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Biomedical subjects

C Manca

Publications and source records attributed to C Manca.

At least 19 recordsLinked to original sources

Effects of acute K-strophantidin administration on left ventricular relaxation and filling phase in coronary artery disease.

In 10 patients with coronary artery disease, preserved left ventricular (LV) performance and absence of previous myocardial infarction, the effects of an acute intravenous administration of k-strophantidin (0.005 mg/kg over 10 minutes) on selected parameters of both LV systolic and diastolic function, including relaxation, were evaluated. An increase in positive first derivative of LV pressure (dP/dt) and in the ratio between dP/dt and the pressure developed (dP/dt/P) (1,530 +/- 287) 1,600 +/- 329 mm Hg/s [p less than 0.05], and 30 +/- 6 to 34 +/- 8 s-1 [p less than 0.05], respectively) demonstrated the inotropic effect of k-strophantidin, whereas volumetric parameters of systolic function (end-systolic and stroke volume indexes, and ejection fraction) did not show any significant change. However, LV relaxation was impaired by k-strophantidin injection; in fact, mean values of T constant were significantly increased from 50 +/- 12 to 55 +/- 13 ms (p less than 0.01). Lowest LV and end-diastolic pressures increased from 8 +/- 4 to 11 +/- 4 mm Hg (p less than 0.05) and from 17 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05), respectively. The end-diastolic volume and maximal rate of volumetric increase during the early and late filling phases were not modified by k-strophantidin. Mean aortic pressure increased from 110 +/- 10 to 120 +/- 12 mm Hg (p less than 0.001). Therefore, in patients with coronary artery disease and LV preserved performance, an acute intravenous administration of k-strophantidin appears to stimulate contractility and to worsen relaxation, and minimal LV and end-diastolic pressures.

Aged

Digitalis and heart failure: does digitalis really produce beneficial effects through a positive inotropic action?

Although digitalis was introduced to medicine long ago, the drug is still extensively used in clinical practice today. Opinions on its mechanism of action have undergone much change in the course of time, and the way in which cardiovascular effects are produced is still not completely clear. Limitations and contraindications for the use of digitalis substances are reported, especially in the treatment of ischemic heart disease. Preliminary data regarding the effects of digitalis on the diastolic phase are unfavorable, although the relationship between digitalis and diastolic function ought to be studied in greater depth in various clinical conditions. In spite of many recent trials, the old question of the usefulness of digitalis in the chronic treatment of patients in sinus rhythm and heart failure is still debated. An important clinical benefit in the chronic use of digitalis appears restricted to a relatively small proportion of patients with severe congestive heart failure, while in the majority of chronically treated subjects the effects of the drug are scanty or insignificant. The beneficial effect of digitalis used chronically is essentially believed to be due to its positive inotropic action. Since the vagomimetic and the antiadrenergic effects of digitalis have been demonstrated to be independent from its inotropic action, they could be considered determinants of the clinical benefits of digitalis. These indirect effects may be useful in the control of the negative neuroendocrine response developing during congestive heart failure. Thus the statement that digitalis is essentially an inotropic agent seems restrictive; its definition should reflect the favorable effects obtained in some cases of congestive heart failure rather than its various and contrasting underlying mechanisms of action.

Contraindications

Multivariate analysis of the variables affecting left ventricular filling in normal subjects.

Pulsed Doppler measurements of left ventricular filling (LVF), two-dimensional and M-mode echocardiograms were performed in 189 healthy subjects, in order to evaluate factors influencing LVF Doppler indexes in normal subjects. LVF Doppler indexes (peak E, peak A, peak E/peak A, deceleration rate of peak E (ED) were related by univariate and multivariate analyses with the following parameters: age, sex, heart rate, systolic and diastolic blood pressure, aortic root and left atrial dimensions, left ventricular mass index, left ventricular shortening fraction. The stepwise analysis showed that age by itself explained up to 18% of peak E variance, 50% of peak A variance, 61% of peak E/peak A variance and 25% of ED variance. The other variables entered into the regression, slightly improved the predictive power (less than 10%). In conclusion, age is the major independent factor affecting LVF in normal subjects, although other variables show significant correlation also after age adjustment.

Age Factors

Phenotypic variation of surface antigenic determinants in Trichomonas vaginalis detected by monoclonal antibodies.

We produced a large panel of murine monoclonal antibodies against surface determinants of Trichomonas vaginalis using the hybridoma technique. An immunoenzymatic technique (E.L.I.S.A.) was used to screen positive hybrid cells producing specific antibodies against the protozoan surface. Eleven monoclonal antibodies (Mabs) out of seventy-seven positives were further characterized. We tested antibody reactivity in order to investigate the antigenic variance among 13 different strains of Trichomonas vaginalis of different geographic origin. To elucidate the complexity of antigenic expression in Trichomonas vaginalis, further characterization of the antigenic pattern in our 13 clinical isolates was carried out by immunoblotting techniques. We demonstrate that some monoclonal antibodies react with antigens varying in molecular weight in the different strains tested. We also demonstrate the pivotal role of protozoan proteases in antigenic rearrangement.

Animals

Different effects of acute intravenous administration of k-strophanthidin and prenalterol on the diastolic phase of left ventricular function in patients with coronary arterial disease.

In 21 patients with coronary arterial disease, and with maintained (or mildly depressed) systolic function, we studied the effects of two well-known inotropic agents, namely prenalterol and k-strophanthidin, on the diastolic phase. Selected variables of both systolic and diastolic function were assessed at controlled heart rate by cardiac catheterization and left ventriculography before and after acute intravenous administration of the beta 1 agonist prenalterol (35 micrograms/kg for 3 min) and of k-strophanthidin (0.008 mg/kg for 5-10 min). Ten patients received prenalterol, and 11 patients were injected with k-strophanthidin. Administration of prenalterol induced a remarkable diminution of end-systolic volume index (mean values from 41.8 +/- 11.9 to 32.2 +/- 10.4), while k-strophanthidin showed only a tendency towards a decrease (mean values from 43.4 +/- 13.2 to 40.7 +/- 15.1). After k-strophanthidin, we did not observe any significant changes in the peaks of maximal rate in volumetric increase during filling phase whereas, after prenalterol, a noteworthy increase of the first peak was accompanied by a significant decrease of the second peak. The lowest and end filling left ventricular pressures were decreased by prenalterol (mean values from -0.8 +/- 0.1 to -2 +/- 0.5 and from 10.6 +/- 4.6 to 4.1 +/- 1.1 respectively), whereas k-strophanthidin increased left ventricular end diastolic pressure (mean values from 11.6 +/- 4.3 to 17.1 +/- 9.1). Prenalterol induced a relevant increase of ejection fraction (mean values from 0.52 +/- 0.1 to 0.61 +/- 0.008), whereas k-strophanthidin produced only a nearly significant (P less than 0.06) mild increase (mean values from 0.51 +/- 0.06 to 0.54 +/- 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Tamoxifen binding sites heterogeneity in breast cancer: a comparative study with steroid hormone receptors.

Steroid receptors and tamoxifen binding sites (TBS) were assayed in the soluble fraction of 121 primary breast cancers. Scatchard analysis of TBS in high speed supernatant (100,000 g) showed one population of binding sites; however, biphasic plots were obtained in low speed supernatants (40,000 g). Isoelectric focussing of supernatants preincubated with radioactive tamoxifen identified two classes of TBS (pI 4.1-4.6) which have different binding affinities and bind neither oestradiol nor diethylstilbestrol. Association between TBS and steroid receptors was: TBS positive/progesterone receptor positive 32.6%, TBS positive/glucocorticoid receptor positive 52.7%, TBS positive/oestrogen receptor positive 60% and TBS positive/androgen receptor positive 72.2%. We conclude that heterogeneous TBS are present in low speed fractions and can be easily separated from the oestrogen receptor by isoelectric focussing. The association between TBS and steroid receptor status could be of clinical value in the management of primary breast cancer.

Breast Neoplasms

Different effects of captopril and other angiotensin converting enzyme inhibitors on cardiovascular preparations.

The effects of captopril and of other angiotensin-converting enzyme inhibitors (zofenopril, fosenopril and enalaprilic acid) were tested on the isolated rabbit heart and aorta. Captopril elicited an erratic negative inotropic effect and a reduction in basal coronary perfusion pressure (10(-5)-10(-4) M). The increase of coronary perfusion pressure induced by vasopressin, methoxamine, angiotensin II and Bay K 8644 was partially antagonized by captopril (10(-7)-10(-4) M) in a non-specific manner. These actions were not modified by saralasin or indomethacin and by ex vivo pretreatment with captopril itself. On the aortic strips, the contraction plateau induced by KCl and angiotensin II was partially inhibited (10(-6)-10(-4) M), while no effect was observed on those induced by noradrenaline, serotonin and PGF2 alpha. The Ca2+ concentration-response curve appeared shifted to the right in a non-competitive manner. The other angiotensin-converting enzyme inhibitors showed no effect up to 10(-4) M on isolated heart or aorta. Results obtained with captopril were consistent with vasorelaxant activity independent of the tissue renin-angiotensin system. Modulatory activity on the intracellular calcium movement may be involved.

Angiotensin-Converting Enzyme Inhibitors

Diagnosis of an aorto-caval fistula by echo 2D color Doppler flow imaging and echocardiographic probe.

We describe a clinical case presenting two unusual features. The first was a spontaneous aorto-caval fistula which had developed from rupture of an atherosclerotic aortic aneurysm into the inferior vena cava. The second uncommon feature depended on the unusual method by which the diagnosis was performed. In fact, using an echo-Doppler color flow (HP 77020A ultrasound system) with a 2.5 MHz echocardiographic probe abdominal examination revealed an aneurysm of the abdominal aorta that communicated with a dilated inferior vena cava. Furthermore, flow study with pulsed color Doppler revealed a continuous turbolent, mixed (arterial and venous) blood flow into the vena cava.

Aorta, Abdominal

[Effects of amrinone on isolated heart preparations: comparative study with other inotropic agents].

We compared the effects of the phosphodiesterase inhibitor amrinone, the beta-adrenergic partial agonist xamoterol and the digitalis glycoside, ouabain, on isolated rabbit hearts perfused with the Langendorff technique. Heart rate, left ventricular pressure, as an index of myocardial contractility and coronary perfusion pressure, as an index of coronary resistances, were assessed before and after each drug. Perfusion with concentrations of each agent varying from 10(-9) to 10(-4) M induced a dose-dependent increase of left ventricular systolic pressure averaging 32.5 +/- 1.5% after amrinone (10(-5) M), 46.2 +/- 0.5% after xamoterol (10(-5) M) and 19.0 +/- 2.1% after ouabain (10(-4) M). Among the 3 agents, only amrinone was able to reduce basal coronary perfusion pressure (18.4 +/- 1.2% at the dose of 10(-5) M) and inhibit vasopressin-induced coronary spasm (86.8 +/- 2.5% inhibition at 10(-5) M); no significant change of coronary perfusion pressure was noted with either xamoterol or ouabain. Heart rate was not significantly modified by amrinone whereas, at the doses of 10(-5)-10(-4) M, xamoterol increased it by 21.6 +/- 0.7% and ouabain reduced it by 12.3 +/- 1.1%. Our results show that amrinone, in comparison with digitalis glycosides and beta-adrenergic agonists, presents the unique property to increase myocardial contractility with concomitant coronary vasodilation without significant changes of heart rate. Ouabain has a less potent positive inotropic activity and a slight negative chronotropic action, whereas xamoterol inotropic effect is accompanied by an increase of heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists

[The diagnosis by a Doppler color echocardiographic method of an aortocaval fistula following the rupture of an aortic aneurysm into the inferior vena cava].

We describe a clinical case presenting 2 rare features. The first was a spontaneous aortocaval fistula which had developed from rupture of an atherosclerotic aortic aneurysm into the inferior vena cava. The second infrequent feature depended on the unusual method by which the diagnosis was performed. In fact, using an echo-color Doppler flow imaging (HP 77020A ultrasound system) with a 2.5 MHz echocardiographic probe abdominal examination showed an aneurysm of the descending aorta that communicated to a dilated inferior vena cava. Furthermore, flow study with color Doppler showed a continuous turbulent, mixed (arterial and venous) blood flow into the inferior vena cava.

Aortic Aneurysm

Diagnostic features of body surface potential maps in patients with myocardial ischemia and normal resting 12-lead electrocardiograms.

Body surface maps recorded from 35 ischemic patients with normal resting 12-lead electrocardiograms were compared with those obtained from 36 age- and sex-matched normal subjects. From instantaneous maps of each subject 187 variables were derived relating to the configuration (80 variables) and magnitude (104 variables) of the potential distribution and duration of the electrocardiographic intervals (3 variables). By using stepwise discriminant analysis we selected 3 variables whose linear combination enabled us to correctly allocate 91% of the study population (jacknife procedure; specificity 92%, sensitivity 91%). To substantiate the validity of the results the discriminant function was tested on a new independent population consisting of 27 ischemic patients and 54 normal subjects from another laboratory. A proper allocation was obtained in 86% of the cases (specificity 87%, sensitivity 85%). The large number of correctly classified ischemic patients and the repeatability of the results indicate that the adopted criteria are good markers of ischemic heart disease.

Adult

Dynamic left-ventricular tract outflow obstruction: a late complication of mitral valve replacement.

The case presented is a 47-year-old woman with left-ventricular outflow tract obstruction which was the late complication of mitral valve replacement (4 years later). The diagnosis was made using two-dimensional Doppler echocardiography (echo-2D Doppler) and confirmed by cardiac catheterization. Protrusion of the prosthetic ring towards the intraventricular septum reducing the diameter of the outflow tract to 7-8 mm and creating a dynamic obstruction (30 mm Hg on cardiac catheterization, and 44 and 75 mm Hg on echo-2D Doppler basally and after isoamyl nitrite inhalation, respectively) was recorded. The echo-2D Doppler technique appears to be useful in detecting this postsurgical mitral complication.

Echocardiography, Doppler

[Effects of chronic administration of nifedipine on echo-Doppler parameters of left ventricular filling in hypertensive patients].

This study aimed determining the chronic effects of nifedipine (N) on left ventricular filling in 25 patients (mean age 55) with mild to moderate arterial hypertension. M-mode, B-mode and pulsed Doppler measurements were performed at baseline, after 30 min from administration of sublingual N (10 mg) and after 6 months of therapy with slow release N (max dose: 60 mg die). Acute and chronic N reduced significantly both systolic (p less than 0.001) and diastolic pressure (p less than 0.001). At the end of the treatment with slow release N, and septal wall thicknesses had a slight but significant decrease (p less than 0.01). Diastolic and systolic dimension were not modified. Left ventricular mass index decreased significantly from 141 +/- 34 to 130 +/- 31 g/m2 (p less than 0.05). The Doppler-derived diastolic filling indexes (peak E, ratio peak E/A,E deceleration) were abnormal at baseline, and had a significant increase after sublingual and chronic therapy. Changes in left ventricular mass index and diastolic filling indexes were not correlated. A significant correlation was found between peak E changes after acute and chronic N administration (r = 0.732 and p less than 0.001). The results of this study demonstrate that both acute and chronic administration of N modify transmitral flow velocity pattern, suggesting that, in hypertensive patients, left ventricular filling abnormalities are partly dynamic and reversible. Our findings also demonstrate that acute N effects may predict the chronic results.

Adult

[Effects of i.v. nicardipine in the treatment of hypertensive crisis].

The availability of i.v. nicardipine has urged us to prove this drug in the treatment of hypertensive attacks (SAP greater than or equal to 210 mmHg and/or DAP greater than or equal to 110 mmHg). Two groups of patients (each made up of ten subjects) were treated with 2 mg and 5 mg respectively of i.v. nicardipine injected for 4 min while mean systolic and diastolic arterial pressure and heart rate were registered until three hours. I.V. nicardipine administration induced in both groups of patients a decrease in systolic pressure from 20 to 30% while diastolic arterial pressure decreased from 15 to 18% in the first group and from 20 to 25% in the second one. Heart rate showed an initial mild increase following arterial vasodilator action of nicardipine whereas it decreased significantly from 120 min in the presence of an unchanged hypotensive effect of the drug. One patient did not respond to nicardipine while another felt chest pain and palpitations. In conclusion our results are satisfactory and argue for the inclusion of nicardipine among the drugs that may be considered useful for the treatment of hypertensive attacks.

Acute Disease

Comparison of five different stress testing methods in the ECG diagnosis of coronary artery disease. Correlation with coronary arteriography.

Five different stress testing methods: bicycle ergometer exercise (BE), treadmill exercise (TD), isoproterenol infusion test (IPN), dopamine infusion test (DPM), and atrial pacing (AP), were performed on 90 male patients who underwent coronary arteriography. Ischemic S-T segment depression of 1.0 mm or greater was used as the criterion for a positive test. Within the group of 56 subjects having significant coronary artery disease (CAD) the diagnostic sensitivity of the single tests was as follows: 64.3% for BE, 66.1% for TD, 69.6% for IPN, 41.1% for DPM, 75.0% for AP. For the 34 subjects with no CAD the folowing specificity was found: 88.2% for BE and for TD, 82.3% for IPN, 85.3% for DPM, 63.8% for AP. When the results of the different tests were combined, it was seen that the association of an ergometric test with IPN enhanced the sensitivity of the exercise test (p less than 0.05) without significantly decreasing the specificity.

Adult