Biomedical subjects
Publications and source records attributed to F Cucchini.
A prolapsing mitral valve with a double orifice ('hole type') was documented by echocardiography in a 35-year-old male. His symptoms were associated to supraventricular ectopic beats and persisted unchanged during a 3-year follow-up. This malformation is usually considered benign but, as fragmentation of the atrioventricular conduction tissue was reported in some cases, a periodic observation is advisable.
The pharmacokinetics of ajmaline were studied in 10 patients with suspected paroxysmal atrioventricular block who received a 1 mg/kg intravenous dose over 2 minutes for diagnostic purposes (ajmaline test). Plasma concentration decay followed a triexponential time course with a final half-life much longer (7.3 +/- 3.6 hours) than that previously found by other investigators (about 15 minutes). Mean total plasma clearance and renal clearance were 9.76 ml/min/kg and 0.028 ml/min/kg, respectively. Although most of the dose was eliminated through the extrarenal route (only 3.5% of the intravenous dose was recovered in urine), no fluorescent metabolites could be detected either in plasma or urine. The steady-state volume of distribution averaged 6.17 L/kg, and plasma protein binding ranged between 29 and 46%. Three patients developed a transient atrioventricular block after ajmaline administration. In the remainder, the drug prolonged atrio-His bundle (AH interval), His bundle-ventricular (HV interval) and intraventricular (QRS interval) conduction times. Corrected ventricular repolarisation time (QTc interval) showed less marked changes, which were biphasic at times. The mean maximum ajmaline-induced increase in HV interval was 98%, in QRS was 58%, in AH was 30%, and in QTc was 17%. In most cases the time course of electrocardiographic changes lagged behind that of plasma concentrations, suggesting a delayed equilibrium of plasma concentrations with the site of action (hysteresis). Despite that, the pharmacokinetic-pharmacodynamic model, which accounted for hysteresis, failed to fit the experimental data adequately.(ABSTRACT TRUNCATED AT 250 WORDS)
Pneumopericardium is a rare entity, but it can occur in a wide variety of clinical situations. The spontaneous cases are very rare and generally can be associated with some predisposing or precipitating conditions. We report a case in which the pathogenesis of pneumopericardium undefined after conventional diagnostic clinical investigation. A concise review of the recent literature is presented, and some practical clinical remarks are made.
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.
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)
In 13 patients with chronic stable angina, left ventricular pressures were measured by catheter-tip micromanometer, and left cineventriculography was performed at matched atrial paced rates before and 20 min after administration of intravenous gallopamil (3 mg). Mean plasma concentration of gallopamil at the second haemodynamic and angiographic assessment was 18.6 +/- 5.7 ng.ml-1. Left ventricular peak systolic pressure decreased from 134 +/- 12 to 125 +/- 13 mmHg (P less than 0.005) and mean aortic pressure from 94 +/- 11 to 91 +/- 9 mmHg (ns). Peak positive first derivative of left ventricular pressure (+dP/dt) and maximal velocity of the contractile element (Vcemax) significantly decreased (from 1828 +/- 334 to 1702 +/- 304 mmHg.s-1, P less than 0.002, and from 51 +/- 11 to 43 +/- 5 s-1, P less than 0.001, respectively). Left ventricular protodiastolic pressure decreased from -0.6 +/- 2.9 to -2.8 +/- 2.9 mmHg (P less than 0.005) and left ventricular end-diastolic pressure from 9.5 +/- 3.4 to 8.9 +/- 4.6 mmHg (ns). No changes occurred in peak negative dP/dt, while a significant reduction was observed in the exponential time constant of the first 40 ms of isovolumetric relaxation (t-constant decreased from 38 +/- 8 to 34 +/- 7 ms, P less than 0.01). No changes were observed in end-diastolic and end-systolic left ventricular volume indices and ejection fraction. Thus, intravenous gallopamil induced a moderate afterload reduction and a slight negative inotropic effect resulting in a net effect of unchanged left ventricular pump function. The observed improvement of early relaxation seems to be a potentially beneficial effect of gallopamil in patients with coronary artery disease.
Pharmacokinetic and pharmacodynamic properties were studied after intravenous administration of ajmaline 1 mg/kg in an anuric patient, who underwent the electrophysiological ajmaline test. The magnitude and rate of onset of the typical electrophysiological effects of ajmaline (prolongation in atrio-Hisian and His-ventriculum conduction times) were within the range of normal values. The plasma concentration curve showed a triexponential decay with half-lives as follows: initial phase (t1/2 alpha) 1.34 min, fast elimination phase (t1/2 beta) 10.13 min and terminal (slow) phase (t1/2 gamma) 258.6 min. Other relevant pharmacokinetic parameters calculated were: total plasma clearance 45.91 L/h; volume of distribution 285.6L; protein binding 47%. Five hours after administration the patient underwent a 3.5h haemodialysis without any substantial increase in the slope of the final elimination phase of the curve. A major problem in interpreting the pharmacokinetic results is the lack of reliable reference data in healthy subjects. It is likely that the ajmaline t1/2 reported in the literature (13.4 min) does not reflect the true terminal t1/2 of the drug, because it was determined during an unduly short sampling period (30 min). Nevertheless, if we compare just the first 30 min of the concentration-time curves, our results are nearly superimposable on those found in healthy subjects.
In 25 patients undergoing diagnostic cardiac catheterization, a catheter-tip electromagnetic velocity transducer was used to evaluate maximum velocity and acceleration of blood in the ascending aorta. All patients underwent a complete haemodynamic evaluation, including high-fidelity recording of intraventricular pressures and calculation of the derived indices, left ventriculography and coronary angiography. Nineteen patients with critical coronary stenoses were divided according to the presence of signs of left ventricular dysfunction, while the control group consisted of six subjects with chest pain, but without cardiac abnormalities detectable by cardiac catheterization. Maximum aortic acceleration was significantly lower in coronary patients (378 +/- 130 vs 562 +/- 82 in the control group P less than 0.01) and also in the selected subgroup of coronary patients with normal haemodynamic and angiographic indices of left ventricular systolic function (310 +/- 102 vs 562 +/- 82, P less than 0.01). No relationship could be observed between maximal blood acceleration and left ventricular peak systolic pressure, +dP/dt, left ventricular end-systolic volume index and ejection fraction. Our results suggest that maximal blood acceleration from the left ventricle may detect an initial myocardial impairment in patients with definite coronary artery disease but with normal conventional indices of left ventricular function. The clinical interest of this index, however, is limited by overlapping values in patients with and without coronary artery disease and the inability of a further separation of ischaemic patients in accordance with the severity of left ventricular impairment and the extension of coronary artery involvement.
The acute effects of ibopamine (active ingredient of Inopamil), an orally active dopaminergic agent, were invasively evaluated in 16 consecutive patients with idiopathic dilated cardiomyopathy (New York Heart Association Functional Class II and III) Single doses of 100 and 200 mg were administered to 7 and 9 patients, respectively, and two repeated doses of 100 mg were studied in 6 patients. In order to assess the onset of cardiovascular effect, control hemodynamic measurements were repeated 5, 10, 15, 20, 30, 60, 120, and 180 min after ibopamine 200 mg. Both the tested doses of ibopamine increased the mean pulmonary arterial pressure and the mean pulmonary wedge pressure, with a maximal effect 15 min after drug ingestion (+ 47.0 and + 65.4% in the 200 mg group, p less than 0.002). Pulmonary pressures returned to baseline or lower values beyond 60 min. Systemic arterial pressure showed a small transient increase (+ 7.9% in the 200 mg group at 15 min), but fell significantly below baseline after 120 min, a larger decrease occurring in the 100 mg group (p less than 0.05). Ibopamine had a slower but more prolonged effect on cardiac output (increase of up to 32.1% at 60 min) and systemic vascular resistances. Repeated doses (100 mg after an 8-h interval) elicited comparable cardiovascular effects. Oral ibopamine caused a significant increase in mean pulmonary arterial and capillary pressures as early as 5 min after drug ingestion, before cardiac output and peripheral vascular resistances were affected. A biphasic hemodynamic response was also observed after single and repeated low (100 mg) doses of ibopamine.
symptomatic dilated cardiomyopathy were studied in order to evaluate the effect of long term sympathetic beta-blockade with metoprolol. Clinical evaluation, stress test, two-dimensional echocardiography, 24 hour ambulatory electrocardiography and hemodynamic assessment with Swan-Ganz catheter were performed before enrollment in the study. Patients were randomly assigned to the relative placebo (8 pts) or metoprolol group (12 pts) in a single-blind fashion. The placebo group received standard therapy (digitalis, diuretics, vasodilators and anticoagulants as needed), while the metoprolol group, along with standard therapy received low-dose beta-blockade, starting with 6.25 mg twice daily and then doubling every 4 days on the two daily administrations. The therapeutic end-point was 100 mg. Patients received less than 100 mg if their systolic blood pressure was less than 100 mmHg or if their resting heart rate was less than 55 beats/min. Patients were clinically assessed every month and a 24-hour electrocardiography, echocardiography and hemodynamic control was repeated after six months. In the metoprolol group there was one sudden death and two drop-outs.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the acute effects of intravenous nifedipine on hemodynamics and left ventricular function of CAD patients without previous treatment (group 1) and of 10 CAD patients receiving acebutolol (9 mg/kg daily) and who had been shown to be adequately beta blocked (reduction in heart rate by 25%) (group 2). Intravenous nifedipine (15 micrograms/kg) significantly reduced systemic peripheral resistances in both groups: this was associated with decreased systolic blood pressure and increased left ventricular cardiac output with a slight nonsignificant increase of ejection fraction. There was a significant increase in heart rate in both groups, the chronotropic response to nifedipine being attenuated in patients receiving acebutolol. Left ventricular end-diastolic pressure did not change in the first group, but it was significantly decreased in the second group, with a concomitant increase of end-diastolic left ventricular volume, suggesting an amelioration of diastolic compliance. The effect of nifedipine on intrinsic myocardial contractility was quite different, depending on the presence of beta adrenergic blockade. When given to patients of group 1, nifedipine significantly increased dP/dtmax, Vcemax, and Vmaxd. The same indices, however, were significantly depressed when nifedipine was given to the patients of group 2 receiving acebutolol. This study shows that intravenous nifedipine can be usefully administered to patients with coronary artery disease who have been on adequate beta-blocking doses of acebutolol with relative safety. Under these conditions nifedipine increases cardiac output in association with arterial dilation, despite evidence for a negative inotropic effect. These data also suggest that such an intrinsic negative inotropic effect would normally be masked by compensatory sympathetic activity.
We have evaluated the effects of nifedipine and verapamil on rate of left ventricular relaxation in 26 patients having coronary arterial disease with normal ejection fraction and normal left ventricular contractility. None of the patients had myocardial infarction. All patients showed normal contractile indices and abnormally high values of T constant, neg, dP/dt and left ventricular protodiastolic pressure, suggesting an impairment of left ventricular relaxation. Nifedipine, injected intravenously (15 micrograms/kg) in 14 patients induced a significant reduction of afterload parameters and an increase of contractility. Nifedipine also improved left ventricular relaxation, as it induced a reduction of the T constant from 42 +/- 2 msec to 33 +/- 2 msec (P less than 0.01). It induced a tendency to a reduction of negative dP/dt and protodiastolic pressure without reaching statistical significance. Verapamil, injected intravenously in the remaining 12 patients (0.1 mg/kg as a bolus followed by chronic infusion of 0.005 mg/kg/min for 3 min) induced a reduction of the T constant from 43 +/- 10 to 37 +/- 6 msec (P less than 0.01). It reduced the negativity of dP/dt from 2302 +/- 273 to 2021 +/- 252 mm Hg/sec (P less than 0.05) and of left ventricular protodiastolic pressure from 3.2 +/- 1.4 to 1.5 +/- 1.1 mm Hg (P less than 0.01). Verapamil, like nifedipine, reduced the afterload parameters although to a lesser extent. It did not substantially affect the left ventricular contractility. These data suggest that abnormalities of left ventricular relaxation may precede changes in systolic function and that nifedipine and verapamil favourably modify the indices of left ventricular diastolic function in patients with coronary arterial disease.
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It is well known that many cardiovascular drugs affect digoxin kinetics, but nothing is defined on propafenone-digoxin interaction. To clarify this problem, we studied digoxin kinetics in 8 healthy men, who received digoxin oral dose (0.50 mg) in the control state and again during maintenance therapy with propafenone (150 mg q.i.d.). Statistically significant changes were observed during propafenone in a number of digoxin kinetic indexes: a rise in peak serum digoxin concentration (4.30 vs 3.07 ng/ml - p less than 0.005), in area under the serum-digoxin concentration curve (4 h: 520.4 vs 368.9; 10 h: 789.6 vs 621.3 ng X min/ml - p less than 0.005; 24 h: 1187.6 vs 954.7 ng X min/ml - p less than 0.05) and urinary excretion of digoxin (277.7 vs 203.5 mcg - p less than 0.005). Renal digoxin clearance was not affected by propafenone. We conclude that propafenone interact kinetically with digoxin in healthy subjects, perhaps increasing digoxin bioavailability.
The aim of this study is to test left ventricular diastolic function in coronary artery disease patients with preserved systolic performance. Two groups of patients (25 coronary artery disease patients with angiographic proved coronary artery stenosis, but with normal hemodynamic and angiographic indices of systolic phase, first group; and 14 normal subjects for control, second group) were tested comparing their systolic and diastolic ventricular function indices, obtained by using a Millar microtip catheter and a computerized program. Systolic ventricular function was similar in the two groups (EF: 0.61 +/- 0.05 vs 0.62 +/- 0.03, p: n.s.; Vmax:120 +/- 28 vs 112 +/- 24 sec-1, p: n.s.), while diastolic indices were significantly different (lowest diastolic pressure: 3.7 +/- 2.4 vs -1.72 +/- 1.45 mmHg, p less than 0.01; end-diastolic pressure: 11.2 +/- 4.2 vs 6.5 +/- 2.8 mmHg, p less than 0.05; T constant: 45 +/- 8 vs 35 +/- 6 mmHg, p less than 0.001; end-diastolic compliance: 2.79 +/- 0.3 X 10(-2) vs 5.68 +/- 0.4 X 10(-2) mmHg-1, p less than 0.001; Kp: 0.041 +/- 0.006 vs 0.003 +/- 0.004 p less than 0.001). In conclusion, impairment of left ventricular diastolic phase may be one of the earliest manifestations of functional alterations of ischemic ventricle.
We determined the effects of L-carnitine on myocardial metabolism in 18 patients with angiographically-proven coronary artery disease, subjected to two rapid coronary sinus pacing evaluations. L-Carnitine converted lactate production to extraction and increased the percentage of free fatty acid extraction. These results suggest that L-carnitine may be of use to improve the metabolism of coronary artery disease patients.
The aim of the study was to assess the effect of Prenalterol on cardiovascular beta adrenergic system of 12 coronary artery disease patients with a previous myocardial infarction. For this purpose, left ventricular function was assessed before and after intravenous administration of 30 gamma/Kg of Prenalterol, under a constant heart rate, provided by atrial pacing. Prenalterol induced a significant improvement of left ventricular contractility (dp/dt pos.-VCEmax-Vmax d), relaxation (dp/dt neg.-T constant), ventricular compliance (total diastolic compliance-modulus of chamber stiffness-end-diastolic compliance) and pump (ejection fraction) indices. These results suggest the potential usefulness of Prenalterol in severe acute cardiac failure.
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