis is typically associated with sudden hypotension and bradycardia, which are commonly preceded by relative tachycardia and by premonitory symptoms such as pallor, nausea, asthenia, yawns, hyperventilation, mydriasis, humming, lasting several minutes. The nature of the vasovagal reflex is now better understood: in subjects with vasovagal syncope, during prolonged orthostasis, it was observed a fall in the venous return, inducing an increased sympathetic drive to the heart (with positive inotropic and chronotropic effect) and a lower ventricular filling. The powerful contraction around an almost empty cardiac chamber induces the activation of ventricular mechanoreceptors, and through a reflex mechanism, a sudden increase in the vagal and a sudden reduction in the sympathetic drive. These autonomic changes are responsible for a sudden hypotension and bradycardia. The discussion is still open about the origin of the reduced venous return: it probably originates from a redistribution in the blood volume, due to a venous pooling in the lower limbs or from a reduced muscle tone, because many subjects with vasovagal syncope are slender and with less developed muscle apparatus. Others suggest that a reduction in the sympathetic drive to the vessels, responsible for a progressive hypotension in the minutes preceding syncopal episodes, is the origin of the reduced venous return. In this review a diagnostic pattern for the assessment of the vasovagal syncope is suggested. The medical history, clinical examination, electro- and echocardiogram, chest x-ray identify two main groups of patients (with or without cardiopathy) who will follow different diagnostic protocols. The therapy of vasovagal syncope, which is based on beta-blockers, scopolamine, dysopiramide and plasma expanders, is reviewed.

Hemodynamics↗

PubMed1992

Left ventricular function after reversal of myocardial hypertrophy in systemic hypertension, and response to acute increase of afterload by cold pressor test.

Using digitized M-mode echocardiography, the left ventricular (LV) response to acute increase in blood pressure after regression of myocardial hypertrophy due to an effective antihypertensive treatment was evaluated. Fifteen hypertensive patients with basal LV hypertrophy (LV mass greater than 230 g, and normal LV diastolic diameter) and normal LV mass after 3 to 4 months of treatment with angiotensin-converting enzyme inhibitors were selected for study. Subjects performed a cold pressor test before and after therapy. LV systolic function was normal in all subjects. LV diastolic function (impaired at basal evaluation in 13 subjects) improved after therapy in all subjects, with normalization in 10. Before treatment, the cold pressor test induced significant increases in blood pressure and heart rate without changes in LV parameters. After regression of hypertrophy, the cold pressor test induced increases in hemodynamic parameters comparable to those of the basal test, and LV parameters remained unchanged. Our results indicate that regression of myocardial hypertrophy induced by angiotensin-converting enzyme inhibitors does not impair the ability of the left ventricle to face acute increases in afterload. The improvement in LV diastolic function (found at rest after reversal of hypertrophy) persists during the cold pressor test, which confirms that it is primarily due to LV mass reduction and is not simply a consequence of decrease in afterload induced by treatment.

Adult↗

PubMed1992

Perindopril versus captopril: efficacy and acceptability in an Italian multicenter trial.

The aim of this 3-month, double-blind, double-dummy, parallel group study was to compare the antihypertensive efficacy and acceptability of perindopril (4-8 mg/day) in 54 patients (30 males, 24 females, 25-68 years of age) and captopril (50-100 mg/day) in 54 patients (39 males, 15 females, 29-66 years of age) in the treatment of essential hypertension. In a subgroup of 38 patients a complete echocardiographic study was performed. The two groups had similar (ANOVA) blood pressure (BP), heart rate (HR), body mass index, and duration of hypertension. Supine and standing BP was significantly reduced by both drugs, without differences between them. Owing to poor control of BP, hydrochlorothiazide (25 mg/day) was added to 27% of patients on perindopril and to 41% of patients on captopril (p less than 0.05). Normalization of supine diastolic BP (less than or equal to 90 mm Hg) was obtained in 67% of patients on perindopril and in 47% of patients on captopril (p less than 0.01). No change in HR was detected. Only mild untoward effects were recorded. Left ventricular mass was significantly reduced by either drug, with no change in systolic function. In conclusion, perindopril and captopril, at these doses, were both well tolerated and on average reduced BP to a similar extent; however, treatment with perindopril showed that fewer patients needed the addition of a thiazide and BP became normal in a larger number of patients.

Adult↗

PubMed1992

Tumor necrosis factor alpha induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation.

The incubation of human mammary adenocarcinoma cells (BT-20) with tumor necrosis factor alpha in the absence or presence of cycloheximide resulted in progressive DNA fragmentation. This was preceded by a sustained increase in intracellular free Ca2+ concentration and was not detected in cells pretreated with intracellular Ca2+ chelators, calmodulin antagonists, or activators of protein kinase C. Image analysis of fura-2-loaded BT-20 cells treated with tumor necrosis factor alpha revealed that, in many cells, the initial increase in Ca2+ level occurred in a cellular region that corresponded to the localization of the nucleus. Our findings suggest that tumor necrosis factor alpha can promote an increase in intranuclear free Ca2+ which, in turn, may stimulate Ca(2+)-dependent endonuclease activity, resulting in DNA fragmentation and apoptosis.

Adenocarcinoma↗

PubMed1992

Continuous monitoring of right ventricular volume changes using a conductance catheter in the rabbit.

To assess the reliability of conductance (G) catheter for evaluating right ventricular (RV) volume changes, a miniature (3.5F) six-electrode catheter was developed and tested in 11 New Zealand rabbit hearts. In five animals the heart was excised; in six it was left in the thorax. RV conductance was recorded while the RV was filled with blood in 0.25-ml steps at different left ventricular (LV) volumes. Linear correlation of measured conductance vs. reference volumes was computed. RV conductance was highly correlated with reference volume [correlation coefficient (r) ranging from 0.991 to 0.999]. Slope of regression lines was not significantly affected by LV volume variations in 1-ml steps or by acute conductance changes of structures surrounding the heart, whereas the intercept was affected only by the 0- to 1-ml LV volume change. In four rabbits, RV conductance changes during a cardiac cycle [stroke volume- (SV) G] were compared in vivo with electromagnetic flow probe-derived estimates of SV (SVem) as stroke volume was varied by graded inferior vena caval occlusion. SV-G correlated well with SVem (r ranging from 0.92 to 0.96). This correlation persisted after the thorax was filled with saline; however, significant differences were found in individual slopes (P < 0.001). These results show that the conductance catheter has a potential to reliably monitor in vivo relative RV volume changes in small-animal hearts.

Anesthesia↗

PubMed1992

Influence of age and sex on left ventricular anatomy and function in normals.

Using digitized M-mode echograms, we evaluated the influence of sex on age-related changes of left ventricular (LV) anatomy and function in a normal population (75 males and 75 females, subdivided in age groups for each decade from 20 to 70 years). Aging is accompanied with an increase in septal and wall thickness in both males and females and in LV diameter only in males, with a progressive increase of LV mass more pronounced in males than in females. As regards LV function we found a progressive slowing of relaxation in females and of both contraction and relaxation in males, not related to changes in LV mass.

Adult↗

PubMed1992

Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.

BACKGROUND: Diabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. METHODS AND RESULTS: To assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44 +/- 2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.18-0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95 +/- 0.12 In-msec2 versus 6.73 +/- 0.11, p < 0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11 +/- 0.18 In-msec2 versus 6.52 +/- 0.14, p < 0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. CONCLUSIONS: Diabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.

Adult↗

PubMed1992

High plasma levels of catecholamines during insulin-induced hypoglycemic stress do not cause beta-adrenergic receptor sequestration.

In the present investigation insulin-induced hypoglycemia was used as a powerful stimulus to rapidly release epinephrine from the adrenal medulla. Insulin injection raised epinephrine 16-fold and doubled norepinephrine plasma levels. The aim of this attempt was to induce beta-adrenergic receptors (beta-ARs) sequestration in vivo on mononuclear leukocytes (MNLs). The number of total and surface beta-ARs was significantly increased 30 minutes after insulin administration, with only partial recovery at 90 minutes. No detectable receptor sequestration was observed: surface receptors were about 90% of total receptors in all the conditions examined. Isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) accumulation was also increased after 30 minutes (+66%) and 90 minutes (+65%) of insulin injection. Basal and forskolin-stimulated intracellular cAMP values were unchanged. We conclude that, even after a strong release of catecholamines, beta-AR redistribution cannot be demonstrated on MNLs.

Adrenal Medulla↗

PubMed1992

[The evaluation of the end-ejection pressure-length relation as an index of regional contractility].

Although end-systolic pressure-length relationship (ESPLR) is now widely used as a regional substitute for the end-systolic pressure-volume relationship, there are some reservations about its use as an index of systolic performance. This study aimed at assessing whether by using end-ejection (zero aortic flow) as a definition of end-systole, ESPLR can be used to characterize myocardial performance independent of load, and if the choice of the region where to implant the sonomicrometers is critical. Ten anaesthetized dogs (16 +/- 2 kg) were instrumented with a left ventricular (LV) pressure micromanometer and an aortic flow probe. Sonomicrometers were implanted in the apical (L1) and the mid-ventricular (L2) regions of the anterior LV wall, and in the basal region of the lateral wall (L3). End-systolic pressure-length relationships were obtained during acute preload reduction induced by the inflation of a vena caval balloon. This evaluation was repeated after increasing end-diastolic pressure to 14-18 mmHg (delta PL), after increasing systolic pressure by 15 (delta P-I) and 25 mmHg (delta P-II) with graded descending aorta occlusion, and during dobutamine infusions at 2.5 (Db 2.5) and 5 micrograms/kg/min (Db5). End-systolic pressure-length relationships (r > 0.97; pressure range: 70-100 mmHg) were characterized by their slopes (Ees), the extrapolated intercept at zero pressure (L0) and the values of segment length at a pressure of 75 (L75) and 100 mmHg (L100). In all the myocardial regions studied by sonomicrometry, the increments in preload and afterload did not significantly shift ESPLR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Noninvasive assessment of the relationship between cardiac and autonomic function in diabetes.

In order to assess a possible relationship between left ventricular (LV) function and cardiac autonomic involvement in type-1 insulin dependent diabetes, we performed M-mode echocardiograms and autonomic function tests in 21 patients (mean age +/- SD, 38 +/- 11 years, range 18-55, 16 male and 5 female). In 7 patients and in 21 age-matched controls the echocardiogram was also recorded before and during handgrip. At rest, ventricular function abnormalities were found only in 4 subjects, and no significant correlation was found between echocardiographic parameters and autonomic function tests. Unlike controls, during handgrip diabetic subjects failed to increase peak Vcf and peak filling rate, and increased their left ventricular end-systolic diameter. The changes in LV parameters during handgrip were significantly correlated with resting autonomic function tests (p less than 0.025). Our results suggest that resting cardiac function may be normal in diabetics despite high incidence of abnormal autonomic tests. Latent abnormalities of left ventricular function can be unmasked by acute haemodynamic challenges such as handgrip, and are correlated with abnormalities in autonomic function tests.

Adolescent↗

PubMed1991

Time course of pressure and flow in ascending aorta during ejection.

To analyze aortic flow and pressure relationships, 10 closed-chest anaesthetised dogs were instrumented with electromagnetic aortic flow probes and micromanometers in the left ventricle and ascending aorta. Left ventricular ejection time was divided into: time to peak flow (T1) (both pressure and flow rising), peak flow to peak pressure time (T2) (pressure rising, flow decreasing), and peak pressure to dicrotic notch time (T3) (pressure and flow both decreasing). These time intervals were expressed as percent of total ejection time. Load-active interventions rose markedly T2 (from 4.2 +/- 5.5 to 19.4 +/- 3.5 after phenylephrine (p less than 0.02); from 4.2 +/- 6.5 to 21.2 +/- 5.3 after dextran (p less than 0.02)). Conversely, dobutamine reduced T2 from 4.4 +/- 5.9 to -2.5 +/- 6.5 (p less than 0.05). Thus, during load-active interventions aortic pressure increases for a longer T2 time although forward flow is decreasing, as a result of higher aortic elastic recoil during ejection. Conversely, beta 1-adrenergic stimulation significantly shortens T2. Dynamic pressure-flow relationship is thus continuously changing during ejection. T2 seems to be inversely related to the efficiency of left ventricular ejection dynamics.

Animals↗

PubMed1991

Double-blind comparison of perindopril and captopril in hypertension. Effects on left ventricular morphology and function.

Using digitized M-mode echocardiograms, we compared, in a double-blind study, the effects of 4 to 8 mg perindopril given once daily and 25 to 50 mg captopril given twice daily on the left ventricle (LV) in 20 hypertensive patients. Both treatments significantly (P less than .001) lowered blood pressure, reducing systemic vascular resistances. After 3 months both drugs induced a comparable percentage of reduction in LV mass, with an increase in the peak rate of LV relaxation and no changes in the peak rate of LV contraction. Our results demonstrate that perindopril once daily is an effective antihypertensive agent; it is also able, like captopril, to induce regression of LV hypertrophy, with improvement in diastolic performance and no deterioration in ventricular systolic function.

Adult↗

PubMed1991

[The variability of the heart rate, arterial pressure and peripheral circulation as the indices of autonomic control in essential hypertension].

In recent years the influence of autonomic nervous system on cardiac rhythm and blood pressure has been increasingly studied by analysis of cardiovascular fluctuations, particularly in diabetic and normal persons under various physiologic conditions, while still few data exist on essential hypertension. To characterize the autonomic cardiovascular control in essential hypertension we studied 22 untreated hypertensives, diagnosed within 1 year (mean age 43 +/- 2 years, mean +/- SEM) and 16 age-matched normotensives. Recordings of RR interval, breathing activity, noninvasive blood pressure (Finapres) and skin arteriolar flow (infrared photoplethysmogram) were obtained while in supine position and after sympathetic activation induced by passive transition to upright posture (tilting table). Autoregressive power spectral analysis was then carried out, and low- (0.03-0.15 Hz, LF) and high-frequency fluctuations (0.15-0.35 Hz, HF) were measured. LF and HF have been considered as markers of sympathetic and parasympathetic activity on the heart, respectively, and as markers of sympathetic and mechanic chest activity on the circulation, respectively. In supine position both cardiac and vascular variability were similar in both hypertensive and normotensive groups. After tilting however the increase in the sympathetic component of cardiac variability was blunted in hypertensives with respect to normotensives (hypertensives LFnu from 43.6 +/- 4.7 nu to 59.4 +/- 5.1 nu, p less than 0.005; normotensives LFnu from 36.9 +/- 3.3 nu to 83.4 +/- 2.6 nu, p less than 0.001), the increase in LFnu being statistically (p less than 0.001) reduced in the hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗